A clinical study, assessing the effect of 2 new drugs (AIN457, ACZ885) as compared to a standard drug (corticosteroids) to relief pain and inflammation in patients with Polymyalgia rheumatica (PMR)

• Register: EUCTR
• Last refreshed on: 18 February 2013
• Main ID: EUCTR2010-019395-73-DE
• Date of registration: 30/09/2010
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A clinical study, assessing the effect of 2 new drugs (AIN457, ACZ885) as compared to a standard drug (corticosteroids) to relief pain and inflammation in patients with Polymyalgia rheumatica (PMR)
• 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: 22/12/2010
• 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: yes Other trial design description: double dummy If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Germany, Italy, United Kingdom, United States

Contacts

• Name: Medizinischer Infoservice
• Affiliation: Novartis Pharma GmbH

• Name: Medizinischer Infoservice
• Affiliation: Novartis Pharma GmbH

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 7 days of thescreening 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 minutes)
• 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 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

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: 14.1 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 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 150 mg Pulver zur Herstellung einer Injektionslösung
Product Name: Ilaris
Product Code: ACZ885
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Canacinumab
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 20 mg
Product Name: Prednison Hexal 20 mg
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: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

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 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

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

Primary end point(s): the PMR-AS

Secondary Outcome(s)

Secondary end point(s): - 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: Described in section E.5.2

Secondary ID(s)

2010-019395-73-GB

CPJMR0012201

Source(s) of Monetary Support

Novartis Pharma Services AG