Long-term Follow-up Study of GLPG0634 in Active Rheumatoid Arthritis Participants

Phase 2CompletedNCT02065700

Lakefront Biotherapeutics NV739 enrolled

Overview

The primary objective of the study was to evaluate the long-term safety and tolerability of filgotinib (formerly GLPG0634) for the treatment of rheumatoid arthritis. Participants were enrolled in this open-label long-term follow-up study after they had completed one of the two core studies, GLPG0634-CL-203 (DARWIN1) (NCT01888874) or GLPG0634-CL-204 (DARWIN2) (NCT01894516), and were evaluated for any side effects that might have occured (long-term safety and tolerability) when taking filgotinib. During the course of the study, participants were also examined for long-term effects of filgotinib administration on disease activity (efficacy), participant's disability, fatigue, and quality of life.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

739

Conditions

Rheumatoid Arthritis

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Participants who completed one of the qualifying core studies GLPG0634-CL-203 or GLPG0634-CL-204 and may benefit from filgotinib long-term treatment according to the Investigator's judgment * Females of childbearing potential and sexually active men must agree to use highly effective method of birth control as specified in the protocol, during the study and for at least 12 weeks after the last dose of filgotinib Key Exclusion Criteria: * Participants who prematurely withdrew from one of the 2 core studies (GLPG0634-CL-203 or GLPG0634-CL-204), for any reason * Persistent abnormal lab values during one of the 2 core studies (GLPG0634-CL-203 or GLPG0634-CL-204), according to the Investigator's judgment * Diagnosis of rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid arthritis, except for secondary Sjogren's syndrome * Any condition or circumstances which, in the opinion of the Investigator, may make a participant unlikely or unable to complete the study or comply with study procedures and requirements Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (111)

Arthro, Arthritis Care & Research

Gilbert, Arizona, United States

Arizona Arthritis & Rheumatology Research PLLC

Mesa, Arizona, United States

C.V. Mehta MD Medical Corp.

Hemet, California, United States

Desert Medical Advances

Palm Desert, California, United States

RASF Clinical Research Center

Boca Raton, Florida, United States

Outcomes

Primary Outcomes

Number of Participants Experiencing Treatment-Emergent Adverse Events

An Adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. Treatment-emergent adverse events (TEAEs) were defined as any AEs with an onset date on or after the filgotinib start date in the core studies or GLPG0634-CL-205 (NCT02065700), and no later than 30 days after permanent discontinuation of filgotinib in GLPG0634-CL-205 (NCT02065700) or of either 30 days after the last dose date.

Time frame: From First dose to Week 437

Secondary Outcomes

Percentage of Participants Achieving American College of Rheumatology (ACR) 20 Response: Non-Responder Imputation (NRI)

The American College of Rheumatology (ACR) response was a measurement of improvement in multiple disease assessment criteria. The ACR20 response was defined as: 1) ≥ 20% improvement from baseline in swollen joint count 66 (SJC66), and 2) ≥ 20% improvement from baseline in tender joint count 68 (TJC68), and 3) ≥ 20% improvement from baseline in at least 3 of the following 5 items: 1. Pain visual analog scale (VAS) (taken from the Health Assessment Questionnaire - Disability Index \[HAQ-DI\]), 2.Subject's Global Assessment of Disease Activity (SGA) (VAS), 3. Physician's Global Assessment of Disease Activity (PGA) (VAS), 4. Total HAQ-DI score, and 5. High-Sensitivity C- Reactive Protein (hsCRP).

Time frame: Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408

Percentage of Participants Achieving ACR20 Response: Observed Case (OC)

The ACR response was a measurement of improvement in multiple disease assessment criteria. The ACR20 response was defined as: 1) ≥ 20% improvement from baseline in SJC66, and 2) ≥ 20% improvement from baseline in tender TJC68, and 3) ≥ 20% improvement from baseline in at least 3 of the following 5 items: 1. Pain VAS (taken from the HAQ-DI), 2.SGA (VAS), 3. PGA (VAS), 4. Total HAQ-DI score, and 5. hsCRP.

Time frame: Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408

Percentage of Participants Achieving ACR50 Response: NRI

The ACR response was a measurement of improvement in multiple disease assessment criteria. ACR50 response was defined as: 1) ≥ 50% improvement from baseline in SJC66, and 2) ≥ 50% improvement from baseline in TJC68, and 3) ≥ 50% improvement from baseline in at least 3 of the following 5 items: 1. Pain VAS (taken from the HAQ-DI) 2.SGA (VAS) 3. PGA (VAS) 4. Total HAQ-DI score 5. hsCRP.

Time frame: Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408

Percentage of Participants Achieving ACR50 Response: OC

Time frame: Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408

Percentage of Participants Achieving ACR70 Response: NRI

The ACR response was a measurement of improvement in multiple disease assessment criteria. ACR70 response was defined as : 1) ≥ 70% improvement from baseline in SJC66, and 2) ≥ 70% improvement from baseline in TJC68, and 3) ≥ 70% improvement from baseline in at least 3 of the following 5 items: 1. Pain VAS (taken from the HAQ-DI), 2.SGA (VAS), 3. PGA (VAS), 4. Total HAQ-DI score, and 5. hsCRP.

Time frame: Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408

Percentage of Participants Achieving ACR70 Response: OC

Time frame: Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408

ACR N% Improvement (ACR-N) Response: OC

ACR-N was defined as the smallest percentage improvement from core baseline in SJC66, TJC68 and the median of the following 5 items (Pain VAS \[taken from the HAQ-DI\], 2.SGA (VAS), 3. PGA (VAS), 4. Total HAQ-DI score, and 5. hsCRP). It had a range between 0 and 100%.

Time frame: Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408

Change From Core Baseline in Disease Activity Score Based on 28 Joints Using C-reactive Protein (DAS28[CRP]): OC

The DAS28(CRP) was a measure of the participant's disease activity calculated using the TJC (28 joints), SJC (28 joints), SGA \[using a VAS on a scale of 0 (very well) to 100 (very poor)\] and hsCRP using the formula: DAS28(CRP) = 0.56 \* Square root \[SQRT\] (TJC28) + 0.28 \* SQRT(SJC28) + 0.36 \* Ln(CRP+1) + 0.014 \* SGA + 0.96 and the total possible score ranged from 1 to 9.4. Higher values indicated higher disease activity. A negative change from baseline indicated improvement.

Time frame: Core Baseline, Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408

Change From Core Baseline in Simple Disease Activity Index (SDAI): OC

SDAI score consisted of following parameters: TJC (28 joints), SJC (28 joints), SGA (0 to 10 cm), PGA (0 to 10 cm), CRP (mg/dL). SDAI = TJC + SJC + SGA + PGA+ CRP. The SDAI score ranged from 0 to approximately 86. Higher SDAI indicated greater disease activity. A negative change from baseline indicated improvement.

Change From Core Baseline in Clinical Disease Activity Index (CDAI): OC

The CDAI was the SDAI modified that excluded CRP and consisted of following parameters: TJC (28 joints), SJC (28 joints), SGA (0 to 10 cm), PGA (0 to 10 cm). SDAI = TJC + SJC + SGA+ PGA. The CDAI score ranged from 0 to approximately 76. Higher CDAI indicated greater disease activity. A negative change from baseline indicated improvement.

Percentage of Participants Achieving European League Against Rheumatism (EULAR) Response: OC

DAS28(CRP) was categorized into EULAR response categories (none, moderate, good) as follows: None= Actual DAS28(CRP) ≤ 3.2, \> 3.2 to ≤ 5.1, or \> 5.1 AND Improvement in DAS28(CRP) from baseline ≤ 6.0 or \> 0.6 to ≤ 1.2; Moderate= Actual DAS28(CRP) ≤ 3.2 AND Improvement in DAS28(CRP) from baseline \> 0.6 to ≤ 1.2, Actual DAS28(CRP) \> 3.2 to ≤ 5.1 or \> 5.1 AND Improvement in DAS28(CRP) from baseline \> 1.2, or Actual DAS28(CRP) \> 3.2 to ≤ 5.1 AND Improvement in DAS28(CRP) from baseline \> 0.6 to ≤ 1.2; Good= Actual DAS28(CRP) ≤ 3.2 AND Improvement in DAS28(CRP) from baseline \> 1.2.

Percentage of Participants Achieving ACR/EULAR Remission: NRI

A participant's disease activity status was defined as being in remission when scores on the TJC28, SJC28, CRP (actual value in mg/dL) and SGA (cm) were all ≤ 1.

Time frame: Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408

Percentage of Participants Achieving ACR/EULAR Remission: OC

A participant's disease activity status was defined as being in remission when scores on the TJC28, SJC28, CRP (actual value in mg/dL) and SGA (cm) were all ≤ 1.

Time frame: Extension Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, 312, 324, 336, 348, 360, 372, 384, 396, 408

Change From Core Baseline in Physical Component Score (PCS) of Quality of Life Using the Short Form-36 (SF-36) Scores: OC

The health-related quality of life of the subject was assessed using the SF-36 with a 4-week recall period. This consists of 36 questions belonging to 8 domains in 2 components: * Physical well-being: 4 domains: physical functioning (10 items), role physical (4 items), bodily pain (2 items), and general health (GH) perceptions (5 items). * Mental well-being: 4 domains: vitality (4 items), social functioning (2 items), role emotional (3 items), and mental health (5 items). These scales were from 0 to 100 with higher scores indicating a better quality of life.

Time frame: Core Baseline, Extension Baseline, Weeks 48, 96, 144, 192, 240, 288, 336, 384

Change From Core Baseline in MCS of Quality of Life Using the SF-36 Scores: OC

Time frame: Core Baseline, Extension Baseline, Weeks 48, 96, 144, 192, 240, 288, 336, 384

Change From Core Baseline in Quality of Life Using Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale: OC

FACIT-Fatigue scale was a 13-item questionnaire, each scored on a 5-point scale: 0 (Not at all) to 4 (Very much). Negatively stated items were reversed by subtracting the response from "4" before being added to obtain a total score. The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score), with a higher score indicating less fatigue. A positive change from baseline indicated better quality of life.

Time frame: Core Baseline, Extension Baseline, Weeks 48, 96, 144, 192, 240, 288, 336, 384