| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10036099 |
| E.1.2 | Term | Polymyalgia rheumatica |
| E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
- 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. |
|
| E.2.2 | Secondary objectives of the trial |
- 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 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 |
|
| E.4 | Principal 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-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 |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | 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. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Described in section E.5.2 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
|
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | Yes |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 5 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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