Clinical trial NCT01364389: A 3-arm Proof of Concept Study of AIN457, ACZ885 or Corticosteroids in Patients With Polymyalgia Rheumatica
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Polymyalgia Rheumatica
Inflammatory Diseases
Keywords: Polymyalgia Rheumatica
Inflammatory Disease
Rheumatic Disease
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-06-02
Enrollment: 16
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Polymyalgia Rheumatica Activity Score (PMR-AS)
timeFrame: Baseline, Day 15
Secondary outcomes:
measure: Time to Partial Clinical Response
timeFrame: Day 15
measure: Time to Complete Clinical Response
timeFrame: Day 15
measure: Time to First Flare
timeFrame: 6 months
measure: Number of Flares Over a 6 Month Period
timeFrame: 6 months
measure: Mean Steroid Dose Over a 6 Month Period
timeFrame: 6 months
measure: Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Deaths
timeFrame: 6 months
measure: 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.
timeFrame: 6 months
measure: Effect on Health-related Quality of Life Via the Short Form-36 (SF-36) Questionnaire
timeFrame: 6 months
measure: Effect on Health-related Quality of Life Via the Health Assessment Questionnaire (HAQ)
timeFrame: baseline and at month 6
measure: 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
timeFrame: 6 months
measure: Pharmacokinetics of AIN457 and ACZ885 - Cmax
timeFrame: Day 15
measure: Pharmacokinetics of AIN457 and ACZ885 - Tmax
timeFrame: Day 15
measure: Pharmacokinetics of AIN457 and ACZ885 - AUCinf and AUClast
timeFrame: Day 15
measure: Pharmacokinetics of AIN457 and ACZ885 - CL
timeFrame: Day 15
measure: Pharmacokinetics of AIN457 and ACZ885 - Vz
timeFrame: Day 15
measure: Pharmacokinetics of AIN457 and ACZ885 - T1/2
timeFrame: Day 15
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Reggio Emilia
country: Italy
facility: Novartis Investigative Site
state: RE
city: Siena
country: Italy
facility: Novartis Investigative Site
state: SI
city: Basildon
country: United Kingdom
facility: Novartis Investigative Site
state: Essex
city: Westcliff-on-Sea
country: United Kingdom
facility: Novartis Investigative Site
state: Essex
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: