A Double-Blind Study Evaluating Duvelisib in Subjects With Moderate to Severe Rheumatoid Arthritis and an Inadequate Response to Methotrexate Alone

Study Overview
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Brief Summary
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The purpose of this study is to investigate the safety and efficacy of multiple dose levels of the investigational product (study drug), IPI-145, in combination with methotrexate compared to methotrexate alone in subjects with active moderate-to-severe Rheumatoid Arthritis.

Detailed Description
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This Phase 2 study is designed to examine the efficacy and safety of multiple dose levels of IPI-145 in subjects with active moderate-to-severe Rheumatoid Arthritis receiving a background stable dose of methotrexate. The study will employ a randomized, double-blind, placebo-controlled, parallel design. Approximately 316 adult subjects who meet all eligibility criteria at Screening will be randomized at Baseline in a 1:1:1:1 ratio to one of 4 dose groups. All treatments will be administered twice a day (BID). After randomization, subjects will enter a 12-week Treatment Period, where study drug (IPI-145 or placebo) will be self-administered BID as an outpatient. During the Treatment Period, subjects will return to the clinic for efficacy and safety assessments every 2 weeks. Following Treatment Period completion at Week 12, subjects will enter a 3-week Follow-up Period which includes one clinic visit approximately 3 weeks after the last dose of study drug.

Official Title
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A Phase 2, Double-Blind, Parallel, Placebo-Controlled, Randomized Study to Evaluate Multiple Dose Levels of Duvelisib With Background Methotrexate in Subjects With Active Rheumatoid Arthritis and an Inadequate Response to Methotrexate Alone

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: IPI-145
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of Rheumatoid Arthritis for at least 6 months Active disease, based on Screening clinical and laboratory criteria, despite taking methotrexate for at least 3 months Exclusion Criteria: Pregnant or lactating females Previous failure or inadequate response to >2 biologic disease-modifying anti-rheumatic drugs (DMARDs) Concurrent DMARD treatment other than methotrexate, sulfasalazine, chloroquine, or hydroxychloroquine Treatment with > 10 mg daily prednisone (or equivalent) or more than one non-steroidal anti-inflammatory drug

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IPI-145, low dose BID<br> | Drug: IPI-145<br>* 2 blinded capsules will be administered twice a day (morning and night) for 12 weeks.<br>|
| Experimental: IPI-145, medium dose BID<br> | Drug: IPI-145<br>* 2 blinded capsules will be administered twice a day (morning and night) for 12 weeks.<br>|
| Experimental: IPI-145, high dose BID<br> | Drug: IPI-145<br>* 2 blinded capsules will be administered twice a day (morning and night) for 12 weeks.<br>|
| Placebo Comparator: Placebo BID<br> | Drug: Placebo<br>* 2 blinded capsules will be administered twice a day (morning and night) for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who achieve a 20% improvement in the American College of Rheumatology Criteria (ACR20) from Baseline to Week 12 |  | Baseline (Day 1), Weeks 2, 4, 6, 8, 10 and 12 |