A 3-arm Proof of Concept Study of AIN457, ACZ885 or Corticosteroids in Patients With Polymyalgia Rheumatica

NCT01364389 | Terminated Phase 2 Results

• 2 other identifiers: CPJMR00122012010-019395-73
• Study Type: interventional
• Target: 16
• Locations: 4 countries
• Sites: 6

Brief 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. 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

Keywords

Polymyalgia Rheumatica; Inflammatory Disease; Rheumatic Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, Day 15

Secondary Outcomes (16)

• Time to Partial Clinical Response

  Day 15

• Time to Complete Clinical Response

  Day 15

• Time to First Flare

  6 months

• Number of Flares Over a 6 Month Period

  6 months

• Mean Steroid Dose Over a 6 Month Period

  6 months

Study Arms (3)

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.

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.

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.

Drug: Prednisone; Drug: Placebo

Interventions

AIN457 DRUG

3 mg/kg

ACZ885

ACZ885 DRUG

3 mg/kg

Also known as: canakinumab

AIN457

Prednisone DRUG

20 mg

Prednisone

Placebo DRUG

Matching placebo to AIN457, ACZ885 and prednisone

ACZ885; AIN457; Prednisone

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (6)

Novartis Investigative Site

Rochester, Minnesota, 55905, United States

Location

Novartis Investigative Site

Berlin, 13125, Germany

Location

Novartis Investigative Site

Reggio Emilia, RE, 42123, Italy

Location

Novartis Investigative Site

Siena, SI, 53100, Italy

Location

Novartis Investigative Site

Basildon, Essex, SS16 5NL, United Kingdom

Location

Novartis Investigative Site

Westcliff-on-Sea, Essex, SS0 0RY, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 39400109 DERIVED

MeSH Terms

Conditions

Polymyalgia Rheumatica; Rheumatic Diseases

Interventions

secukinumab; canakinumab; Prednisone

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

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.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2011
• First Posted: June 2, 2011
• Study Start: February 14, 2011
• Primary Completion: January 29, 2013
• Study Completion: January 29, 2013
• Last Updated: September 17, 2021
• Results First Posted: March 4, 2015

Record last verified: 2021-08

Locations

GB (2); DE (1); US (1); IT (2)