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

• Register: EUCTR
• Last refreshed on: 10 December 2019
• Main ID: EUCTR2010-019395-73-GB
• Date of registration: 17/06/2010
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public 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
• Scientific 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
• Date of first enrolment: 20/09/2010
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019395-73
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: yes; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Italy, United Kingdom

Contacts

• Name: Medical Information Services
• Affiliation: Novartis Pharmaceuticals UK Ltd

• Name: Medical Information Services
• Affiliation: Novartis Pharmaceuticals UK Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
- Patients must be aged =50 and =85 at time of consent
-Patients with newly diagnosed PMR as well as patients with a history of PMR or previous PMR episodes treated with corticosteroids. Corticosteroid treatment must not have been within 3 months of the screening visit.
- All female subjects must have negative pregnancy test results at screening (serum) and baseline (urine)
- Male subjects must be using two highly effective methods of contraception, comprising a barrier method condom or occlusive cap plus spermicide) plus ensure use by the female partner of a second method of contraception
- Patients must meet all of the following criteria (based on BSR guideline on PMR):
• Age = 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 (at least 60 mins)
• Duration of illness > 1 week (at the time of initial diagnosis)
- Patient must be able to understand and communicate with the investigator, to understand and comply with the requirements of the study and must give a written, signed and dated informed consent before any study assessment is performed
- All patients receiving current vaccinations, especially influenza and pneumococcal as clinically indicated can be included. Patients should not receive any live vaccines (this includes nasal-spray flu vaccine) within 12 weeks before study entry and within 12 weeks of the last dose of AIN457 or ACZ885 (canakinumab)
- Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 17 to 35 kg/m2
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (>5 mIU/mL)
- Men who are planning to initiate a pregnancy while enrolled in the study or for 4 months following completion of the study, or who are not willing to follow the restrictions in inclusion criterion 3. Male or female patients who plan to conceive during the time course of the study and 6 months post last infusion of AIN457/ACZ885 (canakinumab)
- Presence of rheumatoid arthritis or other inflammatory arthritic processes (features of GCA (Giant Cell Arthrtitis), spondyloarthropathies, Osteoarthritis, symptomatic shoulder capsulitis), connective tissue disease, drug-induced myopathies, chronic pain syndromes, as assessed by base line screening including TSH, CK, RF, CCP, ANA, serum protein electrophoresis, urinalysis, -Ongoing treatment with corticosteroids
- Previous exposure to methotrexate or other immune suppressive agent within 3 months prior to randomization.
- Previous exposure to AIN457 or ACZ885 (canakinumab) or other biologic targeting IL-17, IL-17 receptor, IL-1b or IL-1ß receptor, or use of any investigational drug and/or devices within 4 weeks prior to randomization or 5 half-lives of the investigational agent, whichever is longer and for any other limitation of pariticipation based on local regulations.
- Active systemic infections during the last two weeks (exception: common cold) prior to randomization or current use of antibiotics.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

polymyalgia rheumatica
MedDRA version: 14.0 Level: PT Classification code 10036099 Term: Polymyalgia rheumatica System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Product Code: AIN457
Pharmaceutical Form: Powder for solution for injection
Current Sponsor code: CAIN457A
Other descriptive name: rhumAb to Il-17A (IgG1-k-class)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Trade Name: Ilaris
Product Name: Ilaris
Product Code: ACZ885
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: CANAKINUMAB
CAS Number: 914613-48-2
Current Sponsor code: ACZ885
Other descriptive name: Recombinant human monoclonal antibody
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Trade Name: Prednison Hexal
Product Name: Prednison Hexal
Pharmaceutical Form: Tablet
INN or Proposed INN: PREDNISONE
CAS Number: 53-03-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: - To assess the time to partial clinical response, time to complete response and time to first flare in patients who respond to a single dose of AIN457 or ACZ885 (canakinumab)
- To assess the effect of AIN457 and ACZ885 (canakinumab) on the number of flares over a 6 month period
- To assess the effect of AIN457 and ACZ885 (canakinumab) on the cumulative and/or mean steroid dose over a 6 month period
- To assess the safety and tolerability of AIN457 and ACZ885 (canakinumab) in patients with polymyalgia rheumatica
- To characterize the PKs of AIN457 and ACZ885 (canakinumab) in patients with polymyalgia rheumatica
- To compare the initial response to AIN457 and ACZ885 (canakinumab) with the response after redosing of AIN457 and ACZ885 (canakinumab)
- To assess the effect on health-related quality of life (HAQ, SF-36)
- To assess the potential for immunogenicity induced by ACZ885 (canakinumab) / AIN457 in PMR patients

Primary end point(s): The primary endpoint of the study is the PMR-AS on Day 15

Main Objective: - To assess the efficacy of a single dose of AIN457 after 2 weeks as measured by the polymyalgia rheumatica activity score.
- To assess the efficacy of a single dose of ACZ885 (canakinumab) after 2 weeks as measured by the polymyalgia rheumatica activity score.

Secondary ID(s)

CPJMR0012201

Source(s) of Monetary Support

Novartis Pharma AG

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 15/04/2016
• Date Completed: 29/01/2013
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-019395-73/results