Filgotinib in Combination With Methotrexate in Adults With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2016-000568-41-CZ
• Date of registration: 21/10/2016
• Prospective Registration: Yes
• Primary sponsor: Gilead Sciences, Inc.
• Public title: Filgotinib in Combination With Methotrexate in Adults With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate
• Scientific title: A Randomized, Double-blind, Placebo- and Active-controlled, Multicenter, Phase 3 Study to Assess the Efficacy and Safety of Filgotinib Administered for 52 weeks in Combination with Methotrexate to Subjects with Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate
• Date of first enrolment: 05/01/2017
• Target sample size: 1650
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000568-41
• 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: yes; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• 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, Brazil, Bulgaria, Canada, Chile, Colombia, Czech Republic, France, Germany, Hong Kong, Hungary, India, Ireland, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, New Zealand, Peru, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Switzerland, Taiwan, Thailand, Ukraine, 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) Must meet at least one of the Screening parameters defined in the protocol (section 4.2) regarding the number of joint erosions and serum CRP
5) Ongoing treatment with a stable dose of MTX as described in the protocol (section 4.2)
6) Females of childbearing potential must have a negative pregnancy test at screening and Day 1
7) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception.
8) Lactating female subjects must agree to discontinue nursing from Screening through the end of their study participation.
9) Meet one of the tuberculosis (TB) Screening criteria described in the protocol (section 4.2)
10) Able and willing to sign the informed consent as approved by the Independent Ethics Committee (IEC)/Institutional Review Board (IRB). Written consent must be provided before initiating any screening evaluations. Subjects must have read and understood the informed consent form (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.
11) Able and willing to perform subcutaneous self-injections or have a caregiver able, willing and available to administer the injections.
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 825
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 825

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 (or 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 (NSAIDs) which have not been at a stable dose (defined as no change in prescription) for at least 2 weeks prior to Day 1. NOTE: subjects are permitted to take acetylsalicylic acid at a dose of =325mg daily for cardiac prophylaxis, or occasional NSAIDs for non-RA indications (eg, headache).
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
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 anesthesia) within the last 3 months 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 that would interfere with assessment of study parameters or increase risk to the subject by participating in the study.
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, 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
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 (HBV) infection.
21) History of opportunistic infection, or immunodeficiency syndrome, which would put the subject at risk, as per investigator judgment.
22) Active infection that is clinically significant, as per judgment of the investigator, or any infection requiring hospitalization or treatment with intravenous anti-infectives within 60 days of Screening; or any infection requiring oral anti-infective therapy within 30 days of Screening.
23) Currently on any therapy for chronic infection. Past history of disseminat

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

Health Condition(s) or Problem(s) studied

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

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

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

Trade Name: Humira (adalimumab) 40 mg s.c. injection
Product Name: Adalimumab
Pharmaceutical Form: Injection
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Other descriptive name: Humira
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Injection
Route of administration of the placebo: Subcutaneous 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

Trade Name: Humira (adalimumab) 40mg in 0.4 ml s.c. injection
Product Name: Adalimumab
Pharmaceutical Form: Injection
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

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

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

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: - To evaluate the effects of filgotinib versus placebo 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 Questionnaire Disability Index (HAQ-DI) score at Week 12
- 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 DAS28 (CRP)<2.6 at Week 24
- To evaluate the effects of filgotinib versus placebo on preservation of joint structure as measured by change from Baseline in the van der Heijde modified Total Sharp Score (mTSS) at Week 24
- To evaluate the effects of filgotinib versus adalimumab for the treatment of signs and symptoms of RA as measured by the proportion of subjects achieving DAS28 (CRP) = 3.2 at Week 12

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 12 and Week 24

Secondary end point(s): The key secondary endpoints for this study 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
- The proportion of subjects who achieve DAS28 (CRP)<2.6 at Week 24
- Change from Baseline in mTSS at Week 24

Secondary ID(s)

2016-000568-41-SK

GS-US-417-0301

Source(s) of Monetary Support

Gilead Sciences, Inc.

Ethics review

Status: Approved
Approval date:
Contact: