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
  Purpose

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.


Condition Intervention Phase
Polymyalgia Rheumatica
Inflammatory Diseases
Drug: AIN457
Drug: ACZ885
Drug: Prednisone
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 16
Study Start Date: February 2011
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: AIN457
3 mg/kg
Drug: Placebo
Matching placebo to AIN457, ACZ885 and prednisone
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.
Drug: ACZ885
3 mg/kg
Other Name: canakinumab
Drug: Placebo
Matching placebo to AIN457, ACZ885 and prednisone
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.
Drug: Prednisone
20 mg
Drug: Placebo
Matching placebo to AIN457, ACZ885 and prednisone

  Eligibility

Ages Eligible for Study:   50 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01364389

Locations
United States, Minnesota
Novartis Investigative Site
Rochester, Minnesota, United States, 55905
Germany
Novartis Investigative Site
Berlin, Germany, 13125
Italy
Novartis Investigative Site
Reggio Emilia, RE, Italy, 42123
Novartis Investigative Site
Siena, SI, Italy, 53100
United Kingdom
Novartis Investigative Site
Essex, United Kingdom, SS16 5NL
Novartis Investigative Site
Westcliff-on-Sea, United Kingdom, SS0 0RY
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01364389     History of Changes
Other Study ID Numbers: CPJMR0012201, 2010-019395-73
Study First Received: March 10, 2011
Results First Received: February 17, 2015
Last Updated: March 10, 2015
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Germany: Ministry of Health

Keywords provided by Novartis:
Polymyalgia Rheumatica
Inflammatory Disease
Rheumatic Disease

Additional relevant MeSH terms:
Dermatomyositis
Giant Cell Arteritis
Polymyalgia Rheumatica
Arteritis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Connective Tissue Diseases
Immune System Diseases
Muscular Diseases
Musculoskeletal Diseases
Myositis
Nervous System Diseases
Neuromuscular Diseases
Polymyositis
Rheumatic Diseases
Skin Diseases
Skin Diseases, Vascular
Vascular Diseases
Vasculitis
Vasculitis, Central Nervous System
Prednisone
Anti-Inflammatory Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on April 23, 2015