Polymyalgia RheumaticaPhase 2NCT01364389
A 3-arm Proof of Concept Study of AIN457, ACZ885 or Corticosteroids in Patients With Polymyalgia Rheumatica
A Phase 2 study testing AIN457, ACZ885 and Prednisone in people with Polymyalgia Rheumatica and Inflammatory Diseases, run by Novartis Pharmaceuticals at 6 sites in 4 countries.
Trial summary
The study is a two-week, single-blinded, double-dummy, randomized, active-controlled, parallel group design, with a follow-up period up to a total study duration of 6-month, non-randomized, open-label phase to monitor safety, tolerability and, in responders, flare. It is a multicentric, multinational study. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Polymyalgia Rheumatica, Inflammatory Diseases
- What is being tested?
- AIN457, ACZ885 and Prednisone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 6 sitesin 4 countries
- Study dates
- 14 Feb 2011to 29 Jan 2013
- 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 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must meet all of the following features:
- Patients ≥ 50 and ≤ 85 years
- C-reactive protein (CRP) > 1.0 mg/dl OR erythrocyte sedimentation rate (ESR) > 30 mm/hr
- New bilateral shoulder and/or hip pain
- Early morning stiffness ≥ 60 min
- Duration of illness > 1 week
- A negative 5 U purified protein derivative skin test (PPD) skin test (≤ 5 mm induration) at screening
Who cannot join
- Active infection or current use of antibiotics
- Known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatits B virus (HBV)
- Previous therapy with methotrexate or other immunosuppressive agents within three months prior to baseline
- History of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix within five years prior to study entry
- Presence of rheumatoid arthritis or other inflammatory arthritic processes (features of Giant Cell Artertitis (GCA), spondyloarthropathies), connective tissue disease, drug-induced myopathies, endocrine disorders, neurological disorders, chronic pain syndromes, as assessed by base line screening including thyroid-stimulating hormone (TSH), creatine kinase (CK), rheumatoid factor (RF), cyclic citrullinated peptide (CCP), antinuclear antibodies (ANA), serum protein electrophoresis, urinalysis.
- Other protocol-defined inclusion/exclusion criteria apply
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
Italy2 sites
Novartis Investigative Site
Reggio Emilia, RE, 42123
Novartis Investigative Site
Siena, SI, 53100
United Kingdom2 sites
Novartis Investigative Site
Basildon, Essex, SS16 5NL
Novartis Investigative Site
Westcliff-on-Sea, Essex, SS0 0RY
United States1 site
Novartis Investigative Site
Rochester, Minnesota, 55905
About this study
Official title: A 2-week Single-blind, Randomized, 3-arm Proof of Concept Study of the Effects of AIN457 (Anti-IL17 Antibody), ACZ885 (Canakinumab, Anti-IL1b Antibody), or Corticosteroids in Patients With Polymyalgia Rheumatica, Followed by an Open Label Phase to Assess Safety and Long Term Efficacy
The study is a two-week, single-blinded, double-dummy, randomized, active-controlled, parallel group design, with a follow-up period up to a total study duration of 6-month, non-randomized, open-label phase to monitor safety, tolerability and, in responders, flare. It is a multicentric, multinational study. The protocol will seek to enroll a total of 30 patients, who will be randomized to the 3 arms at a ratio of 1:1:1.
Patients will have a maximum screening period of 7 days with randomization at D1 for a dosing period of 15 days followed by a follow up-period of 154 days, or 4 months (112 days) after their last biologic dose, whichever is greater, and followed by unblinded re-dosing in the case of a disease flare.
- Conditions
- Polymyalgia Rheumatica, Inflammatory Diseases
- Being tested
- AIN457, ACZ885, Prednisone, Placebo
- Keywords
- Polymyalgia Rheumatica, Inflammatory Disease, Rheumatic Disease
- Medical subject headings
- Polymyalgia Rheumatica, Rheumatic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AIN457Drug
3 mg/kg
ACZ885Drug
Also called canakinumab
3 mg/kg
PrednisoneDrug
20 mg
PlaceboDrug
Matching placebo to AIN457, ACZ885 and prednisone
| Study group | Role | What they receive |
|---|---|---|
| ACZ885 | Experimental | On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering. Receives: Drug: AIN457; Drug: Placebo |
| AIN457 | Experimental | On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering. Receives: Drug: ACZ885; Drug: Placebo |
| Prednisone | Other | On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study. Receives: Drug: Prednisone; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Polymyalgia Rheumatica Activity Score (PMR-AS)
The efficacy of a single dose of AIN457 and ACZ885 (canakinumab) was measured by the polymyalgia rheumatica activity score. A composite PMR-AS was developed from the following components: measure of C-reactive protein (CRP), measure of Erythrocyte Sedimentation Rate (ESR), assessment of early morning stiffness, assessment of the patient's elevation on upper limbs, patient's assessment of pain, and physician's global assessment of disease activity. Treatment effect was measured by the percent reduction in PMR-AS. N=3 for the ACZ885 arm because CRP values at Day 15 were missing for 2 participants.
Measured: Baseline, Day 15
Secondary outcomes (16)
Time to Partial Clinical Response
The time to partial clinical response was assessed in patients who received a single dose of AIN457 or ACZ885 (canakinumab). Daily monitoring (home-based) of CRP was performed. This outcome shows the percentage of patients who achieved a partial clinical response at Day 15. A participant was defined as a partial responder if the participant had:
>50% reduction in patient global assessment visual analogue scale (VAS) compared with baseline and morning stiffness < 60 minutes.
Measured: Day 15
Time to Complete Clinical Response
The time to complete clinical response was assessed in patients who received a single dose of AIN457 or ACZ885 (canakinumab). Daily monitoring (home-based) of CRP was performed. This outcome shows the percentage of patients who achieved a complete clinical response at Day 15. A participant was defined as a complete responder if the participant had: >70% reduction in patient global assessment VAS compared with baseline, morning stiffness < 30 min, CRP < 1.0 mg/dL and/or ESR < 30 mm/1st hr.
Measured: Day 15
Time to First Flare
This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. Only 1 participant experienced a flare, in the AIN457 treatment group. The flare for this one participant occurred on study day 44
Measured: 6 months
Number of Flares Over a 6 Month Period
This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurements for the outcome measure.
Measured: 6 months
Mean Steroid Dose Over a 6 Month Period
This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period. The summary statistics include patients with a valid measurements for the outcome measure.
Measured: 6 months
Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Deaths
Measured: 6 months
Comparison Between the Initial Response to AIN457 and ACZ885 and the Response After Re-dosing of AIN457 and ACZ885 - Assessed by the Number of Flares After Redosing.
One participant experienced one flare after initial dose but this participant had no flare after a redose. This patient was in the AIN457 arm.
Measured: 6 months
Effect on Health-related Quality of Life Via the Short Form-36 (SF-36) Questionnaire
The Short Form-36 (SF-36) Questionnaire is a 36-item questionnaire yields an 8-scale health profile as well as summary measures of individual patients.. The scores range for each subscale from 0 to 10, and the composite score ranges from 0 to 100, with higher scores indicative of better health.
Measured: 6 months
Effect on Health-related Quality of Life Via the Health Assessment Questionnaire (HAQ)
HAQ: The scores range from 0 (min) to 3 (max). Higher scores = more disability; lower scores = less disability.
Measured: baseline and at month 6
Effect on Health-related Quality of Life Via the Health Assessment Questionnaire (HAQ) - % Change From Baseline in the Standard Disability Score at EOS / Month 6
HAQ: The scores range from 0 (min) to 3 (max). Higher scores = more disability; lower scores = less disability.
Measured: 6 months
Pharmacokinetics of AIN457 and ACZ885 - Cmax
Measured: Day 15
Pharmacokinetics of AIN457 and ACZ885 - Tmax
Measured: Day 15
Pharmacokinetics of AIN457 and ACZ885 - AUCinf and AUClast
Measured: Day 15
Pharmacokinetics of AIN457 and ACZ885 - CL
Measured: Day 15
Pharmacokinetics of AIN457 and ACZ885 - Vz
Measured: Day 15
Pharmacokinetics of AIN457 and ACZ885 - T1/2
Measured: Day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2011 (estimated)
- Study start14 Feb 2011
- Primary completion29 Jan 2013
- Study completion29 Jan 2013
Why it stopped: Data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period.
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 Polymyalgia RheumaticaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01364389
- Sponsor's protocol ID
- CPJMR0012201
- Other IDs
- 2010-019395-73
- Status last verified
- Aug 2021
- First submitted
- 10 Mar 2011
- Last updated
- 17 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Sun MM, Pope JE. Polymyalgia rheumatica and giant cell arteritis: diagnosis and management. Curr Opin Rheumatol. 2025 Jan 1;37(1):32-38. doi: 10.1097/BOR.0000000000001059. Epub 2024 Oct 14.
PubMed 39400109
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 2-week Single-blind, Randomized, 3-arm Proof of Concept Study of the Effects of AIN457 (Anti-IL17 Antibody), ACZ885 (Canakinumab, Anti-IL1b Antibody), or Corticosteroids in Patients With Polymyalgia Rheumatica, Followed by an Open Label Phase to Assess Safety and Long Term Efficacy
- ClinicalTrials.gov ID
- NCT01364389
- Acronym / sponsor ID
- CPJMR0012201
- Conditions
- Polymyalgia Rheumatica, Inflammatory Diseases
- Keywords
- Polymyalgia Rheumatica, Inflammatory Disease, Rheumatic Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period.
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 14 Feb 2011 (actual)
- Primary completion
- 29 Jan 2013 (actual)
- Study completion
- 29 Jan 2013 (actual)
- First posted
- 2 Jun 2011 (estimated)
- Results
- Posted 4 Mar 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is a two-week, single-blinded, double-dummy, randomized, active-controlled, parallel group design, with a follow-up period up to a total study duration of 6-month, non-randomized, open-label phase to monitor safety, tolerability and, in responders, flare. It is a multicentric, multinational study. The protocol will seek to enroll a total of 30 patients, who will be randomized to the 3 arms at a ratio of 1:1:1.
Patients will have a maximum screening period of 7 days with randomization at D1 for a dosing period of 15 days followed by a follow up-period of 154 days, or 4 months (112 days) after their last biologic dose, whichever is greater, and followed by unblinded re-dosing in the case of a disease flare.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ACZ885 | Experimental | Drug: AIN457, Drug: PlaceboOn day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering. |
| AIN457 | Experimental | Drug: ACZ885, Drug: PlaceboOn day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering. |
| Prednisone | Other | Drug: Prednisone, Drug: PlaceboOn day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study. |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients must meet all of the following features:
- Patients ≥ 50 and ≤ 85 years
- C-reactive protein (CRP) > 1.0 mg/dl OR erythrocyte sedimentation rate (ESR) > 30 mm/hr
- New bilateral shoulder and/or hip pain
- Early morning stiffness ≥ 60 min
Key exclusion criteria (6 listed)
- Active infection or current use of antibiotics
- Known human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatits B virus (HBV)
- Previous therapy with methotrexate or other immunosuppressive agents within three months prior to baseline
- History of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix within five years prior to study entry
- Presence of rheumatoid arthritis or other inflammatory arthritic processes (features of Giant Cell Artertitis (GCA), spondyloarthropathies), connective tissue disease, drug-induced myopathies, endocrine disorders, neurological disorders, chronic pain syndromes, as assessed by base line screening including thyroid-stimulating hormone (TSH), creatine kinase (CK), rheumatoid factor (RF), cyclic citrullinated peptide (CCP), antinuclear antibodies (ANA), serum protein electrophoresis, urinalysis.
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 |
|---|---|---|
| AIN4573 mg/kg | Drug | ACZ885 |
| ACZ885Also: canakinumab3 mg/kg | Drug | AIN457 |
| Prednisone20 mg | Drug | Prednisone |
| PlaceboMatching placebo to AIN457, ACZ885 and prednisone | Drug | ACZ885, AIN457, Prednisone |
Primary outcome
Polymyalgia Rheumatica Activity Score (PMR-AS)
Time frame: Baseline, Day 15
The efficacy of a single dose of AIN457 and ACZ885 (canakinumab) was measured by the polymyalgia rheumatica activity score. A composite PMR-AS was developed from the following components: measure of C-reactive protein (CRP), measure of Erythrocyte Sedimentation Rate (ESR), assessment of early morning stiffness, assessment of the patient's elevation on upper limbs, patient's assessment of pain, and physician's global assessment of disease activity. Treatment effect was measured by the percent reduction in PMR-AS. N=3 for the ACZ885 arm because CRP values at Day 15 were missing for 2 participants.
16 secondary outcomes
Time to Partial Clinical Response
Time frame: Day 15
Time to Complete Clinical Response
Time frame: Day 15
Time to First Flare
Time frame: 6 months
Number of Flares Over a 6 Month Period
Time frame: 6 months
Mean Steroid Dose Over a 6 Month Period
Time frame: 6 months
Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Deaths
Time frame: 6 months
Comparison Between the Initial Response to AIN457 and ACZ885 and the Response After Re-dosing of AIN457 and ACZ885 - Assessed by the Number of Flares After Redosing.
Time frame: 6 months
Effect on Health-related Quality of Life Via the Short Form-36 (SF-36) Questionnaire
Time frame: 6 months
Effect on Health-related Quality of Life Via the Health Assessment Questionnaire (HAQ)
Time frame: baseline and at month 6
Effect on Health-related Quality of Life Via the Health Assessment Questionnaire (HAQ) - % Change From Baseline in the Standard Disability Score at EOS / Month 6
Time frame: 6 months
Pharmacokinetics of AIN457 and ACZ885 - Cmax
Time frame: Day 15
Pharmacokinetics of AIN457 and ACZ885 - Tmax
Time frame: Day 15
Pharmacokinetics of AIN457 and ACZ885 - AUCinf and AUClast
Time frame: Day 15
Pharmacokinetics of AIN457 and ACZ885 - CL
Time frame: Day 15
Pharmacokinetics of AIN457 and ACZ885 - Vz
Time frame: Day 15
Pharmacokinetics of AIN457 and ACZ885 - T1/2
Time frame: Day 15
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39400109Sun MM, Pope JE. Polymyalgia rheumatica and giant cell arteritis: diagnosis and management. Curr Opin Rheumatol. 2025 Jan 1;37(1):32-38. doi: 10.1097/BOR.0000000000001059. Epub 2024 Oct 14.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AIN457, ACZ885 and Prednisone in people with Polymyalgia Rheumatica and Inflammatory Diseases, run by Novartis Pharmaceuticals at 6 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 6 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: stopped early, as of the sponsor's last update on 17 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Italy, United Kingdom, United States, Germany. 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 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 4 Mar 2015). 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?
Polymyalgia Rheumatica Activity Score (PMR-AS) (time frame: Baseline, Day 15). 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 NCT01364389, 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 17 Sep 2021.