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

This study has been terminated.
(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.)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01364389
First received: March 10, 2011
Last updated: March 10, 2015
Last verified: March 2015

March 10, 2011
March 10, 2015
February 2011
January 2013   (final data collection date for primary outcome measure)
Polymyalgia Rheumatica Activity Score (PMR-AS) [ Time Frame: Baseline, Day 15 ] [ Designated as safety issue: No ]
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.
To assess the efficacy of a single dose of AIN457 and ACZ885 (canakinmab) separately after 2 weeks as measured by the polymyalgia rheumatica activity score. [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01364389 on ClinicalTrials.gov Archive Site
  • Time to Partial Clinical Response [ Time Frame: Day 15 ] [ Designated as safety issue: No ]

    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 VAS compared with baseline and morning stiffness < 60 minutes.

  • Time to Complete Clinical Response [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
    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 to First Flare [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Number of Flares Over a 6 Month Period [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Cumulative and/or Mean Steroid Dose Over a 6 Month Period [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Deaths [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics of AIN457 and ACZ885 [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
  • Comparison Between the Initial Response to AIN457 and ACZ885 and the Response After Re-dosing of AIN457 and ACZ885 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Effect on Health-related Quality of Life [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To assess the time to partial clinical response in patients who respond to a single dose of AIN457 or ACZ885 (canakinumab) with daily monitoring (homebased) of the lab parameter CRP, an indicator of inflammation [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To assess the time to complete response (days) in responders to a single dose of either AIN457 or ACZ885 (canakinumab) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To assess the time to first flare in patients who respond to a single dose of AIN457 or ACZ885 (canakinumab) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To assess the effect of AIN457 and ACZ885 (canakinumab) on the number of flares over a 6 month period [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To assess the effect of AIN457 and ACZ885 (canakinumab) on the cumulative and/or mean steroid dose over a 6 month period [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To assess the safety and tolerability of AIN457 and ACZ885 (canakinumab) in patients with polymyalgia rheumatica by monitoring different standard lab parameters throughout the study period and collecting information on adverse events including infections [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • To characterize the concentrations (Pharmacokinetics) of AIN457 and ACZ885 (canakinumab) in blood serum in patients with polymyalgia rheumatica [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • To compare the initial response to AIN457 and ACZ885 (canakinumab) with the response after re-dosing of AIN457 and ACZ885 (canakinumab) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To assess the effect on health-related quality of life (HAQ, SF-36) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A 3-arm Proof of Concept Study of AIN457, ACZ885 or Corticosteroids in Patients With Polymyalgia Rheumatica
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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
  • Polymyalgia Rheumatica
  • Inflammatory Diseases
  • Drug: AIN457
    3 mg/kg
  • Drug: ACZ885
    3 mg/kg
    Other Name: canakinumab
  • Drug: Prednisone
    20 mg
  • Drug: Placebo
    Matching placebo to AIN457, ACZ885 and prednisone
  • Experimental: ACZ885
    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.
    Interventions:
    • Drug: AIN457
    • Drug: Placebo
  • Experimental: AIN457
    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.
    Interventions:
    • Drug: ACZ885
    • Drug: Placebo
  • Prednisone
    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.
    Interventions:
    • Drug: Prednisone
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
16
January 2013
January 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must meet all of the following features:
  • Patients ≥ 50 and ≤ 85 years
  • CRP > 1.0 mg/dl OR 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 PPD skin test (≤ 5 mm induration) at screening

Exclusion Criteria:

  • Active infection or current use of antibiotics
  • Known HIV, HCV or 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 GCA (Giant Cell Artertitis), spondyloarthropathies), connective tissue disease, drug-induced myopathies, endocrine disorders, neurological disorders, chronic pain syndromes, as assessed by base line screening including TSH, CK, RF, CCP, ANA, serum protein electrophoresis, urinalysis.

Other protocol-defined inclusion/exclusion criteria apply

Both
50 Years to 85 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Germany,   Italy,   United Kingdom
Australia
 
NCT01364389
CPJMR0012201, 2010-019395-73
Not Provided
Not Provided
Not Provided
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP