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Safety and Efficacy Study of GDC-0853 Compared With Placebo and Adalimumab in Participants With Rheumatoid Arthritis (RA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02833350
Recruitment Status : Completed
First Posted : July 14, 2016
Last Update Posted : October 19, 2018
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Brief 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).

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: GDC-0853 Drug: Adalimumab Drug: Folic Acid Drug: MTX Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 578 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Two-Cohort Randomized Phase II, Double-Blind, Parallel Group Study in Patients With Active Rheumatoid Arthritis Evaluating the Efficacy and Safety of GDC-0853 Compared With Placebo and Adalimumab in Patients With an Inadequate Response to Previous Methotrexate Therapy (Cohort 1) and Compared With Placebo in Patients With an Inadequate Response or Intolerance to Previous TNF Therapy (Cohort 2)
Actual Study Start Date : September 9, 2016
Actual Primary Completion Date : July 2, 2018
Actual Study Completion Date : July 2, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Adalimumab

Arm Intervention/treatment
Experimental: Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
Participants of Cohort 1 will receive GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Drug: GDC-0853
Participants will receive GDC-0853 at low, mid, or high doses, orally once or twice daily for 12 weeks in Cohort 1 or 2.
Other Name: RO7010939

Drug: Folic Acid
Participants will receive stable background therapy of folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

Drug: MTX
Participants will receive stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines).

Drug: Placebo
Participants will receive placebo matched to adalimumab, subcutaneously Q2W and/or placebo matched to GDC-0853, orally once or twice daily for 12 weeks in Cohort 1 or 2.

Experimental: Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
Participants of Cohort 1 will receive GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Drug: GDC-0853
Participants will receive GDC-0853 at low, mid, or high doses, orally once or twice daily for 12 weeks in Cohort 1 or 2.
Other Name: RO7010939

Drug: Folic Acid
Participants will receive stable background therapy of folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

Drug: MTX
Participants will receive stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines).

Drug: Placebo
Participants will receive placebo matched to adalimumab, subcutaneously Q2W and/or placebo matched to GDC-0853, orally once or twice daily for 12 weeks in Cohort 1 or 2.

Experimental: Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
Participants of Cohort 1 will receive GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Drug: GDC-0853
Participants will receive GDC-0853 at low, mid, or high doses, orally once or twice daily for 12 weeks in Cohort 1 or 2.
Other Name: RO7010939

Drug: Folic Acid
Participants will receive stable background therapy of folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

Drug: MTX
Participants will receive stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines).

Drug: Placebo
Participants will receive placebo matched to adalimumab, subcutaneously Q2W and/or placebo matched to GDC-0853, orally once or twice daily for 12 weeks in Cohort 1 or 2.

Active Comparator: Cohort 1: GDC-0853 Placebo + Adalimumab
Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Drug: Adalimumab
Participants will receive adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks.

Drug: Folic Acid
Participants will receive stable background therapy of folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

Drug: MTX
Participants will receive stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines).

Drug: Placebo
Participants will receive placebo matched to adalimumab, subcutaneously Q2W and/or placebo matched to GDC-0853, orally once or twice daily for 12 weeks in Cohort 1 or 2.

Placebo Comparator: Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Drug: Folic Acid
Participants will receive stable background therapy of folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

Drug: MTX
Participants will receive stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines).

Drug: Placebo
Participants will receive placebo matched to adalimumab, subcutaneously Q2W and/or placebo matched to GDC-0853, orally once or twice daily for 12 weeks in Cohort 1 or 2.

Experimental: Cohort 2: GDC-0853 High Dose
Participants of Cohort 2 will receive GDC-0853 high dose, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Drug: GDC-0853
Participants will receive GDC-0853 at low, mid, or high doses, orally once or twice daily for 12 weeks in Cohort 1 or 2.
Other Name: RO7010939

Drug: Folic Acid
Participants will receive stable background therapy of folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

Drug: MTX
Participants will receive stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines).

Placebo Comparator: Cohort 2: GDC-0853 Placebo
Participants of Cohort 2 will receive placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Drug: Folic Acid
Participants will receive stable background therapy of folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

Drug: MTX
Participants will receive stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines).

Drug: Placebo
Participants will receive placebo matched to adalimumab, subcutaneously Q2W and/or placebo matched to GDC-0853, orally once or twice daily for 12 weeks in Cohort 1 or 2.




Primary Outcome Measures :
  1. Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 1) [ Time Frame: Day 84 ]
  2. Percentage of Participants With Adverse Events [ Time Frame: Day 1 up to 8 weeks after last dose (up to Week 20) ]

Secondary Outcome Measures :
  1. Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Adalimumab (Cohort 1) [ Time Frame: Day 84 ]
  2. Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 2) [ Time Frame: Day 84 ]
  3. Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response [ Time Frame: Days 7, 14, 28, 56, and 84 ]
  4. Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response [ Time Frame: Days 7, 14, 28, 56, and 84 ]
  5. Percentage of Participants Experiencing High Disease Activity to Clinical Remission Using the Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) [ Time Frame: Days 7, 14, 28, 56, and 84 ]
  6. Percentage of Participants Experiencing High Disease Activity to Clinical Remission Using the Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP]) [ Time Frame: Days 7, 14, 28, 56, and 84 ]
  7. Percentage of Participants Experiencing High Disease Activity to Clinical Remission Using the Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR]) [ Time Frame: Days 7, 14, 28, 56, and 84 ]
  8. Percentage of Participants Experiencing High Disease Activity to Clinical Remission Using the Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) [ Time Frame: Days 7, 14, 28, 56, and 84 ]
  9. Percentage of Participants Achieving ACR50 Response [ Time Frame: Days 7, 14, 28, and 56 ]
  10. Percentage of Participants with Response as Assessed by Tender/Painful Joint Count (68 Joint Count) [ Time Frame: Days 7, 14, 28, 56, and 84 ]
  11. Percentage of Participants with Response as Assessed by Swollen Joint Count (66 Joint Count) [ Time Frame: Days 7, 14, 28, 56, and 84 ]
  12. Percentage of Participants with Response as Assessed by Patient Assessment Score of Arthritis Pain [ Time Frame: Days 7, 14, 28, 56, and 84 ]
  13. Percentage of Participants with Response as Assessed by Patient Global Assessment Score of Arthritis Pain [ Time Frame: Days 7, 14, 28, 56, and 84 ]
  14. Percentage of Participants with Response as Assessed by Physician's Global Assessment Score of Arthritis [ Time Frame: Days 7, 14, 28, 56, and 84 ]
  15. Percentage of Participants with Response as Assessed by C-Reactive Protein (CRP) Levels [ Time Frame: Days 7, 14, 28, 56, and 84 ]
  16. Percentage of Participants with Response as Assessed by Health Assessment Questionnaire-Disability Index (HAQ-DI) Score [ Time Frame: Days 7, 14, 28, 56, and 84 ]
  17. Percentage of Participants Meeting the Boolean-based Remission Criteria [ Time Frame: Days 7, 14, 28, 56, and 84 ]
  18. Percentage of Participants Meeting the Simplified Disease Activity Index (SDAI)-based Remission Criteria [ Time Frame: Days 7, 14, 28, 56, and 84 ]
  19. Percentage of Participants Meeting the Clinical Disease Activity Index (CDAI)-based Remission Criteria [ Time Frame: Days 7, 14, 28, 56, and 84 ]
  20. 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Score [ Time Frame: Day 84 ]
  21. Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score [ Time Frame: Day 84 ]
  22. Area Under the Concentration Time Curve From Time 0 to Time t of GDC-0853 at Steady State (AUC0-t,ss) [ Time Frame: Pre-dose (0 hours) on Days 28, 56, and 84 and up to 10 hours post-dose on Day 28 ]
  23. Maximum Observed Plasma Concentration of GDC-0853 at Steady State (Cmax,ss) [ Time Frame: Pre-dose (0 hours) on Days 28, 56, and 84 and up to 10 hours post-dose on Day 28 ]
  24. Time to Reach Maximum Observed Plasma Concentration of GDC-0853 at Steady State (Tmax,ss) [ Time Frame: Pre-dose (0 hours) on Days 28, 56, and 84 and up to 10 hours post-dose on Day 28 ]
  25. Minimum Observed Plasma Concentration of GDC-0853 at Steady State (Ctrough,ss) [ Time Frame: Pre-dose (0 hours) on Days 28, 56, and 84 ]
  26. Plasma Decay Half-Life of GDC-0853 at Steady State (t1/2,ss) [ Time Frame: Pre-dose (0 hours) on Days 28, 56, and 84 and up to 10 hours post-dose on Day 28 ]
  27. Apparent Oral Clearance of GDC-0853 at Steady State (CL/F,ss) [ Time Frame: Pre-dose (0 hours) on Days 28, 56, and 84 and up to 10 hours post-dose on Day 28 ]
  28. Change from Baseline in SDAI at Days 7, 14, 28, 56 and 84 [ Time Frame: Baseline, Days 7, 14, 28, 56 and 84 ]
  29. Change from Baseline in CDAI at Days 7, 14, 28, 56 and 84 [ Time Frame: Baseline, Days 7, 14, 28, 56 and 84 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02833350


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Sponsors and Collaborators
Genentech, Inc.
Investigators
Layout table for investigator information
Study Director: Clinical Trials Hoffmann-La Roche

Layout table for additonal information
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT02833350     History of Changes
Other Study ID Numbers: GA29350
2016-000335-40 ( EudraCT Number )
First Posted: July 14, 2016    Key Record Dates
Last Update Posted: October 19, 2018
Last Verified: October 2018

Additional relevant MeSH terms:
Layout table for MeSH terms
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adalimumab
Folic Acid
Vitamin B Complex
Anti-Inflammatory Agents
Antirheumatic Agents
Hematinics
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs