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

Phase 2TerminatedNCT01364389

Novartis Pharmaceuticals16 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Polymyalgia Rheumatica Inflammatory Diseases

Interventions

Eligibility

Sex: ALLMin age: 50 YearsMax age: 85 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: Baseline, Day 15

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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.

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.

One participant experienced one flare after initial dose but this participant had no flare after a redose. This patient was in the AIN457 arm.

Time frame: 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.

Time frame: 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.

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

HAQ: The scores range from 0 (min) to 3 (max). Higher scores = more disability; lower scores = less disability.

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

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

Overview

Conditions

Interventions

Eligibility

Locations (6)

Outcomes

Primary Outcomes

Secondary Outcomes