Rheumatoid ArthritisPhase 2NCT00424346
Efficacy, Safety and Tolerability of ACZ885 in Patients With Active Rheumatoid Arthritis
A Phase 2 study testing Canakinumab in people with Rheumatoid Arthritis, run by Novartis at 17 sites in 6 countries.
Trial summary
The 12-week core study was designed to evaluate risk-benefit of three subcutaneous dose regimens of ACZ885, added on to stable methotrexate (MTX) therapy (greater than or equal to 7.5 mg/week), compared to placebo in patients with active rheumatoid arthritis (RA). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Canakinumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 274 participants
- Where
- 17 sitesin 6 countries
- Study dates
- Nov 2006to Oct 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Core Study Inclusion Criteria At Screening
- Cooperative male or non-pregnant, non-lactating female patients at least 18 years of age who signed an informed consent before the initiation of any study procedure.
- Diagnosis of rheumatoid arthritis (RA) classified by American College of Rheumatology (ACR) 1987 revised criteria and with symptoms for at least 3 months before randomization.
- Functional status class I, II or III classified according to the ACR 1991 revised criteria.
- Patients treated with methotrexate (MTX) at the maximum tolerated (≤25 mg/week) and stable dose of ≥7.5 mg/week for at least 12 weeks before randomization.
- Patients who had failed any disease-modifying antirheumatic drugs (DMARDs) (including biologic agents and any DMARD used in combination with MTX) were allowed.
Show all 25Show fewer
- For patients with previous treatment of biological therapy, the following wash-out periods were required before randomization:
- 3 days for Kineret™ (anakinra) - with a terminal half-life of 4 to 6 hours (s.c. route).
- 4 weeks for Enbrel® (etanercept) - with a terminal half-life of 102 ± 30 hours (s.c.
- route).
- 8 weeks for Remicade® (infliximab) - with a terminal half-life of 8.0-9. 5 days (intravenous (i.v.) infusion).
- 12 weeks for Humira® (adalimumab) - with a terminal half-life of 10-20 days (average 2 weeks) (subcutaneous (s.c.) route).
- 12 weeks for Orencia® (abatacept) - with a terminal half-life of 13.1 (8-25) days (i.v. infusion).
- 26 weeks for any other biologic - or 10 half-lives, whichever was longer.
- Patients who took systemic corticosteroids had to be on a stable dose of ≤10 mg/d prednisone or equivalent for at least 4 weeks before randomization.
- Patients who were regularly taking non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors or paracetamol/ acetaminophen as part of their RA therapy must have been on a stable dose for at least 4 weeks before randomization. Patients taking NSAIDs or COX-2 inhibitors or paracetamol/acetaminophen as needed within 2 weeks before randomization had to stop their medication at least 24 hours before an ACR visit (i.e. Visits 3, 7, 8, 10 and 12 [End of Study]). Patients taking folic acid supplementation had to be on stable dose for at least 4 weeks before randomization.
- Patients with a history of immunization for Influenza (within past 12 months) and Pneumococcal vaccination (within 4 years) were included. If not already immunized, vaccination was completed when medically indicated (only during flu season for influenza) and such patients were included after approximately a 3 week window post-immunization to allow immunity to develop for vaccine.
- Weight ≥45 kg and body mass index (BMI) <34.0
- Women of non-child-bearing potential, defined as all women physiologically not capable of becoming pregnant.
- Core Study Inclusion criteria At Baseline (Visit 3)
- Disease activity criteria of ≥6 out of 28 tender joints and ≥6 out of 28 swollen joints.
- One of the following also had to be present:
- High-sensitive C-Reactive Protein (hsCRP) concentration ≥10 mg/L
- Erythrocyte Sedimentation Rate (ESR) ≥28 mm/1st hr
- a. + b. based on screening values.
Who cannot join
- History of hypersensitivity to study drug or to molecules with similar structures.
- Any therapy by intra-articular injections (e.g. corticosteroid) required for treatment of acute RA flare within 4 weeks before randomization.
- Current use of DMARDs other than MTX. DMARDs included but were not limited to: biologic agents, thiolates (D-penicillamine, thiopronine), sulfasalazine, gold compounds, antimalarials, cyclosporine A, azathioprine, leflunomide, and alkylating agents such as cyclophosphamide.
- If a patient had been discontinued from DMARDs, the patient should have been off the agent for at least 4 weeks, except leflunomide which was 8 weeks.
- Patients with evidence of active pulmonary disease (e.g. tuberculosis, fungal diseases).
- Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.
Show all 24Show fewer
- Who had a live vaccination within 12 weeks before randomization, or were planning to have one during the study and were not willing/able to postpone until study completion.
- a) With bacterial, fungal or viral infections at the time of enrollment, including patients with evidence of human immunodeficiency virus (HIV) infection, hepatitis B and hepatitis C infection.
- History of a positive purified protein derivative (PPD) of tuberculin skin test without a follow-up of a negative chest X-ray.
- Patients requiring administration of antibiotics against latent tuberculosis, e.g. isoniazide.
- Underlying metabolic, hematologic, renal, hepatic, infectious or gastrointestinal conditions which in the opinion of the investigator immunocompromised the patient and/or placed the patient at unacceptable risk for participation in an immunomodulatory therapy. In particular, clinical evidence or history of multiple sclerosis or other demyelinating diseases, or Felty's syndrome.
- With significant medical problems, including but not limited to the following: uncontrolled hypertension (≥160/95 mmHg), congestive heart failure, type-I-diabetes(well controlled type-II-diabetes was allowed even when requiring insulin), thyroid disease (unless the patient was taking a stable dose of thyroid hormone for at least 12 weeks before randomization).
- Other rheumatic diseases that could confound the evaluation of efficacy, including but not limited to primary fibromyalgia, ankylosing spondylitis, Lyme disease, adult juvenile RA, systemic lupus erythematosus, gout and pseudo gout, vasculitis, psoriatic arthritis, reactive arthritis, primary Sjoegren's Syndrome, and Behcet's Syndrome.
- Any medical or psychiatric condition which, in the Investigator's opinion, would preclude the participant from adhering to the protocol or completing the study per protocol.
- History of malignancy of any organ system, treated or untreated, within the past 5 years (with the exception of adequately treated basal cell carcinoma or squamous-cell carcinoma of the skin, carcinoma in situ of the cervix, colon polyps with non-invasive malignancy that have been removed).
- Use of any investigational drug other than RA therapy and/or devices at the time of randomization, or within 30 days or 5 half- lives of randomization, whichever was longer.
- STUDY EXTENSIONS
- Extension Studies Inclusion Criteria:
- Patients who completed the core CACZ885A2201 study may enter the first extension study upon signing informed consent. A patient is defined as completing the study if he/she completed the core CACZ885A2201 study up to and including Visit 12.
- Patients who completed the first extension study, may enter the second.
- Extension Studies Exclusion Criteria
- Patients for whom continued treatment in the extension is not considered appropriate by the treating physician.
- Patients who were non-compliant or who demonstrated a major protocol violation in the core CACZ885A2201 study.
- Patients who discontinued from the core CACZ885A2201 study before Visit 12.
Trial locations and contacts
17 sites in 6 countries.
17 sites in 6 countries
United States12 sites
The Center for Rheumatology
Albany, New York, 12206
Pinnacle Research Group
Anniston, Alabama, 36207
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Arthritis Center
Palm Harbor, Florida, 34684
Arthritis Research of Florida, Inc.
Palm Harbor, Florida, 34684
Sun Valley Arthritis Center, Ltd
Peoria, Arizona, 85381
Oregon Health Sciences University
Portland, Oregon, 97239
AAIR Research Center
Rochester, New York, 14618
The Arthritis Center
Springfield, Illinois, 62704
St. Louis Cener for Clinical Research
St Louis, Missouri, 63128
Tacoma Center for Arthritis Research
Tacoma, Washington, 98405
Catalina Pointe Arthritis & Rheumatology Specialists
Tucson, Arizona, 85704
About this study
Official title: A 12-week, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Dose-finding Study to Evaluate the Efficacy, Safety and Tolerability of ACZ885 (Anti-interleukin-1beta Monoclonal Antibody) With Three Different Dose Regimens in Patients With Active Rheumatoid Arthritis Despite Stable Treatment With Methotrexate Including 76-week and 96-week Extensions
The 12-week core study was designed to evaluate risk-benefit of three subcutaneous dose regimens of ACZ885, added on to stable methotrexate (MTX) therapy (greater than or equal to 7.5 mg/week), compared to placebo in patients with active rheumatoid arthritis (RA). The study investigated the magnitude of effect as well as onset of effect for the different dose regimens.
The primary objective of the extension studies was to assess long-term safety and tolerability of canakinumab (ACZ885) in patients with active RA. CACZ885A2201E1 evaluated this objective in patients who had participated in the core study (CACZ885A2201) and CACZ885A2201E2 did the same in patients who completed the first extension study.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Canakinumab, Placebo
- Keywords
- Active Rheumatoid Arthritis, anti-interleukin-1beta monoclonal antibody, methotrexate
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CanakinumabDrug
Also called ACZ885
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Experimental | Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks. Receives: Drug: Canakinumab |
| Canakinumab 300 mg q2wk | Experimental | Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks. Receives: Drug: Canakinumab |
| Canakinumab 150 mg q4wk | Experimental | Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks. Receives: Drug: Canakinumab |
| Placebo | Placebo comparator | Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Week 12
Participants were defined as ACR50 responders if they had at least a 50% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures:
- Patient's pain assessment (assessed using a 100 mm Visual Analog Scale [VAS]);
- Patient's global assessment of disease activity (VAS 100 mm);
- Physician's global assessment of disease activity (VAS 100 mm);
- Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score);
- Acute phase reactant (high sensitivity C-reactive Protein [hsCRP]).
Details on each of these components are provided in Outcome Measures 10-16. Participants were considered as non-responders if they failed the ACR50 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.
Measured: Baseline and Week 12
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase
Participants were defined as ACR20 responders if they had at least a 20% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures:
- Patient's pain assessment (assessed using a 100 mm Visual Analog Scale [VAS])
- Patient's global assessment of disease activity (VAS 100 mm)
- Physician's global assessment of disease activity (VAS 100 mm)
- Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score)
- Acute phase reactant (high sensitivity C-reactive Protein [hsCRP]).
Participants were considered as non-responders if they failed the ACR20 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.
Measured: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase
Participants were defined as ACR50 responders if they had at least a 50% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures:
- Patient's pain assessment (assessed using a 100 mm Visual Analog Scale [VAS])
- Patient's global assessment of disease activity (VAS 100 mm)
- Physician's global assessment of disease activity (VAS 100 mm)
- Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score)
- Acute phase reactant (high sensitivity C-reactive Protein [hsCRP]).
Participants were considered as non-responders if they failed the ACR50 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.
Measured: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase
Participants were defined as ACR70 responders if they had at least a 70% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures:
- Patient's pain assessment (assessed using a 100 mm Visual Analog Scale [VAS])
- Patient's global assessment of disease activity (VAS 100 mm)
- Physician's global assessment of disease activity (VAS 100 mm)
- Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score)
- Acute phase reactant (high sensitivity C-reactive Protein [hsCRP]).
Participants were considered as non-responders if they failed the ACR70 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.
Measured: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124
Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase
The Disease Activity Score (DAS) 28 is a combined index to measure the disease activity in patients with rheumatoid arthritis, and includes the following variables:
- The number of swollen and tender joints assessed using the 28-joint count;
- C-reactive protein (CRP) in mg/L;
- Patient's global assessment of disease activity measured on a 100 mm visual analog scale.
The DAS28 score ranges from zero to ten. DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6
Measured: Baseline and Weeks 24, 72 and 112
Secondary outcomes (25)
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8
Participants were defined as ACR50 responders if they had at least a 50% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures:
- Patient's pain assessment (assessed using a 100 mm Visual Analog Scale [VAS]);
- Patient's global assessment of disease activity (VAS 100 mm);
- Physician's global assessment of disease activity (VAS 100 mm);
- Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score);
- Acute phase reactant (high sensitivity C-reactive Protein [hsCRP]).
Participants were considered as non-responders if they failed the ACR50 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.
Measured: Baseline and Weeks 2, 4 and 8
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders
Participants were defined as ACR20 responders if they had at least a 20% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures:
- Patient's pain assessment (assessed using a 100 mm Visual Analog Scale [VAS]);
- Patient's global assessment of disease activity (VAS 100 mm);
- Physician's global assessment of disease activity (VAS 100 mm);
- Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score);
- Acute phase reactant (high sensitivity C-reactive Protein [hsCRP]).
Participants were considered ACR20 non-responders if they failed the ACR20 criteria. Patients who prematurely discontinued the study due to insufficient therapeutic effect were also considered non responders.
Measured: Baseline and Weeks 2, 4, 8 and 12
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders
Participants were defined as ACR70 responders if they had at least a 70% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures:
- Patient's pain assessment (assessed using a 100 mm Visual Analog Scale [VAS]);
- Patient's global assessment of disease activity (VAS 100 mm);
- Physician's global assessment of disease activity (VAS 100 mm);
- Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score);
- Acute phase reactant (high sensitivity C-reactive Protein [hsCRP]).
Participants were considered ACR70 non-responders if they failed the ACR70 criteria. Patients who prematurely discontinued the study due to insufficient therapeutic effect were also considered non responders.
Measured: Baseline and Weeks 2, 4, 8 and 12
Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12
To assess differences between the level of clinical response attained and not just whether the patient did or did not achieve a particular level of response, participants were categorized as follows:
- Did not attain an ACR20 response;
- Attained a 20% but not a 50% response;
- Attained a 50% but not a 70% response;
- Attained a 70% or greater response.
A participant was considered as improved according to the ACR20, ACR50 or ACR70 criteria if they had at least a 20, 50 or 70% improvement from Baseline, respectively, in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures:
- Patient's pain assessment (100 mm visual analog scale [VAS]);
- Patient's global assessment of disease activity (VAS 100 mm);
- Physician's global assessment of disease activity (VAS 100 mm);
- Patient self-assessed disability (Health Assessment Questionnaire [HAQ] score);
- Acute phase reactant (high sensitivity C-reactive Protein [hsCRP]).
Measured: Baseline and Week 12
Change From Baseline in Swollen 28-joint Count
The following 28 joints were assessed by the physician for swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2).
Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.
Measured: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Tender 28-joint Count
The following 28 joints were assessed by the physician for tenderness: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2).
Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.
Measured: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Patient's Pain Intensity
The patient's assessment of pain was performed using a 100 mm visual analog scale (VAS) ranging from no pain (0) to unbearable pain (100). The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in pain intensity.
Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.
Measured: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Patient's Global Assessment of Disease Activity
The patient's global assessment of disease activity was performed using a 100 mm visual analog scale (VAS) ranging from no arthritis activity (0) to maximal arthritis activity (100), after the question "Considering all the ways your arthritis affects you, draw a line on the scale for how well you are doing". The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in assessment of disease activity.
Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.
Measured: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Physician's Global Assessment of Disease Activity
The physician's global assessment of disease activity was performed using a 100 mm visual analog scale (VAS) ranging from no arthritis activity (0) to maximal arthritis activity (100). To enhance objectivity, the physician was not aware of the specific patient's global assessment of disease activity when performing their own assessment on that patient. The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in assessment of disease activity.
Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.
Measured: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Health Assessment Questionnaire (HAQ) Score
The patient health assessment questionnaire (HAQ) was used to assess the physical ability and functional status of participants as well as quality of life. The disability dimension consists of 20 multiple choice items concerning difficulty in performing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from four response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A negative change from Baseline score indicates improvement in disability status.
Least squares means (LSM) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.
Measured: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels
HsCRP is a marker for inflammation and was measured from blood samples to identify the presence of inflammation, to determine its severity, and to monitor response to treatment.
Least squares means (LSMs) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline value as a covariate.
Measured: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Disease Activity Score (DAS) 28
The Disease Activity Score (DAS) 28 is a combined index to measure the disease activity in patients with rheumatoid arthritis, and includes the following variables:
- The number of swollen and tender joints assessed using the 28-joint count;
- C-reactive protein (CRP) in mg/L;
- Patient's global assessment of disease activity measured on a 100 mm visual analog scale.
The DAS28 score ranges from zero to ten. DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6.
Least squares means (LSMs) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline DAS28 value as a covariate.
Measured: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Erythrocyte Sedimentation Rate
Erythrocyte sedimentation rate (ESR) indirectly measures how much inflammation is in the body. A higher ESR is indicative of increased inflammation. A negative change from Baseline score indicates improvement.
Measured: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Rheumatoid Factor Concentration
Rheumatoid factor (RF) is an autoantibody (antibody directed against an organism's own tissues) that is an indicator of inflammation and rheumatoid arthritis.
Measured: Baseline and Weeks 4, 8 and 12
Change From Baseline in Short Form 36 Health Survey (SF-36)
The SF-36 measures the impact of disease on overall quality of life and consists of eight subscales (physical function, pain, general and mental health, vitality, social function, physical and emotional health) which can be aggregated to derive a physical-component summary score and a mental-component summary score. Scores for each subscale range from 0 to 10, and the composite scores range from 0 to 100, with higher scores indicating better health. A positive change from Baseline score indicates improvement in quality of life.
Measured: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F)
The fatigue subscale of the FACIT is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Participants respond to each item on a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much) based on their experience of fatigue during the past 2 weeks. The scale score is computed by summing the item scores, after reversing those items that are worded in the negative direction. FACIT Fatigue subscale scores range from 0 to 52, where higher scores represent less fatigue.
Least squares means (LSMs) were derived from an Analysis of Covariance (ANCOVA) model adjusting for treatment and center with baseline FACIT-F value as a covariate.
Measured: Baseline and Weeks 2, 4, 8 and 12
Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study
To assess differences between the level of clinical response attained and not just whether the patient did or did not achieve a particular level of response, patients were categorized as follows:
- Did not attain an ACR20 response;
- Attained a 20% but not a 50% response;
- Attained a 50% but not a 70% response;
- Attained a 70% or greater response.
A participant was considered as improved according to the ACR20, ACR50 or ACR70 criteria if they had at least a 20, 50 or 70% improvement from Baseline, respectively, in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures:
- Patient's pain assessment (100 mm visual analog scale [VAS]);
- Patient's global assessment of disease activity (VAS 100 mm);
- Physician's global assessment of disease activity (VAS 100 mm);
- Patient self-assessed disability (Health Assessment Questionnaire [HAQ] score);
- Acute phase reactant (high sensitivity C-reactive Protein [hsCRP]).
Measured: Baseline and End of Study (up to 124 weeks)
Change From Baseline in Swollen 28-joint Count During the Extension Study
The following 28 joints were assessed by the physician for swelling: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2).
Measured: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Change From Baseline in Tender 28-joint Count During the Extension Study
The following 28 joints were assessed by the physician for tenderness: metacarpophalangeal I-V (10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), shoulders (2), and knees (2).
Measured: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Change From Baseline in Patient's Pain Intensity During the Extension Study
The patient's assessment of pain was performed using a 100 mm visual analog scale (VAS) ranging from no pain (0) to unbearable pain (100). The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in pain intensity.
Measured: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study
The patient's global assessment of disease activity was performed using a 100 mm visual analog scale (VAS) ranging from no arthritis activity (0) to maximal arthritis activity (100), after the question "Considering all the ways your arthritis affects you, draw a line on the scale for how well you are doing". The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in assessment of disease activity.
Measured: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study
The physician's global assessment of disease activity was performed using a 100 mm visual analog scale (VAS) ranging from no arthritis activity (0) to maximal arthritis activity (100). To enhance objectivity, the physician was not aware of the specific patient's global assessment of disease activity when performing their own assessment on that patient. The distance in mm from the left edge of the scale was measured. A negative change from Baseline score indicates improvement in assessment of disease activity.
Measured: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study
The patient health assessment questionnaire (HAQ) was used to assess the physical ability and functional status of participants as well as quality of life. The disability dimension consists of 20 multiple choice items concerning difficulty in performing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from four response categories, ranging from 'without any difficulty' (Score=0) to 'unable to do' (Score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A negative change from Baseline score indicates improvement in disability status.
Measured: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study
HsCRP is a marker for inflammation and was measured from blood samples to identify the presence of inflammation, to determine its severity, and to monitor response to treatment.
Measured: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study
Erythrocyte sedimentation rate (ESR) indirectly measures how much inflammation is in the body. A higher ESR is indicative of increased inflammation. A negative change from Baseline score indicates improvement.
Measured: Baseline and Weeks 24, 36, 48, 60, 72 and 88.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2007 (estimated)
- Study startNov 2006
- Primary completionSep 2008
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 274 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00424346
- Sponsor's protocol ID
- CACZ885A2201
- Other IDs
- CACZ885A2201E1, CACZ885A2201E2
- Status last verified
- Jun 2013
- First submitted
- 17 Jan 2007
- Last updated
- 10 Feb 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Alten R, Gomez-Reino J, Durez P, Beaulieu A, Sebba A, Krammer G, Preiss R, Arulmani U, Widmer A, Gitton X, Kellner H. Efficacy and safety of the human anti-IL-1beta monoclonal antibody canakinumab in rheumatoid arthritis: results of a 12-week, Phase II, dose-finding study. BMC Musculoskelet Disord. 2011 Jul 7;12:153. doi: 10.1186/1471-2474-12-153.
PubMed 21736751
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 12-week, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Dose-finding Study to Evaluate the Efficacy, Safety and Tolerability of ACZ885 (Anti-interleukin-1beta Monoclonal Antibody) With Three Different Dose Regimens in Patients With Active Rheumatoid Arthritis Despite Stable Treatment With Methotrexate Including 76-week and 96-week Extensions
- ClinicalTrials.gov ID
- NCT00424346
- Acronym / sponsor ID
- CACZ885A2201
- Conditions
- Rheumatoid Arthritis
- Keywords
- Active Rheumatoid Arthritis, anti-interleukin-1beta monoclonal antibody, methotrexate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 274 participants (actual)
- Lead sponsor
- NovartisIndustry (pharma, biotech, devices)
- Study start
- Nov 2006
- Primary completion
- Sep 2008 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 19 Jan 2007 (estimated)
- Results
- Posted 19 Jun 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The 12-week core study was designed to evaluate risk-benefit of three subcutaneous dose regimens of ACZ885, added on to stable methotrexate (MTX) therapy (greater than or equal to 7.5 mg/week), compared to placebo in patients with active rheumatoid arthritis (RA). The study investigated the magnitude of effect as well as onset of effect for the different dose regimens.
The primary objective of the extension studies was to assess long-term safety and tolerability of canakinumab (ACZ885) in patients with active RA. CACZ885A2201E1 evaluated this objective in patients who had participated in the core study (CACZ885A2201) and CACZ885A2201E2 did the same in patients who completed the first extension study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Canakinumab 600 mg IV + 300 mg q2wk | Experimental | Drug: CanakinumabParticipants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks. |
| Canakinumab 300 mg q2wk | Experimental | Drug: CanakinumabParticipants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks. |
| Canakinumab 150 mg q4wk | Experimental | Drug: CanakinumabParticipants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Core Study Inclusion Criteria At Screening
- Cooperative male or non-pregnant, non-lactating female patients at least 18 years of age who signed an informed consent before the initiation of any study procedure.
- Diagnosis of rheumatoid arthritis (RA) classified by American College of Rheumatology (ACR) 1987 revised criteria and with symptoms for at least 3 months before randomization.
- Functional status class I, II or III classified according to the ACR 1991 revised criteria.
- Patients treated with methotrexate (MTX) at the maximum tolerated (≤25 mg/week) and stable dose of ≥7.5 mg/week for at least 12 weeks before randomization.
Key exclusion criteria (24 listed)
- History of hypersensitivity to study drug or to molecules with similar structures.
- Any therapy by intra-articular injections (e.g. corticosteroid) required for treatment of acute RA flare within 4 weeks before randomization.
- Current use of DMARDs other than MTX. DMARDs included but were not limited to: biologic agents, thiolates (D-penicillamine, thiopronine), sulfasalazine, gold compounds, antimalarials, cyclosporine A, azathioprine, leflunomide, and alkylating agents such as cyclophosphamide.
- If a patient had been discontinued from DMARDs, the patient should have been off the agent for at least 4 weeks, except leflunomide which was 8 weeks.
- Patients with evidence of active pulmonary disease (e.g. tuberculosis, fungal diseases).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CanakinumabAlso: ACZ885 | Drug | Canakinumab 150 mg q4wk, Canakinumab 300 mg q2wk, Canakinumab 600 mg IV + 300 mg q2wk |
| Placebo | Drug | Placebo |
Primary outcome
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Week 12
Time frame: Baseline and Week 12
Participants were defined as ACR50 responders if they had at least a 50% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale [VAS]); * Patient's global assessment of disease activity (VAS 100 mm); * Physician's global assessment of disease activity (VAS 100 mm); * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score); * Acute phase reactant (high sensitivity C-reactive Protein [hsCRP]). Details on each of these components are provided in Outcome Measures 10-16. Participants were considered as non-responders if they failed the ACR50 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124
Participants were defined as ACR20 responders if they had at least a 20% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale [VAS]) * Patient's global assessment of disease activity (VAS 100 mm) * Physician's global assessment of disease activity (VAS 100 mm) * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) * Acute phase reactant (high sensitivity C-reactive Protein [hsCRP]). Participants were considered as non-responders if they failed the ACR20 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124
Participants were defined as ACR50 responders if they had at least a 50% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale [VAS]) * Patient's global assessment of disease activity (VAS 100 mm) * Physician's global assessment of disease activity (VAS 100 mm) * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) * Acute phase reactant (high sensitivity C-reactive Protein [hsCRP]). Participants were considered as non-responders if they failed the ACR50 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124
Participants were defined as ACR70 responders if they had at least a 70% improvement from Baseline in both the tender and the swollen 28-joint count, and in at least 3 of the following 5 measures: * Patient's pain assessment (assessed using a 100 mm Visual Analog Scale [VAS]) * Patient's global assessment of disease activity (VAS 100 mm) * Physician's global assessment of disease activity (VAS 100 mm) * Patient self-assessed disability (Health Assessment Questionnaire (HAQ) score) * Acute phase reactant (high sensitivity C-reactive Protein [hsCRP]). Participants were considered as non-responders if they failed the ACR70 criteria. Participants who prematurely discontinued due to insufficient therapeutic effect were also considered non-responders.
Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase
Time frame: Baseline and Weeks 24, 72 and 112
The Disease Activity Score (DAS) 28 is a combined index to measure the disease activity in patients with rheumatoid arthritis, and includes the following variables: * The number of swollen and tender joints assessed using the 28-joint count; * C-reactive protein (CRP) in mg/L; * Patient's global assessment of disease activity measured on a 100 mm visual analog scale. The DAS28 score ranges from zero to ten. DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6
25 secondary outcomes
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8
Time frame: Baseline and Weeks 2, 4 and 8
Percentage of American College of Rheumatology [ACR] 20 Criteria Responders
Time frame: Baseline and Weeks 2, 4, 8 and 12
Percentage of American College of Rheumatology [ACR] 70 Criteria Responders
Time frame: Baseline and Weeks 2, 4, 8 and 12
Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12
Time frame: Baseline and Week 12
Change From Baseline in Swollen 28-joint Count
Time frame: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Tender 28-joint Count
Time frame: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Patient's Pain Intensity
Time frame: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Patient's Global Assessment of Disease Activity
Time frame: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Physician's Global Assessment of Disease Activity
Time frame: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Health Assessment Questionnaire (HAQ) Score
Time frame: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels
Time frame: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Disease Activity Score (DAS) 28
Time frame: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Erythrocyte Sedimentation Rate
Time frame: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Rheumatoid Factor Concentration
Time frame: Baseline and Weeks 4, 8 and 12
Change From Baseline in Short Form 36 Health Survey (SF-36)
Time frame: Baseline and Weeks 2, 4, 8 and 12
Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F)
Time frame: Baseline and Weeks 2, 4, 8 and 12
Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study
Time frame: Baseline and End of Study (up to 124 weeks)
Change From Baseline in Swollen 28-joint Count During the Extension Study
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Change From Baseline in Tender 28-joint Count During the Extension Study
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Change From Baseline in Patient's Pain Intensity During the Extension Study
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study
Time frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124.
Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study
Time frame: Baseline and Weeks 24, 36, 48, 60, 72 and 88.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21736751Alten R, Gomez-Reino J, Durez P, Beaulieu A, Sebba A, Krammer G, Preiss R, Arulmani U, Widmer A, Gitton X, Kellner H. Efficacy and safety of the human anti-IL-1beta monoclonal antibody canakinumab in rheumatoid arthritis: results of a 12-week, Phase II, dose-finding study. BMC Musculoskelet Disord. 2011 Jul 7;12:153. doi: 10.1186/1471-2474-12-153.
Related trials for Rheumatoid Arthritis
RecruitingPhase 2
Study of PTC844 in Participants With Active Rheumatoid Arthritis
Rheumatoid Arthritis
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis and Systemic Lupus Erythematosus
Not yet recruitingPhase 1
R-2487 in Patients With Sjogren's Syndrome (SjD)
Sjogren's Syndrome, Sjögren
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
17 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Canakinumab in people with Rheumatoid Arthritis, run by Novartis at 17 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Austria, Belgium, Canada, Germany and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Week 12 (time frame: Baseline and Week 12). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00424346, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2014.