Rheumatoid ArthritisPhase 3NCT02046616
A Study of Subcutaneous (SC) Tocilizumab (RoActemra/Actemra) in Participants With Active Rheumatoid Arthritis (RA) and Inadequate Response to Disease-Modifying Anti-Rheumatic Drugs (DMARDs)
A Phase 3 study testing Tocilizumab, Methotrexate and Non-Biologic DMARDs in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 27 sites in 4 countries.
Trial summary
This Phase IIIb, open-label, single-arm study will evaluate the safety, efficacy, and tolerability of SC tocilizumab (RoActemra/Actemra) in monotherapy or in combination with methotrexate or other non-biologic DMARDs in participants with active RA who are naive to tocilizumab. 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?
- Tocilizumab, Methotrexate and Non-Biologic DMARDs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 133 participants
- Where
- 27 sitesin 4 countries
- Study dates
- 28 May 2014to 13 Sep 2016
- Phase
- Phase 3
- 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
- Active RA according to the revised ACR (1987) criteria or EULAR/ACR (2010) criteria
- Moderate to severe RA with a DAS28-ESR score >3.2 points
- Inadequate response and/or intolerance to MTX or other non-biologic DMARDs and/or where MTX or other non-biologic DMARDs are inappropriate
- Oral corticosteroids (less than or equal to [</=] 10 mg per day prednisolone or equivalent) and nonsteroidal anti-inflammatory drugs (NSAIDs) permitted if on stable dose regimen for greater than or equal to [>/=] 4 weeks prior to baseline
- Permitted non-biologic DMARDs allowed if at stable dose for >/=4 weeks prior to baseline
- Receiving treatment on an outpatient basis, not including tocilizumab
- Agreement to use reliable means of contraception as defined by protocol, among females of childbearing potential and males with female partners of childbearing potential
Who cannot join
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline
- Rheumatic autoimmune disease other than RA
- Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
- Diagnosis of juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16
- Prior history of or current inflammatory joint disease other than RA
- Exposure to tocilizumab or any other biologic DMARDs at any time prior to baseline
Show all 18Show fewer
- Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening
- Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
- History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
- Evidence of serious concomitant disease or disorder
- Known active current or history of recurrent infection
- Any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening
- Active tuberculosis requiring treatment within the previous 3 years
- Positive for hepatitis B or hepatitis C
- History of or current active primary or secondary immunodeficiency
- Pregnant or lactating women
- Neuropathies or other conditions that might interfere with pain evaluation
- Inadequate hematologic, renal, or liver function
Trial locations and contacts
27 sites in 4 countries.
27 sites in 4 countries
Sweden9 sites
Länssjukhuset Ryhov; Ortoped- och Reumatolog kliniken
Jönköping, 551 85
Uni Hospital Linkoeping; Dept. of Rheumatology
Linköping, 58185
Skånes Universitetssjukhus Lund; Reumatologkliniken
Lund, 221 85
Skånes Universitetssjukhus Malmö; Reumatologkliniken
Malmö, 205 02
Örebro Uni Hospital; Rheumatology
Örebro, 70185
Simrishamns Sjukhus
Simrishamn, 272 81
Karolinska Sjukhuset; Reumatologkliniken D2-1
Stockholm, 171 76
Akademiska sjukhuset, Reumatologkliniken
Uppsala, 75185
Västmanlands sjukhus Västerås, Reumatologkliniken
Västerås, 72189
Denmark7 sites
Aalborg Universitetshospital Nord, Reumatologisk Afdeling
Aalborg, 9000
Glostrup Hospital, Reumatologisk Afdeling, Ambulatoriet
Glostrup Municipality, 2600
Gentofte Hospital, Medicinsk Afd. C, Klinik for Gigt- og Rygsygdomme
Hellerup, 2900
Holbæk Sygehus, Medicinsk Afd., Reumatologisk Amb.15-2
Holbæk, 4300
Sjællands Universitetshospital, Køge; Reumatologisk Afdeling
Køge, 4600
Odense Universitetshospital, Reumatologisk Afdeling C, Ambulatoriet
Odense, 5000
Svendborg Sygehus, Reumatologisk Ambulatorium
Svendborg, 5700
Finland6 sites
Helsinki University Central Hospital; Rheumatology Clinic
Helsinki, 00290
Kiljavan Lääketutkimus Oy
Hyvinkää, 05800
Central Hospital of Pohjois-Karjala; Outpatient Clinic of Rheumatology
Joensuu, 80210
Keski-Suomen Keskussairaala; Sisätautien Klinikka
Jyväskylä, 40620
Lappeenranta Central Hospital; Outpatient Clinic of Internal Medicine
Lappeenranta, 53130
Oulu University Hospital; Rheumatology
Oulu, 90220
Norway5 sites
Ålesund Sykehus; Revmatologisk Avdeling
Ålesund, 6017
Haukeland Universitetssykehus; Revmatologisk Avdeling
Bergen, 5053
Drammen sykehus Vestre Viken HF, Revmatologisk avd.
Drammen, 3004
Diakonhjemmet; Reumatolgisk Avdeling
Oslo, 0370
St. Olavs Hospital; Revmatologisk avdeling
Trondheim, 7030
About this study
Official title: Tocilizumab SC in Patients With Active Rheumatoid Arthritis and Inadequate Response to DMARDs. A Single-Arm, Open-Label Study to Evaluate Safety, Tolerability and Efficacy. In a Subgroup of Patients Inflammation Will Be Measured by Ultrasound.
This Phase IIIb, open-label, single-arm study will evaluate the safety, efficacy, and tolerability of SC tocilizumab (RoActemra/Actemra) in monotherapy or in combination with methotrexate or other non-biologic DMARDs in participants with active RA who are naive to tocilizumab. Participants will receive tocilizumab 162 milligrams (mg) subcutaneously weekly (QW) for 24 weeks.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Tocilizumab, Methotrexate, Non-Biologic DMARDs
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
Also called RoActemra, Actemra
Tocilizumab 162 mg will be administered subcutaneously QW.
MethotrexateDrug
Methotrexate dosing is not specified by the protocol and will be given as per standard practice. Participants must be at a stable dose that was initiated at least 4 weeks prior to baseline.
Non-Biologic DMARDsDrug
Participants will receive non-biologic DMARDs (same non-biologic DMARD that participant was receiving at time of study entry). Dosing is not specified by the protocol and will be given as per standard practice. Participants must be at a stable dose that was initiated at least 4 weeks prior to baseline.
| Study group | Role | What they receive |
|---|---|---|
| Tocilizumab Alone or Combined with Methotrexate or Other DMARD | Experimental | All participants will receive tocilizumab as a single fixed dose (monotherapy) or in combination with methotrexate or other non-biologic DMARDs, irrespective of body weight, for 24 weeks. Receives: Drug: Tocilizumab; Drug: Methotrexate; Drug: Non-Biologic DMARDs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12
CDAI was derived as the sum of the following: tender joint count (TJC), swollen joint count (SJC), participant global assessment (PGA) of disease activity, and physician assessment of disease activity. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA and physician assessment of disease activity were scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity. The total CDAI score range was 0-76, where higher scores indicate increased disease activity. Change from baseline was averaged among all participants. Negative values indicate improvement/reduction in RA disease activity.
Measured: Baseline, Week 12
Secondary outcomes (16)
Change From Baseline in Disease Activity Score 28 (DAS28)-Erythrocyte Sedimentation Rate (ESR) Score
DAS28-ESR was based on TJC, SJC, PGA of disease activity, and laboratory-derived ESR. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA of disease activity was scored 0-100 mm on a VAS, where higher scores indicate greater perceived disease activity. The total DAS28-ESR score was transformed to a single score range of 0-10, where higher scores indicate increased disease activity. Change from baseline was averaged among all participants. Negative values indicate improvement/reduction in RA disease activity.
Measured: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
Percentage of Participants With American College of Rheumatology (ACR) Response
ACR response was assessed on the basis of percent improvement (20% for ACR20, 50% for ACR50, 70% for ACR70) in both TJC and SJC as well as at least three of the following: physician assessment of disease activity, PGA of disease activity, PGA of pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), and either ESR or C-reactive protein level. TJC and SJC were taken as the number of tender and swollen joints, out of 68 and 66 assessed joints, respectively. PGA and physician assessments were scored 0-100 mm on a VAS, where higher scores indicate greater perceived disease activity or pain. HAQ-DI was scored using participant responses to 20 questions assessing activities of daily living (ADLs), with total score scale of 0-3, where higher scores indicate increased functional disability. The percentage of participants meeting criteria for each level of ACR response was reported.
Measured: Weeks 2, 4, 8, 12, 16, 20, 24
Percentage of Participants With European League Against Rheumatism (EULAR) Response
EULAR response was assessed by change from baseline and absolute DAS28-ESR score. EULAR response classification was as follows: Good (change >1.2 with absolute score </=3.2), Moderate (change >1.2 with absolute score >3.2 or change >0.6 with absolute score </=5.1), None (change </=0.6 or absolute score >5.1). DAS28-ESR was based on TJC, SJC, and PGA of disease activity, and laboratory-derived ESR. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA of disease activity was scored 0-100 mm on a VAS, where higher scores indicate greater perceived disease activity. The total DAS28-ESR score was transformed to a single score range of 0-10, where higher scores indicate increased disease activity. The percentage of participants meeting criteria for each level of EULAR response was reported.
Measured: Weeks 2, 4, 8, 12, 16, 20, 24
Change From Baseline in CDAI at Weeks 2, 4, 8, 16, 20, and 24
CDAI was derived as the sum of the following: TJC, SJC, PGA of disease activity, and physician assessment of disease activity. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA and physician assessment of disease activity were scored 0-100 mm and rounded to the nearest cm on a VAS, where higher scores indicate greater perceived disease activity. The total CDAI score range was 0-76, where higher scores indicate increased disease activity. Change from baseline was averaged among all participants. Negative values indicate improvement/reduction in RA disease activity.
Measured: Baseline and Weeks 2, 4, 8, 16, 20, 24
Change From Baseline in Simplified Disease Activity Index (SDAI)
SDAI was derived as the sum of the following: TJC, SJC, PGA of disease activity, physician assessment of disease activity, and laboratory-derived C-reactive protein level. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA and physician assessment of disease activity were scored 0-100 mm and rounded to the nearest cm on a VAS, where higher scores indicate greater perceived disease activity. The total SDAI score range was 0-86, where higher scores indicate increased disease activity. Change from baseline was averaged among all participants. Negative values indicate improvement/reduction in RA disease activity.
Measured: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
Change From Baseline in TJC
TJC was taken as the number of tender joints out of 28 assessed joints.
Measured: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
Change From Baseline in SJC
SJC was taken as the number of swollen joints out of 28 assessed joints.
Measured: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
Percentage of Participants With At Least One Adverse Event Leading to Dosage Modification
The percentage of participants with at least one adverse event leading to dose/frequency reduction or temporary dose hold was reported.
Measured: Baseline up to Week 24
Number of Participants With Neutralizing Anti-Tocilizumab Antibodies
Participants were evaluated for the presence of anti-tocilizumab antibodies. Confirmatory assays were performed in the case of a positive screen assay result.
Measured: Baseline to FU Week 8 (up to 32 weeks overall)
Tocilizumab Concentration
Tocilizumab concentration was determined, averaged among all participants, and expressed in micrograms per milliliter (mcg/mL).
Measured: Predose (30 minutes) at baseline; Weeks 12, 24; and FU Week 8 (up to 32 weeks overall)
Soluble Interleukin-6 Receptor (sIL-6R) Concentration
sIL-6R concentration was determined, averaged among all participants, and expressed in nanograms per milliliter (ng/mL).
Measured: Predose (30 minutes) at baseline; Weeks 12, 24; and FU Week 8 (up to 32 weeks overall)
Change From Baseline in Patient Global Assessment of Disease Activity According to VAS
PGA of disease activity was scored 0-100 mm on a VAS, where higher scores indicate greater perceived disease activity. Change from baseline was averaged among all participants. Negative values indicate improvement/reduction in RA disease activity.
Measured: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
Change From Baseline in Patient Global Assessment of RA-Related Pain According to VAS
PGA of RA-related pain was scored 0-100 mm on a VAS, where higher scores indicate greater perceived pain. Change from baseline was averaged among all participants. Negative values indicate improvement/reduction in RA-related pain.
Measured: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
Change From Baseline in HAQ-DI Score
HAQ-DI consisted of 20 questions assessing ADLs in 8 domains (dress/groom, arise, eat, walk, reach, grip, hygiene) with each item rated 0 (no difficulty) to 3 (unable to do). The highest score recorded for any question in a domain determined the score for that domain, unless assistance was required. The total HAQ-DI score was the sum of domain scores divided by the number of domains answered/scored, for a single score range of 0-3, where higher scores indicate increased functional disability. Change from baseline was averaged among all participants. Negative values indicate improvement in ability to perform ADLs.
Measured: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
Compliance With Treatment According to Percentage of Injections Administered
Participants were provided with diary cards to record home injections. Compliance with treatment was calculated individually for each participant as the actual number of injections as a percentage of the planned number of injections (up to the point of discontinuation for those who discontinued study treatment prematurely) and then averaged among all participants.
Measured: Baseline up to Week 24
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score
FACIT-F consisted of 40 questions/statements assessing chronic illness therapy with special emphasis on fatigue over the past 7 days, with each item rated 0 (not at all) to 4 (very much). During score calculations, negatively-worded item scales (e.g., "I have a lack of energy") were reversed so that higher scores indicated more favorable conditions. The total FACIT-F score was the sum of all item scores and ranged 0-160, and the brief FACIT-F score was the sum of 13 item scores and ranged 0-52, where higher scores indicate greater well-being. Change from baseline was averaged among all participants. Positive values indicate improvement in well-being.
Measured: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2014 (estimated)
- Study start28 May 2014
- Primary completion13 Sep 2016
- Study completion13 Sep 2016
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 (4)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 133 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02046616
- Sponsor's protocol ID
- ML28691
- Other IDs
- 2013-002007-34
- Status last verified
- Apr 2018
- First submitted
- 24 Jan 2014
- Last updated
- 13 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Hammer HB, Jensen Hansen IM, Jarvinen P, Leirisalo-Repo M, Ziegelasch M, Agular B, Terslev L. Rheumatoid arthritis patients with predominantly tender joints rarely achieve clinical remission despite being in ultrasound remission. Rheumatol Adv Pract. 2021 May 14;5(2):rkab030. doi: 10.1093/rap/rkab030. eCollection 2021.
PubMed 34131623Hammer HB, Hansen I, Jarvinen P, Leirisalo-Repo M, Ziegelasch M, Agular B, Terslev L. Major reduction of ultrasound-detected synovitis during subcutaneous tocilizumab treatment: results from a multicentre 24 week study of patients with rheumatoid arthritis. Scand J Rheumatol. 2021 Jul;50(4):262-270. doi: 10.1080/03009742.2020.1845394. Epub 2021 Jan 19.
PubMed 33464147Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Devenport J, Petho-Schramm A. Effects of concomitant glucocorticoids in TOZURA, a common-framework study programme of subcutaneous tocilizumab in rheumatoid arthritis. Rheumatology (Oxford). 2019 Jun 1;58(6):1056-1064. doi: 10.1093/rheumatology/key393.
PubMed 30649524Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Bernasconi C, Petho-Schramm A. Subcutaneous tocilizumab in rheumatoid arthritis: findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries. Rheumatology (Oxford). 2018 Mar 1;57(3):499-507. doi: 10.1093/rheumatology/kex443.
PubMed 29244149
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tocilizumab SC in Patients With Active Rheumatoid Arthritis and Inadequate Response to DMARDs. A Single-Arm, Open-Label Study to Evaluate Safety, Tolerability and Efficacy. In a Subgroup of Patients Inflammation Will Be Measured by Ultrasound.
- ClinicalTrials.gov ID
- NCT02046616
- Acronym / sponsor ID
- ML28691
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 133 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 28 May 2014 (actual)
- Primary completion
- 13 Sep 2016 (actual)
- Study completion
- 13 Sep 2016 (actual)
- First posted
- 28 Jan 2014 (estimated)
- Results
- Posted 13 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase IIIb, open-label, single-arm study will evaluate the safety, efficacy, and tolerability of SC tocilizumab (RoActemra/Actemra) in monotherapy or in combination with methotrexate or other non-biologic DMARDs in participants with active RA who are naive to tocilizumab. Participants will receive tocilizumab 162 milligrams (mg) subcutaneously weekly (QW) for 24 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tocilizumab Alone or Combined with Methotrexate or Other DMARD | Experimental | Drug: Tocilizumab, Drug: Methotrexate, Drug: Non-Biologic DMARDsAll participants will receive tocilizumab as a single fixed dose (monotherapy) or in combination with methotrexate or other non-biologic DMARDs, irrespective of body weight, for 24 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Active RA according to the revised ACR (1987) criteria or EULAR/ACR (2010) criteria
- Moderate to severe RA with a DAS28-ESR score >3.2 points
- Inadequate response and/or intolerance to MTX or other non-biologic DMARDs and/or where MTX or other non-biologic DMARDs are inappropriate
- Oral corticosteroids (less than or equal to [</=] 10 mg per day prednisolone or equivalent) and nonsteroidal anti-inflammatory drugs (NSAIDs) permitted if on stable dose regimen for greater than or equal to [>/=] 4 weeks prior to baseline
- Permitted non-biologic DMARDs allowed if at stable dose for >/=4 weeks prior to baseline
Key exclusion criteria (18 listed)
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline
- Rheumatic autoimmune disease other than RA
- Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
- Diagnosis of juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16
- Prior history of or current inflammatory joint disease other than RA
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 |
|---|---|---|
| TocilizumabAlso: RoActemra, ActemraTocilizumab 162 mg will be administered subcutaneously QW. | Drug | Tocilizumab Alone or Combined with Methotrexate or Other DMARD |
| MethotrexateMethotrexate dosing is not specified by the protocol and will be given as per standard practice. Participants must be at a stable dose that was initiated at least 4 weeks prior to baseline. | Drug | Tocilizumab Alone or Combined with Methotrexate or Other DMARD |
| Non-Biologic DMARDsParticipants will receive non-biologic DMARDs (same non-biologic DMARD that participant was receiving at time of study entry). Dosing is not specified by the protocol and will be given as per standard practice. Participants must be at a stable dose that was initiated at least 4 weeks prior to baseline. | Drug | Tocilizumab Alone or Combined with Methotrexate or Other DMARD |
Primary outcome
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12
Time frame: Baseline, Week 12
CDAI was derived as the sum of the following: tender joint count (TJC), swollen joint count (SJC), participant global assessment (PGA) of disease activity, and physician assessment of disease activity. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA and physician assessment of disease activity were scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity. The total CDAI score range was 0-76, where higher scores indicate increased disease activity. Change from baseline was averaged among all participants. Negative values indicate improvement/reduction in RA disease activity.
16 secondary outcomes
Change From Baseline in Disease Activity Score 28 (DAS28)-Erythrocyte Sedimentation Rate (ESR) Score
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
Percentage of Participants With American College of Rheumatology (ACR) Response
Time frame: Weeks 2, 4, 8, 12, 16, 20, 24
Percentage of Participants With European League Against Rheumatism (EULAR) Response
Time frame: Weeks 2, 4, 8, 12, 16, 20, 24
Change From Baseline in CDAI at Weeks 2, 4, 8, 16, 20, and 24
Time frame: Baseline and Weeks 2, 4, 8, 16, 20, 24
Change From Baseline in Simplified Disease Activity Index (SDAI)
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
Change From Baseline in TJC
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
Change From Baseline in SJC
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
Percentage of Participants With At Least One Adverse Event Leading to Dosage Modification
Time frame: Baseline up to Week 24
Number of Participants With Neutralizing Anti-Tocilizumab Antibodies
Time frame: Baseline to FU Week 8 (up to 32 weeks overall)
Tocilizumab Concentration
Time frame: Predose (30 minutes) at baseline; Weeks 12, 24; and FU Week 8 (up to 32 weeks overall)
Soluble Interleukin-6 Receptor (sIL-6R) Concentration
Time frame: Predose (30 minutes) at baseline; Weeks 12, 24; and FU Week 8 (up to 32 weeks overall)
Change From Baseline in Patient Global Assessment of Disease Activity According to VAS
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
Change From Baseline in Patient Global Assessment of RA-Related Pain According to VAS
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
Change From Baseline in HAQ-DI Score
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
Compliance With Treatment According to Percentage of Injections Administered
Time frame: Baseline up to Week 24
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34131623Hammer HB, Jensen Hansen IM, Jarvinen P, Leirisalo-Repo M, Ziegelasch M, Agular B, Terslev L. Rheumatoid arthritis patients with predominantly tender joints rarely achieve clinical remission despite being in ultrasound remission. Rheumatol Adv Pract. 2021 May 14;5(2):rkab030. doi: 10.1093/rap/rkab030. eCollection 2021.
- Derived from this study: PubMed 33464147Hammer HB, Hansen I, Jarvinen P, Leirisalo-Repo M, Ziegelasch M, Agular B, Terslev L. Major reduction of ultrasound-detected synovitis during subcutaneous tocilizumab treatment: results from a multicentre 24 week study of patients with rheumatoid arthritis. Scand J Rheumatol. 2021 Jul;50(4):262-270. doi: 10.1080/03009742.2020.1845394. Epub 2021 Jan 19.
- Derived from this study: PubMed 30649524Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Devenport J, Petho-Schramm A. Effects of concomitant glucocorticoids in TOZURA, a common-framework study programme of subcutaneous tocilizumab in rheumatoid arthritis. Rheumatology (Oxford). 2019 Jun 1;58(6):1056-1064. doi: 10.1093/rheumatology/key393.
- Derived from this study: PubMed 29244149Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Bernasconi C, Petho-Schramm A. Subcutaneous tocilizumab in rheumatoid arthritis: findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries. Rheumatology (Oxford). 2018 Mar 1;57(3):499-507. doi: 10.1093/rheumatology/kex443.
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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.
Clinical Trials study director
Hoffmann-La Roche
27 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tocilizumab, Methotrexate and Non-Biologic DMARDs in people with Rheumatoid Arthritis, run by Hoffmann-La Roche at 27 sites in 4 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 7 inclusion and 18 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 13 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in Sweden, Denmark, Finland, Norway. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 13 Apr 2018). 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?
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12 (time frame: Baseline, Week 12). 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 NCT02046616, which also lists 4 linked publications.
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 13 Apr 2018.