Phase 2
Completed N=578
Safety and Efficacy Study of GDC-0853 Compared With Placebo and Adalimumab in Participants With Rheumatoid Arthritis (RA)
Source: ClinicalTrials.gov NCT02833350 ↗Enrolled (actual)
578
Serious AEs
1.2%
Results posted
Sep 2019
Primary outcomePrimary: Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 1) — 17.5; 27.5; 34.5; 14.5 Percentage — p=0.2503
Summary
This is a multicenter, Phase II, randomized, double-blind, placebo-controlled, active comparator (Cohort 1 only), parallel-group, dose-ranging study to evaluate the efficacy and safety of GDC-0853 in participants with moderate to severe active RA and an inadequate response to previous methotrexate (MTX) therapy (Cohort 1) or MTX and tumor necrosis factor (TNF) therapy who may have also had exposure to no more than one non-TNF inhibitor biologic (Cohort 2).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 1) |
17.5; 27.5; 34.5; 14.5; 36.0 | 0.2503 |
| PRIMARY Percentage of Participants With Adverse Events |
37.5; 42.2; 50.9; 45.5; 45.0; 22.4 | — |
| SECONDARY Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Adalimumab (Cohort 1) |
17.5; 27.5; 34.5; 14.5; 36.0 | 0.1694 |
| SECONDARY Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 2) |
25.0; 12.0 | 0.0717 |
| SECONDARY Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response |
10.0; 14.7; 13.6; 10.0; 25.2; 22.9 | — |
| SECONDARY Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response |
2.5; 2.8; 3.6; 2.7; 4.5; 6.3 | — |
| SECONDARY Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response |
0.0; 0.9; 0.9; 0.0; 0.0; 0.0 | — |
| SECONDARY Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) |
-0.34; -0.35; -0.37; -0.33; -0.92; -0.49 | 0.8504 |
| SECONDARY Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP]) |
-0.43; -0.48; -0.49; -0.37; -1.10; -0.63 | 0.5807 |
| SECONDARY Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR]) |
-0.35; -0.42; -0.39; -0.34; -0.72; -0.50 | 0.9193 |
| SECONDARY Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) |
-0.45; -0.54; -0.52; -0.37; -0.93; -0.65 | 0.6083 |
| SECONDARY Percentage of Participants With DAS Low Disease Activity |
0.0; 0.9; 1.8; 0.0; 1.8; 2.1 | 1.0000 |
| SECONDARY Percentage of Participants With DAS Remission |
0.0; 0.0; 0.0; 0.0; 0.0; 2.1 | 1.0000 |
| SECONDARY Percentage of Participants Meeting the Boolean-based Remission Criteria |
0.0; 0.9; 0.0; 0.0; 0.0; 0.0 | 1.0000 |
| SECONDARY Change From Baseline in Clinical Disease Activity Index (CDAI) |
-5.45; -6.70; -7.40; -4.71; -9.64; -8.61 | 0.4960 |
| SECONDARY Percentage of Participants Meeting the CDAI-based Remission Criteria |
0.0; 0.9; 0.9; 0.0; 0.0; 0.0 | 1.0000 |
| SECONDARY Change From Baseline in Simplified Disease Activity Index (SDAI) |
-5.36; -6.48; -6.99; -4.75; -10.86; -8.73 | 0.5455 |
| SECONDARY Percentage of Participants Meeting the SDAI-based Remission Criteria |
0.00; 0.9; 0.00; 0.00; 0.00; 0.00 | 1.0000 |
| SECONDARY Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components |
5.57; 5.71; 6.59; 3.54; 6.41; 5.35 | — |
| SECONDARY Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score |
9.00; 8.21; 8.95; 7.08; 9.59; 8.85 | — |
| SECONDARY Change From Baseline in Tender/Painful Joint Count (68 Joint Count) |
-2.79; -4.12; -3.33; -3.81; -5.58; -6.57 | — |
| SECONDARY Change From Baseline in Swollen Joint Count (66 Joint Count) |
-1.84; -2.89; -3.45; -3.35; -3.94; -3.45 | — |
| SECONDARY Change From Baseline in Patient Assessment Score of Arthritis Pain |
-9.00; -9.20; -11.18; -4.12; -15.75; -11.94 | — |
| SECONDARY Change From Baseline in Patient Global Assessment Score of Arthritis Pain |
-9.00; -10.30; -11.82; -3.07; -18.33; -13.15 | — |
| SECONDARY Change From Baseline in Physician's Global Assessment Score of Arthritis |
-7.89; -10.68; -12.82; -5.85; -14.23; -9.57 | — |
| SECONDARY Change From Baseline in C-Reactive Protein (CRP) Levels |
0.14; 0.30; 0.22; 0.01; -1.21; -0.12 | — |
| SECONDARY Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score |
-0.20; -0.15; -0.22; -0.10; -0.26; -0.19 | — |
| SECONDARY Area Under the Concentration Time Curve From Time 0 to Time 24 of GDC-0853 at Steady State (AUC0-24,ss) |
1170; 2910; 9380; 9890 | — |
| SECONDARY Maximum Observed Plasma Concentration of GDC-0853 at Steady State (Cmax,ss) |
110; 280; 591; 621 | — |
| SECONDARY Minimum Observed Plasma Concentration of GDC-0853 at Steady State (Cmin,ss) |
22.4; 54.7; 250; 263 | — |
Eligibility Criteria
Inclusion Criteria
- Have a diagnosis of adult-onset RA as defined by the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for RA
- RA disease activity by joint counts and laboratory markers of inflammation: greater than or equal to (>=) 6 tender/painful joints on motion (68 joint count) and >= 6 swollen joints (66 joint count) at both screening and Day 1 (randomization)
- For MTX-inadequate response (IR) participants: must have had an inadequate response to MTX
- For TNF-IR participants: must have had an inadequate response or intolerance to previous treatment with at least 1 and no more than 2 biologic TNF-alpha inhibitors and may have also been exposed to no more than one biologic non-TNF-alpha inhibitor
- High sensitivity C-reactive protein of >= 0.400 milligrams per deciliter (mg/dL) for Cohort 1 and >= 0.650 mg/dL for Cohort 2 at screening
Exclusion Criteria
- History of or current inflammatory joint disease other than RA or other systemic autoimmune disorder
- For MTX-IR participants: History of treatment with any TNF inhibitor, including biosimilar equivalents and history of treatment with biologic non-TNF-alpha inhibitor for RA
- For all participants: Previous treatment with cell-depleting therapy including B cell-depleting therapy (e.g., anti-cluster of differentiation 20-directed therapy such as rituximab), tofacitinib, or other Janus kinase inhibitor(s), or alkylating agents
- Current treatment with medications that are well known to prolong the QT interval at doses that have a clinically meaningful effect on QT
- History of non-gallstone-related pancreatitis or chronic pancreatitis
- Evidence of serious uncontrolled concomitant cardiac, neurologic, pulmonary, renal, hepatic, endocrine, metabolic, or gastrointestinal disease
- Evidence of chronic and/or active hepatitis B or C
- Women who are pregnant, nursing (breast feeding), or intending to become pregnant during the study or within 60 days after completion of the study
Data sourced from ClinicalTrials.gov (NCT02833350). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.