Study of GS-0151 in Participants With Rheumatoid Arthritis

Key Inclusion Criteria:

Medical History/Physical Characteristics; All Cohorts:

• Individuals must not be on a biologic disease-modifying antirheumatic drug (b/tsDMARD) on Day 1 and must have discontinued all b/tsDMARDs (includingbiosimilars and generics) at least 4 weeks prior to Day 1 with the exception of Bcell-depleting agents (eg, rituximab), which must be discontinued for at least 6months prior to Day 1.

• Ongoing treatment with at least 1 but no more than 2 protocol-permitted conventionalsynthetic disease-modifying antirheumatic drug (csDMARDs) for at least 12 weeks, ata stable dose for at least 6 weeks prior to Day 1 and remain stable throughout thetreatment period:

1. Use of oral, intramuscular (IM), or subcutaneous(ly) (SC) methotrexate 7.5 to 25 mg/week. Individuals on methotrexate must be receiving folic or folinic acidsupplementation at a stable dose.

2. Oral hydroxychloroquine ≤ 400 mg/day or chloroquine ≤ 250 mg/day.

3. Oral sulfasalazine 1 to 3 g/day.

4. Oral leflunomide 10 to 20 mg/day.

• Use of oral corticosteroids of no more than 10 mg prednisone or equivalent per dayis allowed if the dose is stable for at least 14 days prior to Day 1. Inhaledcorticosteroids for stable medical conditions are allowed but must have been at astable dose for at least

1 week prior to the first dose of study drug. Occasional topical corticosteroids arepermitted.

• Where nonsteroidal anti-inflammatory drug (NSAIDs) or acetaminophen are used, thedose must be stable for at least 1 week prior to Day 1

• Individuals must have discontinued all high-potency opiates at least 1 week prior toDay 1.

Cohort 3 Only:

• Individuals must meet all of the following cohort-specific inclusion criteria, inaddition to meeting the inclusion criteria for all individuals , to be eligible forparticipation in Part B:

Moderately to severely active RA defined by the following:

Screening and Day 1:

1. 6 or more tender joints on the tender joint count based on 68 joints (TJC68), AND.

2. 6 or more swollen joints on the swollen joint count based on 66 joints (SJC66). Thedistal interphalangeal joints should be evaluated but not included in the totalcount to determine eligibility. Screening Only

3. Have a hsCRP ≥ ULN

• Inadequate response or intolerance to at least 1 but no more than 3 b/tsDMARDswith no more than 2 mechanisms of action. A lack of response is defined asdocumented continued or recurrent disease activity after at least 12 weeks oftreatment of RA. Intolerance is defined as any documented adverse effectassociated with a b/tsDMARD used according to its respective label.

Laboratory Assessments:

Cohort 3 Only:

• Anti-cyclic citrullinated peptide antibody (Anti-CCP) positive and/or rheumatoidfactor (RF) positive

Key Exclusion Criteria:

Medical Conditions; All Cohorts:

• Have a diagnosis of any generalized musculoskeletal disorder that would interferewith study procedures or assessments per the discretion of the investigator.

• History of opportunistic infection or immunodeficiency syndrome that would put theindividual at risk, as per investigator's judgment.

• Active infection that is clinically significant, per investigator's judgment, or anyinfection requiring hospitalization or treatment with intravenous anti-infectiveswithin 60 days of screening; or any infection requiring oral anti-infective therapywithin 30 days of screening.

• History of or current moderate to severe congestive heart failure (New York HeartAssociation class III or IV), or within the last 6 months prior to screening.

• History of lymphoproliferative disease or possible current lymphoproliferativedisease.

• History of organ or bone marrow transplant.

• Have a history of major surgery (requiring regional block or general anesthesia)within the last 12 weeks prior to screening or planned major surgery during thestudy.

• History of an infected joint prosthesis or other implanted device with theprosthesis or device still in situ.

• Clinically significant ECG abnormalities at screening, includingelectrocardiographic interval between the beginning of the Q wave and termination ofthe T wave, representing the time for both ventricular depolarization andrepolarization to occur (QT) interval corrected for heart rate using the Fridericiaformula (QTcF) > 450 msec, or hypokalemia if recurrent or persistent < 3.0 mmol/L,or family history of long QT syndrome

Prior/Concurrent Therapy or Clinical Study Experience:

• Administration of a live attenuated vaccine 4 weeks prior to Day 1 or plannedthroughout the study.

• Participation in any investigational drug/device clinical study within 4 weeks or 5half-lives prior to screening, whichever is longer. Exposure to investigationalbiologics should be discussed with the sponsor.

Diagnostic Assessments; All Cohorts:

• Any positive tuberculosis (TB) test using interferon-gamma release assay (IGRA)performed by central laboratory at screening. Tests with inconclusive results may berepeated one time. If an inconclusive test is repeated and is returned withinconclusive results a second time, the individual will be excluded from the study.Individuals with a history of latent or active TB who have been treated with a fullcourse of treatment, as per local guidelines, are eligible without the need for anIGRA at screening. Appropriate documentation of prior treatment is required.

• Evidence of active hepatitis C virus (HCV) infection. Individuals with positive HCVAb at screening require reflex testing for HCV ribonucleic acid (RNA). Individualswith positive HCV Ab but negative HCV RNA viral load are eligible per investigatorjudgment and require HCV viral load monitoring on Day 85 and Day 169.

• The results of the following laboratory tests performed at the central laboratory atscreening meet any of the criteria below (out-of-range laboratory values may berechecked 1 time, per investigator's judgment, before individual is considered ascreen failure):

1. Hemoglobin < 10.0 g/dL (SI: < 100 g/L)

2. White blood cells < 3.0 x 10^3 cells/mm^3 (SI: < 3.0 x 10^9 cells/L)

3. Neutrophils < 1.5 x 10^3 cells/mm^3 (SI: < 1.5 x 10^9 cells/L)

4. Lymphocytes < 1.0 x 10^3 cells/mm^3 (SI: < 1.0 x 10^9 cells/L)

5. Platelets < 100 x 10^3 cells/mm^3 (SI: < 100 x 10^9 cells/L)

6. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1.5 xupper limit of normal (ULN)

7. Total bilirubin level ≥ 2 x ULN unless the individual has been diagnosed withGilbert's disease and this is clearly documented

8. Creatinine clearance < 50 mL/min (SI: < 0.83 mL/s) based on the Cockcroft-Gaultformula

Note: Other protocol defined Inclusion/Exclusion criteria may apply