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

Novartis

Status and phase: Terminated; Phase 2

Conditions: Polymyalgia Rheumatica; Inflammatory Diseases

Treatments: Drug: AIN457; Drug: Prednisone; Drug: ACZ885; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01364389

2010-019395-73 (EudraCT Number)

CPJMR0012201

Details and patient eligibility

About

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.

Enrollment: 16 patients

Sex: All

Ages: 50 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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16 participants in 3 patient groups

ACZ885

Experimental group

Description:

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.

Treatment:

Drug: AIN457

Drug: Placebo

AIN457

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: ACZ885

Prednisone

Other group

Description:

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.

Treatment:

Drug: Placebo

Drug: Prednisone