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

Polymyalgia Rheumatica Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01364389
• Other study ID #: CPJMR0012201
• Secondary ID: 2010-019395-73
• Status: Terminated
• Phase: Phase 2
• Start date: February 14, 2011
• Est. completion date: January 29, 2013

Study information

• Verified date: August 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: January 29, 2013
• Est. primary completion date: January 29, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Giant Cell Arteritis
• Inflammatory Diseases
• Polymyalgia Rheumatica

Intervention

Drug:
• AIN457
3 mg/kg
• ACZ885
3 mg/kg
• Prednisone
20 mg
• Placebo
Matching placebo to AIN457, ACZ885 and prednisone

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Berlin
Italy	Novartis Investigative Site	Reggio Emilia	RE
Italy	Novartis Investigative Site	Siena	SI
United Kingdom	Novartis Investigative Site	Basildon	Essex
United Kingdom	Novartis Investigative Site	Westcliff-on-Sea	Essex
United States	Novartis Investigative Site	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Germany,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, Day 15
Secondary	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.	Day 15
Secondary	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.	Day 15
Secondary	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	6 months
Secondary	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.	6 months
Secondary	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.	6 months
Secondary	Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Deaths		6 months
Secondary	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.	6 months
Secondary	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.	6 months
Secondary	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.	baseline and at month 6
Secondary	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.	6 months
Secondary	Pharmacokinetics of AIN457 and ACZ885 - Cmax		Day 15
Secondary	Pharmacokinetics of AIN457 and ACZ885 - Tmax		Day 15
Secondary	Pharmacokinetics of AIN457 and ACZ885 - AUCinf and AUClast		Day 15
Secondary	Pharmacokinetics of AIN457 and ACZ885 - CL		Day 15
Secondary	Pharmacokinetics of AIN457 and ACZ885 - Vz		Day 15
Secondary	Pharmacokinetics of AIN457 and ACZ885 - T1/2		Day 15