Primary:-To evaluate the efficacy of KEVZARA (sarilumab) in patients with polymyalgia rheumatica (PMR) as assessed by the proportion of subjects with sustained remission for sarilumab with a shorter corticosteroid (CS) tapering regimen as compared…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Proportion of patients achieving sustained remission at Week 52
Secondary outcome
Summary of the components of sustained remission composite measure at week 52
Total cumulative corticosteroid (including prednisone) dose over 52 weeks
Time to first polymyalgia rheumatica (PMR) flare
Changes from baseline in the glucocoritcoid toxicity index and its components
up to week 52
Number of adverse events up to week 58
Pharmacokinetic: Serum concentrations of sarilumab up to week 58
Background summary
It is still not known what causes PMR but research suggests that the symptoms
of PMR are related to the inflammation not only in the shoulder and hip joints
themselves but also due to inflammation of the bursae(or sacs) and tendons
surrounding these joints.
The current standard of care for GCA is corticosteroid therapy. Although high
dose CSs have generally been effective for the treatment of acute disease and
control of inflammation, usually a year or more of coritcosteroid (CS) therapy
is required for maintenance of
remission or control of disease activity. However, long term use of
corticosteroids can cause severe side effects.
Interleukin-6 (IL-6) is a protein of the immune system which proves to play a
significant rol in GCA. Recent studies demonstrate that blocking the IL-6
protein could be an adequate treatment for GCA.
Sarilumab, the study treatment, belongs to the group of monoclonal antibodies.
It blocks the receptor of the IL-6 protein. It is registered wordwide for the
treatment of rheumatoid arteritis.
Study objective
Primary:
-To evaluate the efficacy of KEVZARA (sarilumab) in patients with polymyalgia
rheumatica (PMR) as assessed by the proportion of subjects with sustained
remission for sarilumab with a shorter corticosteroid (CS) tapering regimen as
compared to placebo with a longer CS tapering regimen.
Secondary:
-To demonstrate the efficacy of sarilumab in patients with polymyalgia
rheumatica compared to placebo, in combination with a CS taper with regards to:
*Clinical responses (such as components of sustained remission, disease
remission rates, time to first disease flare) over time.
*Cumulative CS (including prednisone) exposure.
-To assess the safety (including immunogenicity) and tolerability of sarilumab
in patients with PMR.
-To measure sarilumab serum concentrations in patients with PMR.
-To assess the effect of sarilumab in reducing glucocorticoid toxicity as
measured by the composite glucocorticoid toxicity index questionnaire.
Study design
A phase 3, randomized, double blind, 2 arm parallel.
Intervention
Group 1: Sarilumab injection once every 2 weeks plus prednisone taper regimen
of 14 weeks
Group 2: Placebo injection matching sarilumab once every 2 weeks plus
prednisone taper regimen of 52 weeks
Study burden and risks
Risks and burdens related to blood collection, study procedures and possible
adverse events.
Kampenringweg 45E -
Gouda 2803 PE
NL
Kampenringweg 45E -
Gouda 2803 PE
NL
Listed location countries
Age
Inclusion criteria
-Diagnosis of polymyaglia rheumatica (PMR) according to European League Against Rheumatism/American College of Rheumatology classification criteria.
-Patients must be on prednisone of at least 7.5 mg/day (or equivalent) and not exceeding 20 mg/day at screening and during the screening period.
-Patient is willing and able to take prednisone of 15 mg/day at randomization.
-Patients must have a history of being treated for at least 8 weeks with prednisone (>=10 mg/day or equivalent).
-Patient must have had at least one episode of unequivocal PMR flare while attempting to taper prednisone at a dose that is >=7.5 mg/day (or equivalent) within the past 12 Weeks prior to screening:
-Unequivocal symptoms of PMR flare include shoulder and/or hip girdle pain associated with inflammatory stiffness.
-Patients must have erythrocyte sedimentation rate >=30 mm/hr and/or C-reactive protein >=10 mg/L associated with PMR disease activity within 12 weeks prior to screening.
Exclusion criteria
-Diagnosis of giant cell arteritis.
-Diagnosis of active fibromyalgia.
-Concurrent rheumatoid arthritis or other inflammatory arthritis or other connective tissue diseases. -Concurrent diagnosis of rhabdomyolysis or neuropathic muscular diseases.
-Inadequately treated hypothyroidism.
-Organ transplant recipient.
-Therapeutic failure including inadequate response or intolerance, or contraindication, to biological IL-6 antagonist.
-Any prior (within the defined period below) or concurrent use of immunosuppressive therapies (as specified in protocol).
-Unstable methotrexate (MTX) dose and/or MTX dose >15mg/week within 3 months of baseline.
-Concurrent use of systemic CS for conditions other than PMR.
-Pregnant or breastfeeding woman.
-Patients with active or untreated latent tuberculosis.
-Patients with history of invasive opportunistic infections.
-Patients with fever associated with infection or chronic, persistent or recurring infections requiring active treatment.
-Patients with uncontrolled diabetes mellitus.
-Patients with non-healed or healing skin ulcers.
-Patients who received any live, attenuated vaccine within 3 months of baseline.
-Patients who are positive for hepatitis B, hepatitis C and/or HIV.
-Patients with a history of active or recurrent herpes zoster.
-Patients with a history of or prior articular or prosthetic joint infection.
-Prior or current history of malignancy.
-Patients who have had surgery within 4 weeks of screening or planned surgery during study.
-Patients with a history of inflammatory bowel disease or severe diverticulitis or previous gastrointestinal perforation.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-002989-42-NL |
| ClinicalTrials.gov | NCT03600818 |
| CCMO | NL66756.058.18 |