Study to Evaluate Safety and Pharmacokinetics of GS-4059 (Tirabrutinib) in Healthy Volunteers and Participants With Rheumatoid Arthritis (RA)

NCT ID: NCT02626026

Last Updated: 2020-09-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-26
• Study Completion Date: 2016-09-01

Brief Summary

This study will consist of two parts: Part A will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of tirabrutinib in healthy participants. Part B will evaluate the safety, tolerability, and the effect of tirabrutinib on disease-specific clinical markers and outcomes in participants with rheumatoid arthritis (RA).

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Cohort 1, Part A: Tirabrutinib 20 mg QD

Tirabrutinib 20 mg capsules orally once daily (QD) in the morning for 1 week.

Group Type: EXPERIMENTAL

Tirabrutinib

Intervention Type: DRUG

Capsules administered orally.

Cohort 1, Part A: Placebo

Placebo to match tirabrutinib capsules orally QD in the morning for 1 week.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Capsules administered orally.

Cohort 2, Part A: Tirabrutinib 10 mg BID

Tirabrutinib 10 mg capsules orally twice daily (BID) (morning and approximately 12 hours later) for 7 days. On Day 7, only morning dose was administered.

Group Type: EXPERIMENTAL

Tirabrutinib

Intervention Type: DRUG

Capsules administered orally.

Cohort 2, Part A: Placebo

Placebo to match tirabrutinib capsules orally BID (morning and approximately 12 hours later) for 7 days. On Day 7, only morning dose was administered.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Capsules administered orally.

Part B: Tirabrutinib 20 mg QD

Tirabrutinib 20 mg capsules orally QD for 4 weeks.

Group Type: EXPERIMENTAL

Tirabrutinib

Intervention Type: DRUG

Capsules administered orally.

Part B: Placebo

Placebo to match tirabrutinib capsules orally QD for 4 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Capsules administered orally.

Interventions

Tirabrutinib

Capsules administered orally.

Intervention Type: DRUG

Placebo

Capsules administered orally.

Intervention Type: DRUG

Other Intervention Names

GS-4059

Eligibility Criteria

Inclusion Criteria

Part A

• Be a nonsmoker
• Have a calculated body mass index (BMI) from 19 to 30 kg/m^2, inclusive, at screening
• Have a creatinine clearance (CrCl) ≥ 90 mL/min (using the Cockcroft-Gault method based on serum creatinine and actual body weight as measured at screening
• Females of childbearing potential must have a negative serum pregnancy test at screening and clinic admission.
• Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
• Must, in the opinion of the investigator, be in good health based upon medical history and physical examination, including vital signs
• Screening laboratory evaluations (hematology including reticulocytes, fasting lipids, chemistry, and urinalysis) must fall within the normal range of the local laboratory's reference ranges unless the results have been determined by the investigator to have no clinical significance
• Have either a normal 12-lead ECG or one with abnormalities that are considered clinically insignificant by the investigator in consultation with the Sponsor

Part B

• Diagnosis of RA (according to the 1987 American College of Rheumatology (ACR) classification criteria OR a score of ≥ 6 as defined by the ACR/European League Against Rheumatism Classification and Diagnostic Criteria for RA)
• Individuals must have taken methotrexate (MTX) 7.5 to 25 mg/week continuously for at least 12 weeks, with at least 6 weeks of stable dose prior to first study drug dose and throughout study duration.
• Individuals must be receiving folic or folinic acid supplementation at a stable dose for at least 6 weeks prior to Day 1 dosing and throughout study duration
• Individuals are allowed to remain on anti-malarial therapy, with at least 8 weeks of stable dose prior to first study drug dose
• Use of oral corticosteroids of no more than 10 mg prednisone or its equivalent per day is allowed if dose is stable for at least 28 days prior to first study drug dose
• Nonsteroidal anti-inflammatory drugs (NSAIDs) or other analgesics (including aspirin ≤ 100 mg daily) are allowed if doses are stable for at least 14 days prior to the first dose of study drug
• Estimated creatinine clearance (CLCr) ≥ 60 mL/min (using the Cockcroft-Gault method) based on serum creatinine and actual body weight as measured at the screening evaluation
• White blood cells (WBC), neutrophil count, lymphocyte count, and platelet count ≥ 0.75 x lower limit of normal (LLN)
• A negative serum pregnancy test at screening and a negative pregnancy test on the Day 1 visit prior to the first dose of study drug for female individual of child bearing potential.
• Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception

Exclusion Criteria

Part A

• Pregnant or lactating individuals
• Have any serious or active medical or psychiatric illness (including depression) which, in the opinion of the Investigator, would interfere with individual's treatment, assessment, or compliance with the protocol. This would include renal, cardiac, hematological, hepatic, pulmonary (including chronic asthma), endocrine (including diabetes), central nervous, gastrointestinal (including an ulcer), vascular, metabolic (thyroid disorders, adrenal disease), immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment
• Positive test for drugs of abuse, including alcohol at screening or on Day -1/check-in
• A positive test result for human immunodeficiency virus (HIV-1) antibody, hepatitis B (HBV) surface antigen or hepatitis C (HCV) antibody
• Have poor venous access that limits phlebotomy
• Have taken any prescription medications or over-the-counter medications, including herbal products, within 28 days prior to start of study drug dosing, with the exception of vitamins and/or acetaminophen and/or hormonal contraceptive medications
• Have been treated with systemic steroids, immunosuppressant therapies, or chemotherapeutic agents within 3 months prior to Screening or expected to receive these agents during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies)
• Significant drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity)
• Medical or surgical treatment that permanently alters gastric absorption (eg, gastric or intestinal surgery); a history of cholecystectomy is not exclusionary

Part B

• Known hypersensitivity to formulation excipient.
• Pregnant or lactating females
• Previous treatment with B-cell depleting agents (eg, rituximab) within 12 months of treatment
• Prior treatment with any commercially available or investigational Bruton's tyrosine kinase (BTK) inhibitor
• Diagnosis of diabetes, history of impaired glucose tolerance test, history of abnormal glycated haemoglobin (HbA1c), or history of impaired fasting glucose
• Current treatment with any other disease modifying anti-rheumatic drug (DMARD) other than MTX and hydroxychloroquine, unless appropriate wash out
• Current treatment with any biologic agent, unless appropriate wash out
• Any laboratory abnormality or condition that, in the investigator's opinion, could adversely affect the safety of the individual or impair the assessment of study results
• History of or current inflammatory joint disease, other than RA
• Active significant systemic involvement secondary to RA such as vasculitis, pulmonary fibrosis or Felty's syndrome
• History of or current autoimmune or rheumatic disorders, other than RA
• RA functional class 4 or other uncontrolled medical conditions
• History of ongoing, chronic or recurrent infections or recent serious or life-threatening infection
• Presence of any condition that could, in the opinion of the investigator, compromise the individual's ability to participate in the study, such as history of substance abuse, alcoholism, or a psychiatric condition

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ono Pharmaceutical Co. Ltd

INDUSTRY

Sponsor Role: collaborator

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

UC Davis Lawrence J. Ellison

Sacramento, California, United States

SeaView Research, Inc.

Miami, Florida, United States

Omega Research Consultants, LLC

Orlando, Florida, United States

Lovelace Scientific Resources, Inc.

Venice, Florida, United States

Center for Arthritis & Osteoporosis

Elizabethtown, Kentucky, United States

Justus J. Fiechtner, M.D., P.C.

Lansing, Michigan, United States

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

Clinical Research Center of Reading, LLC

Wyomissing, Pennsylvania, United States

Arthritis & Osteoporosis Center of South Texas

San Antonio, Texas, United States

Countries

United States

Other Identifiers

2015-003240-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-407-1833

Identifier Type: -

Identifier Source: org_study_id