Study to Evaluate Efficacy, Safety and Tolerability of JTE-051 in Subjects With Active Rheumatoid Arthritis

Phase 2

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Drug: Placebo; Drug: JTE-051

• Registration Number: NCT02919475
• Lead Sponsor: Akros Pharma Inc.

Brief Summary

This study will evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of JTE-051 administered for 12 weeks in subjects with active rheumatoid arthritis who are receiving background non-biologic disease-modifying anti-rheumatic drug therapy.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-09-14
• Study First Submitted: 2016-09-27
• Study First Submitted QC: 2016-09-28
• Study First Posted: 2016-09-29
• Primary Completion: 2018-06-25
• Study Completion: 2018-06-25
• Disposition First Submitted: 2019-11-06
• Disposition First Submitted QC: 2019-11-08
• Disposition First Posted: 2019-11-12
• Results First Submitted: 2021-03-25
• Status Verified: 2021-06
• Results First Submitted QC: 2021-06-11
• Last Update Submitted: 2021-06-11
• Results First Posted: 2021-06-14
• Last Update Posted: 2021-06-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 260

Inclusion Criteria

• A diagnosis of RA prior to the Screening Visit.
• Active disease despite ongoing therapy with up to two non-biologic disease-modifying anti-rheumatic drugs, including methotrexate at both the Screening and Baseline Visits.
• Screening hs-CRP ≥1.2 x upper limit of normal (ULN).

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Exclusion Criteria

• Prior/current exposure to biologic and/or kinase inhibitor therapy.
• Known history or presence of polyneuropathy of any cause and no presence of clinically active compression neuropathy, radiculopathy or plexopathy at the Screening Visit.
• Positive test results for human immunodeficiency (HIV) virus, hepatitis B virus or hepatitis C (HCV) virus at the Screening Visit.
• Positive drug of abuse and alcohol test results.
• History of a clinically-significant infection that required oral antimicrobial or antiviral therapy within 8 weeks prior to Day 1.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	One dose of study drug by mouth daily for 12 weeks
JTE-051 Dose 2	JTE-051	One dose of study drug by mouth daily for 12 weeks
JTE-051 Dose 3	JTE-051	One dose of study drug by mouth daily for 12 weeks
JTE-051 Dose 4	JTE-051	One dose of study drug by mouth daily for 12 weeks
JTE-051 Dose 1	JTE-051	One dose of study drug by mouth daily for 12 weeks

Primary Outcome Measures

Name	Time	Method
Percentage of Subjects Achieving at Least 20% Improvement From Baseline in American College of Rheumatology (ACR) Core Set Measures (ACR20 Response Rate) Compared to Placebo at End-of-treatment (EOT)	Up to 12 Weeks	Percentage of subjects achieving at least 20% improvement from baseline (ACR20) in tender and swollen joint counts (ACR core set measures 1 and 2) and at least 20% improvement from baseline in the 3 of the 5 remaining ACR core set measures at EOT (up to Week 12) compared to placebo.; The ACR core set measures are: 1. Tender joint count; 2. Swollen joint count; 3. Subject Assessment of arthritis pain; 4. Subject's Global Assessment of disease activity (SGA); 5. Physician's Global Assessment of disease activity (PGA); 6. Health Assessment Questionnaire Disability Index (HAQ-DI); 7. Acute Phase Reactant (i.e., hs-CRP - high sensitivity C-reactive protein)

Secondary Outcome Measures

Name	Time	Method
Percentage of Subjects Achieving ACR70 Response Rate Compared to Placebo at Week 12	Week 12	Percentage of subjects achieving at least 70% improvement from baseline (ACR70) in tender and swollen joint counts (ACR core set measures 1 and 2) and at least 70% improvement from baseline in the 3 of the 5 remaining ACR core set measures at Week 12 compared to placebo.; The ACR core set measures are: 1. Tender joint count; 2. Swollen joint count; 3. Subject Assessment of arthritis pain; 4. Subject's Global Assessment of disease activity (SGA); 5. Physician's Global Assessment of disease activity (PGA); 6. Health Assessment Questionnaire Disability Index (HAQ-DI); 7. Acute Phase Reactant (i.e., hs-CRP - high sensitivity C-reactive protein)
Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 12	Week 12	The SDAI Scores indicate how active a patient's rheumatoid arthritis (RA) is currently. The SDAI is the sum of 5 outcome parameters: tender joint score (0 to 28), swollen joint score (0 to 28), Patient's Global Score of disease activity (0 to 10), Physician's Global Score of disease activity (0 to 10) and C-reactive protein (CRP, 0 to 10).General SDAI Score Interpretation is as follows: 0.0 - 3.3 Remission 3.4 - 11.0 Low Activity 11.1 - 26.0 Moderate Activity 26.1 - 86.0 High Activity
Trough Concentrations (Ctrough) of JTE-051 in Plasma at Week 12	Week 12
Percentage of Subjects Achieving ACR20 Response Rate Compared to Placebo at Week 12	Week 12	Percentage of subjects achieving at least 20% improvement from baseline (ACR20) in tender and swollen joint counts (ACR core set measures 1 and 2) and at least 20% improvement from baseline in the 3 of the 5 remaining ACR core set measures at Week 12 compared to placebo.; The ACR core set measures are: 1. Tender joint count; 2. Swollen joint count; 3. Subject Assessment of arthritis pain; 4. Subject's Global Assessment of disease activity (SGA); 5. Physician's Global Assessment of disease activity (PGA); 6. Health Assessment Questionnaire Disability Index (HAQ-DI); 7. Acute Phase Reactant (i.e., hs-CRP - high sensitivity C-reactive protein)
Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 12	Week 12	The CDAI is a useful clinical composite score for following patients with rheumatoid arthritis (RA). The CDAI is the sum of 4 outcome parameters: tender joint score (0 to 28), swollen joint score (0 to 28), Patient's Global Score of disease activity (0 to 10) and Physician's Global Score of disease activity (0 to 10). The CDAI Score Interpretation is as follows: 0 to 2.8: Remission 2.9 to 10: Low Disease Activity 10.1 to 22: Moderate Disease Activity 22.1 to 76: High Disease Activity
Percentage of Subjects Achieving ACR50 Response Rate Compared to Placebo at Week 12	Week 12	Percentage of subjects achieving at least 50% improvement from baseline (ACR50) in tender and swollen joint counts (ACR core set measures 1 and 2) and at least 50% improvement from baseline in the 3 of the 5 remaining ACR core set measures at Week 12 compared to placebo.; The ACR core set measures are: 1. Tender joint count; 2. Swollen joint count; 3. Subject Assessment of arthritis pain; 4. Subject's Global Assessment of disease activity (SGA); 5. Physician's Global Assessment of disease activity (PGA); 6. Health Assessment Questionnaire Disability Index (HAQ-DI); 7. Acute Phase Reactant (i.e., hs-CRP - high sensitivity C-reactive protein)
Change From Baseline in DAS28-CRP (Disease Activity Score [DAS] Based on High-sensitivity C-reactive Protein [Hs-CRP]) at Week 12	Week 12	Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consists of composite score of following variables: 28 tender joint count (TJC28) ranging from 0 to 28, 28 swollen joint count (SJC28) ranged from 0 to 28, C-reactive protein (CRP) (milligrams per liter) and subject's global assessment of disease activity (SGA) ranging from 0 (no disease activity) to 10 (extremely active disease). DAS28-CRP was calculated using following formula: DAS28-CRP=0.56\*square root (sqrt)(TJC28)+0.28\*sqrt(SJC28)+0.36\*natural log(CRP+1)+0.014\*SGA+0.96.; DAS28-CRP ranged from 0.96-9.4, where lower scores indicated less disease activity and remission is DAS28-CRP \<2.6.; A decrease in DAS28-CRP indicated an improvement in participant's condition.
Change From Baseline in HAQ-DI (Health Assessment Questionnaire Disability Index) at Week 12	Week 12	The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty \[0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)\] in 8 functional area categories: (1) dressing and grooming; (2) arising; (3) eating; (4) walking; (5) hygiene; (6) reaching; (7) gripping; and (8) performing other daily activities. Scores from each functional area category (total 8 categories) were averaged to calculate the HAQ-DI score, which ranged from 0 (no disability) to 3 (severe disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.
Number of Subjects With Treatment-related Adverse Events	Up to 16 Weeks	Subjects in the Safety Population (258, subjects who were randomly assigned to treatment and who received at least one dose of study drug). The number of subjects in the Safety Population is 258 subjects, which is 1 less than the Randomized Population of 259 subjects, since 1 randomized subject did not receive any study drug.