A Trial of Prednisolone in Combination With SPI-62 or Placebo in Subjects With Polymyalgia Rheumatica (PMR)

Study Overview
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Brief Summary
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This will be a single-blind, placebo-controlled phase 2 trial to compare prednisolone effects with and without SPI-62 in subjects with PMR.

Detailed Description
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This will be a single-blind, placebo-controlled phase 2 trial to compare prednisolone effects with and without SPI-62 in subjects with PMR. Up to 4 cohorts of 12 subjects could be recruited (12 to 48 subjects). Each subject who provides consent and meets all inclusion and exclusion criteria will participate in 3 periods: a screening period up to 28 days (Day -28 to Day-1), a 4-week treatment period (Day 1 to Day 28) and a follow up Period (Day 29 to Day 56). During the 4-week treatment period for the first cohort, all subjects will receive prednisolone 10mg per day for 4-weeks plus SPI-62 for 2-weeks and matching placebo for 2-weeks. For cohorts 2 through 4, the dose of prednisolone co-administered with SPI-62 could be adjusted.

Official Title
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A Trial of Prednisolone in Combination With SPI-62 or Placebo in Subjects With Polymyalgia Rheumatica (PMR)

Conditions
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Polymyalgia Rheumatica

Intervention / Treatment
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* Drug: SPI-62
* Drug: SPI-62 matched placebo
* Drug: Prednisolone 10mg
* Drug: Additional prednisolone
* Drug: Additional prednisolone matched placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Diagnosis of PMR according to EULAR/ACR classification criteria Absence of PMR relapse based on symptoms and acute phase markers Daily oral prednisolone 10mg dose that will have been stable for at least 1-week at the Baseline visit and is expected to remain stable during the treatment period Exclusion Criteria: Any contraindication for prednisolone administration. A diagnosis or any clinical features of giant cell arteritis. Any autoimmune disease (e.g., late-onset rheumatoid arthritis) other than PMR. Use of medications for treatment of PMR within specified intervals prior to the Baseline Visit other than oral prednisolone. Use of other medications likely to interfere with trial assessments. History or diagnosis of endogenous hypercortisolism. Any current or prior medical condition, medical or surgical therapies, or clinical trial participation expected to interfere with the conduct of the trial or the evaluation of its results.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPI-62<br>Active drug / placebo by mouth each morning for up to 4 weeks + standard of care 10mg prednisolone. Each participant will receive both placebo and active drug but will be blinded to the sequence of active drug and placebo. | Drug: SPI-62<br>* 11β hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor<br>Drug: SPI-62 matched placebo<br>* Inactive tablets identical in appearance to SPI-62 tablets<br>Drug: Prednisolone 10mg<br>* Standard of care prednisolone<br>|
| Experimental: SPI-62 + additional prednisolone<br>Active drug / placebo by mouth each morning for up to 4 weeks + standard of care 10mg prednisolone + additional prednisolone or placebo. Each participant will receive both placebo and active drug but will be blinded to the sequence of active drug and placebo. | Drug: SPI-62<br>* 11β hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor<br>Drug: SPI-62 matched placebo<br>* Inactive tablets identical in appearance to SPI-62 tablets<br>Drug: Prednisolone 10mg<br>* Standard of care prednisolone<br>Drug: Additional prednisolone<br>* Over encapsulated prednisolone<br>Drug: Additional prednisolone matched placebo<br>* Inactive capsules identical in appearance to over encapsulated prednisolone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Erythrocyte sedimentation rate |  | Baseline to Day 28 | 
| C-reactive protein |  | Baseline to Day 28 | 
| Plasma fibrinogen |  | Baseline to Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PMR, polymyalgia rheumatica, Steroids, Prednisolone, glucocorticoid, glucocorticoids