A 2-week study in patients with polymyalgia rheumatica

• Register: EUCTR
• Last refreshed on: 25 March 2013
• Main ID: EUCTR2010-019395-73-IT
• Date of registration: 28/02/2012
• Prospective Registration: No
• Primary sponsor: NOVARTIS FARMA
• Public title: A 2-week study in patients with polymyalgia rheumatica
• 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: 25/07/2011
• Target sample size: 35
• 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 Number of treatment arms in the trial: 3

Countries of recruitment

Germany, Italy, United Kingdom, United States

Contacts

• Name: Drug Regulatory Affairs
• Affiliation: Novartis Farma

• Name: Drug Regulatory Affairs
• Affiliation: Novartis Farma

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients must be aged `?¥50 and `?¤85 at time of consent. 2. 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. 3. All female subjects must have negative pregnancy test results at screening (serum) and baseline (urine). Women of childbearing potential (WoCBP) must be using simultaneously doublebarrier or two acceptable methods of contraception, (e.g. intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc., hormonal contraception as either oral or implantable is acceptable as one form), from the time of screening and for the duration of the study, through study completion and for 4 months following study completion and for 6 months post last dose of AIN457 / ACZ885 (canakinumab). Women on hormone contraception should be on this regimen for at least 2 months prior to study start. Postmenopausal females must have had no regular bleeding for at least two (2) years prior to initial dosing. If menopause is confirmed by a plasma FSH level of <40 IU/L at screening, pregnancy test will only be required at screening or consistent with menopause per local laboratory, pregnancy tests will be required before each infusion. Female subjects who report surgical sterilization must have had the procedure at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and/or Principle Investigator and noted in the Relevant Medical History / Current Medical Conditions section in the eCRF. If female subjects have male partners who have undergone vasectomy, the vasectomy must have occurred more than six (6) months prior to first dosing. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. 4. 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. These measures should be in place for the entire duration of the study up the Study Completion visit, and males should refrain from fathering a child in at least 6 months post last dose of AIN457/ACZ885 (canakinumab) 5. 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 minutes) • Duration of illness > 1 week (at the time of initial diagnosis) 6. 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. 7. 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). 8. 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. See Appendix 3 of this protocol for BMI ranges.
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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; - History of PMR and Previous PMR episodes treated with steroids; - 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-1β 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: 14.1 Level: PT Classification code 10036099 Term: Polymyalgia rheumatica System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Name: NA
Product Code: AIN457
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Secukinumab
Current Sponsor code: AIN457A
Other descriptive name: rhumAb to Il-17A (IgG1-k-class)
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use

Trade Name: ILARIS*SC 1FL 150MG
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-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use

Trade 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)

Primary end point(s): 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.

Timepoint(s) of evaluation of this end point: Day 15

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 on the number of flares over a 6 month period; - To assess the effect of AIN457 and ACZ885 on the cumulative and/or mean steroid dose over a 6 month period; - To assess the safety and tolerability of AIN457 and ACZ885 in patients with polymyalgia rheumatic; - To characterize the PKs of AIN457 and ACZ885 in patients with polymyalgia rheumatic; - To compare the initial response to AIN457 and ACZ885 with the response after redosing of AIN457 and ACZ885; - To assess the effect on health-related quality of life (HAQ, SF-36); - To assess the potential for immunogenicity induced by ACZ885 / AIN457 in PMR patients.

Secondary Outcome(s)

Secondary end point(s): Secondary End Point - 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) using the PMR activity score. - To assess the effect of AIN457 and ACZ885 (canakinumab) on the number of flares over a 6 month period using the PMR activity score at 6 month timepoint. - To assess the effect of AIN457 and ACZ885 (canakinumab) on the cumulative and/or mean steroid dose over a 6 month period comparing the steroid use due to flares in patients after 6 months. - 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 from these patients. - To characterize the PKs of AIN457 and ACZ885 (canakinumab) in patients with polymyalgia rheumatica measured in blood serum samples. - To compare the initial response to AIN457 and ACZ885 (canakinumab) with the response after re-dosing of AIN457 and ACZ885 (canakinumab) using the PMR activity scores measured at these timepoints. - To assess the effect on health-related quality of life (HAQ, SF-36) by completion of respective patient reported outcome questionnaires. - To assess the potential for immunogenicity induced by ACZ885 (canakinumab) / AIN457 in PMR patients measured in blood serum samples.

Timepoint(s) of evaluation of this end point: As described in the Secondary end point.

Secondary ID(s)

2010-019395-73-GB

CPJMR0012201

Source(s) of Monetary Support

Novartis Pharma