Filgotinib in Combination With Conventional Anti-rheumatic Drugs in Adults With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Biologic DMARD treatment.

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2016-000569-21-GB
• Date of registration: 01/11/2016
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: Filgotinib in Combination With Conventional Anti-rheumatic Drugs in Adults With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Biologic DMARD treatment.
• Scientific title: A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 3 Study to Assess the Efficacy and Safety of Filgotinib Administered for 24 weeks in Combination with Conventional Synthetic Disease-modifying Anti-rheumatic Drug(s) (csDMARDs) to Subjects with Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Biologic DMARD(s) Treatment
• Date of first enrolment: 23/12/2016
• Target sample size: 423
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000569-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

• Name: Clinical Trials Mailbox
• Affiliation: Gilead Sciences International Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
For a complete list of study inclusion criteria, please refer to study protocol (Sections 4.2):
1) Male or female subjects who are =18 years of age, on the day of signing informed consent.
2) Have a diagnosis of RA (2010 ACR/EULAR criteria for RA), and are ACR functional class I-III.
3) Have =6 swollen joints (from a SJC66) and =6 tender joints (from a TJC68) at both screening and Day 1 (need not be the same joints)
4) Have serum CRP = 4 mg/L.
5) Ongoing treatment with a stable prescription of 1 or 2 permitted csDMARD(s) as described in the study protocol (section 4.2)
6) Have received at least one bDMARD for the treatment of RA to which they have had an inadequate response or intolerance. An inadequate response is defined as documented continued or recurrent disease activity after at least 12 weeks of treatment with any investigational or licensed bDMARD, including biosimilars, for the treatment of RA. Intolerance is defined as any documented adverse effect associated with a bDMARD used
according to its respective label. There is no limit to the prior number of bDMARDs that may have been used by the subject, however, the subject must not be on a bDMARD at Day 1 (appropriate wash out needs to be satisfied according to the protocol) or during the study.
7) Females of childbearing potential (defined in protocol Appendix 5) must have a negative pregnancy test at screening and Day 1
8) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception.
9) Lactating female subjects must agree to discontinue nursing from Screening through the end of their study participation
10) Meet one of the tuberculosis (TB) Screening criteria described in the protocol (section 4.2)
11) Able and willing to sign the informed consent as approved by the IRB/IEC. Written consent must be provided before initiating any screening evaluations. Subjects must have read and understood the ICF, must fully understand the requirements of the study, and must be willing to comply with all study visits and assessments subjects who cannot read or understand the ICF may not be enrolled by a guardian or any other individual.
12) Subjects receiving non-prohibited medication for any reason should be on a stable dose (defined as no change in prescription) within 7 days or 5 half-lives (whichever is longer) prior to the first administration of study drug on Day 1.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 211
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 211

Exclusion criteria:
For a complete list of study exclusion criteria, please refer to study protocol (Sections 4.3):
1) Prior treatments for RA as defined in Section 4.3 of the protocol
2) Known hypersensitivity or allergy to the study drug(s), its metabolites, or formulation excipients.
3) Oral steroids at a dose >10 mg/day of prednisone equivalent or a prescription for oral steroids which has changed within 4 weeks of Day 1.
4) Receipt of an intra-articular or parenteral corticosteroid injection within 4 weeks prior to Day 1.
5) Use of nonsteroidal anti-inflammatory drugs (NSAID(s) which have not been at a stable dose (defined as no change in prescription) for at least 2 weeks prior to Day 1.
6) Administration of a live/ attenuated vaccine within 30 days prior to Day 1, or planned during the study.
7) Participation in any clinical study of an investigational drug/device within 4 weeks or 5 half-lives prior to Screening, whichever is longer. Exposure to investigational biologics should be discussed with the sponsor.
8) Have undergone surgical treatments for RA including synovectomy or arthroplasty in >4 joints and/or within the last 12 weeks prior to Screening
9) Have any chronic, uncontrolled medical condition, which would put the subject at increased risk during study participation, such as uncontrolled: diabetes, hypertension, morbid obesity, thyroid, adrenal, pulmonary, hepatic, renal, neurologic or psychiatric disease, or other disease of concern, as per judgment of investigator
10) Have a history of major surgery (requiring regional block or general anaesthesia) within the last 12 weeks prior to Screening or planned major surgery during the study.
11) Have a moderately to severely active, generalized musculoskeletal disorder that would interfere with assessment of study parameters or increase risk to the subject by participating in the study
12) Active autoimmune disease other than those listed above, that would interfere with assessment of study parameters or increase risk to the subject by participating in the study, eg, inflammatory bowel disease, uncontrolled thyroiditis, systemic vasculitis, transverse myelitis or uveitis.
13) History of or current moderate to severe congestive heart failure (New York Heart Association [NYHA] class III or IV), or within the last 6 months, a cerebrovascular accident, myocardial infarction, unstable angina, unstable arrhythmia or new or significant ECG finding at Screening, or any other cardiovascular condition which, in the opinion of the investigator, would put the subject at risk by participation in the study.
14) History of malignancy within the past 5 years prior to Screening (except for adequately treated basal cell carcinoma or non-metastatic squamous cell carcinoma of the skin or cervical carcinoma in situ with no evidence of recurrence).
15) History of lymphoproliferative disease or current lymphoproliferative disease.
16) History of gastrointestinal perforation.
17) History of organ or bone marrow transplant.
18) Positive serology for human immunodeficiency virus (HIV) 1 or 2
19) Evidence of active Hepatitis C Virus (HCV) infection
20) Evidence of active Hepatitis B Virus (

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Moderately to severely active rheumatoid arthritis
MedDRA version: 20.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Product Name: Filgotinib
Product Code: GS-6034
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: FILGOTINIB
Other descriptive name: FILGOTINIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Filgotinib
Product Code: GS-6034
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: FILGOTINIB
Other descriptive name: FILGOTINIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective of this study is to evaluate the effects of filgotinib versus placebo for the treatment of signs and symptoms of rheumatoid arthritis (RA) as measured by the proportion of subjects achieving an American College of Rheumatology 20% improvement response (ACR20) at Week 12

Secondary Objective: The secondary objectives of this study are:
- To evaluate the effects of filgotinib versus placebo for the treatment of signs and symptoms of RA as measured by the proportion of subjects achieving Disease Activity Score for 28 joint count using c-reactive protein (DAS28 [CRP])=3.2 at Week 12
- To evaluate the effect of filgotinib versus placebo on physical function as measured by change from Baseline in the Health Assessment Questionaire Disability Index (HAQ-DI) at Week 12
- To evaluate the safety and tolerability of filgotinib
- To evaluate the effects of filgotinib on work productivity, fatigue, and general quality of life as measured by SF-36, FACIT-Fatigue, EQ-5 and WPAI-RA.

Primary end point(s): The primary endpoint is the proportion of subjects who achieve an ACR20 response at Week 12.

Timepoint(s) of evaluation of this end point: Week 12

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 12

Secondary end point(s): The key secondary endpoints are:
- The proportion of subjects who achieve DAS28 (CRP)=3.2 at Week 12
- Change from Baseline in the HAQ-DI score at Week 12

Secondary ID(s)

GS-US-417-0302

2016-000569-21-BE

Source(s) of Monetary Support

Gilead Sciences, Inc.

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 04/07/2019
• Date Completed: 26/06/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-000569-21/results