Rheumatoid Arthritis
Conditions
Brief summary
The goals of this clinical study are to learn more about the study drug, GS-0272, and its safety and tolerability following multiple doses in participants with rheumatoid arthritis (RA). The primary objectives of this study are to assess the safety and tolerability of multiple ascending doses of GS-0272 and to characterize the pharmacokinetics of GS-0272 following multiple doses of GS-0272, in participants with RA.
Interventions
DRUGGS-0272
Administered subcutaneously (for Part A) Administered intravenously or subcutaneously (for Part B)
DRUGPlacebo
Administered subcutaneously (for Part A) Administered intravenously or subcutaneously (for Part B)
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Age limit for the Republic of Korea for male or nonpregnant female is between 19 and 75 years of age. Part A (Rheumatoid Arthritis (RA) Cohorts)-Specific Inclusion Criteria: * Diagnosis of RA at least 3 months prior to screening fulfilling the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria. * Ongoing treatment with 1 or 2 conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for at least 12 weeks prior to the first dose of study drug, with a stable dose for at least 4 weeks prior to the first dose of study drug, as follows: * Individuals must not be on a biologic disease-modifying antirheumatic drugs (bDMARD)/targeted synthetic disease-modifying antirheumatic drug (tsDMARD) at Day 1 or during the study and must discontinue b/tsDMARD use for at least 4 weeks (with the exception of rituximab, which must be discontinued for at least 16 weeks) prior to the first dose of study drug. Part B (Active RA Cohort)-Specific Inclusion Criteria: * Participant is seropositive as demonstrated by a positive anti-cyclic citrullinated peptide (anti-CCP) antibody and/or positive rheumatoid factor at screening. * Participant has an elevated high-sensitivity C-reactive protein (hsCRP) greater than upper limit of normal (ULN). * Participant has 6 or more swollen and 6 or more tender joints as assessed on the SJC66/TJC68. Distal interphalangeal joints will not be counted towards the 6 joint eligibility. * Participant has had inadequate response or intolerance to at least 1 but not more than 3 bDMARD/tsDMARD therapeutics with no more than 2 MOAs. A lack of response is defined as documented continued or recurrent disease activity after at least 12 weeks of treatment of RA. Key
Exclusion criteria
* Meet any of the protocol-specified infection criteria (hepatitis C, Hepatitis B, HIV, tuberculosis, others). * Inadequate response or intolerance to more than 3 bDMARDs/tsDMARDs with more than 2 MOAs. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing Adverse Events (AEs) | First dose up to Week 12 plus 70 days | — |
| Percentage of Participants Experiencing Serious Adverse Events (SAEs) | First dose up to Week 12 plus 70 days | — |
| Percentage of Participants With Laboratory Abnormalities | First dose up to Week 12 plus 70 days | — |
| Pharmacokinetics (PK) of GS-0272: AUCtau | Day 1 predose through Day 197 | AUCtau is defined as the area under the concentration versus time curve over the dosing interval. |
| PK of GS-0272: Cmax | Day 1 predose through Day 197 | Cmax is defined the maximum observed plasma drug concentration. |
| PK of GS-0272: Tmax | Day 1 predose through Day 197 | Tmax is defined as the time to maximum observed concentration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of Antidrug Antibodies (ADAs) for GS-0272 | Baseline (Day 1) through Day 197 | Prevalence of ADAs will be measured as the proportion of participants who had at least one positive ADA sample (baseline or post-baseline) among all participants evaluable for ADA prevalence. |
| Incidence of ADAs for GS-0272 | Baseline (Day 1) through Day 197 | ADA incidence will be measured as the proportion of participants who have treatment-emergent ADA sample (post-baseline) among all participants evaluable for ADA incidence. |
| Part B: Change from Baseline in Disease Activity Score 28 (DAS28) C-Reactive Protein (CRP) in Participants with Moderate-to-Severe RA | Baseline, Week 12 | Disease Activity Score 28 C-Reactive Protein (DAS28 (CRP)) is a measure of the participant's disease activity calculated using the tender joint counts (28 joints), swollen joint counts (28 joints), participant's global assessment of disease activity (visual analog scale: 0 = no disease activity to 100 = maximum disease activity) and CRP for a total possible score of 1 to 9.4. Higher values indicate higher disease activity. |
Countries
Georgia, Moldova, South Korea, United Kingdom, United States
Contacts
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Outcome results
None listed