A Study to Evaluate Ocrelizumab Compared With Placebo in Patients With Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Therapy

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• Arthritis 3,554
• Arthritis, Rheumatoid 2,888

Keywords

• RA

Arthritis

3,554 studies on the registry are indexed under Arthritis; 317 are open to participants now.

This study's enrollment of 314 is above the median of 90 across 2,377 interventional studies indexed under Arthritis.

Lead sponsor

Genentech, Inc. is the lead sponsor of 507 studies on the registry; 23 are open to participants now.

Of its 90 completed or terminated interventional studies of FDA-regulated products, 50 (56%) have results posted.

Study arms

• Placebo comparator
  Placebo

  Participants received matching placebo: * on Day 15 of Cycle 1 (Participants who were administered OCR 400 mg on Day 1 of a Cycle 1 in combination with Methotrexate) * on both Days 1 and Day 15 of Cycle 1 (Participants who were randomized to the Placebo + Methotrexate group)

  Drug: Methotrexate · Drug: Placebo

• Experimental
  Ocrelizumab 400mg

  Participants received Ocrelizumab 400mg in combination with Methotrexate on Day 1, Cycle 1.

  Drug: Methotrexate · Drug: Ocrelizumab

• Experimental
  Ocrelizumab 200mg

  Participants received Ocrelizumab 200 mg in combination with Methotrexate on Day 1 and Day 15, Cycle 1.

  Drug: Methotrexate · Drug: Ocrelizumab

• Experimental
  Ocrelizumab 200mg/ Ocrelizumab 200mg

  Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2

  Drug: Methotrexate · Drug: Ocrelizumab

• Experimental
  Ocrelizumab 200mg/ Ocrelizumab 400mg

  Participants who received two 200 mg infusions of Ocrelizumab + Methotraxate during Cycle 1 were re-randomized (1:1 randomization ratio) to receive a single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2

  Drug: Methotrexate · Drug: Ocrelizumab

• Experimental
  Ocrelizumab 400mg/ Ocrelizumab 400mg

  Participants who received single 400mg infusions of Ocrelizumab + Methotraxate during Cycle 1 received a infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2

  Drug: Methotrexate · Drug: Ocrelizumab

• Experimental
  Placebo/ Ocrelizumab 200mg

  Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive two infusions of 200 mg Ocrelizumab + Methotraxate during Cycle 2

  Drug: Methotrexate · Drug: Ocrelizumab · Drug: Placebo

• Experimental
  Placebo/ Ocrelizumab 400mg

  Participants who received placebo during Cycle 1 were re-randomized (1:1 randomization ratio) to receive single infusion of 400 mg Ocrelizumab + Methotraxate during Cycle 2

  Drug: Methotrexate · Drug: Ocrelizumab · Drug: Placebo

Interventions

• DrugMethotrexate

  Oral or parenteral repeating dose

• DrugOcrelizumab

  Ocrelizumab was administered as a slow intravenous (iv) infusion during each course as either 200 mg on Day 1 and Day 15 (OCR 200×2) or as 400 mg given on Day 1 (OCR 400×1). Ocrelizumab was administered in combination with Methotrexate.

• DrugPlacebo

  Intravenous repeating dose

Primary outcomes

1. Percentage of Participants With American College of Rheumatology (ACR) 20 Response

   ACR20 response: greater than or equal to (≥) 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (visual analog scale \[VAS\]), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) erythrocyte sedimentation rate (ESR) at each visit.

   Time frame: Week 24

Secondary outcomes

1. Percentage of Participants Achieving Disease Activity Score 28 (DAS28) Remission (DAS28 < 2.6)

   The DAS28 was derived from assessments of erythrocyte sedimentation rate (ESR) measured in millimeters per hour (mm/h), tender joint count on 28 joints (TJC28), swollen joint count on 28 joints (SJC28), and Patient's Global Assessment of disease activity according to 100--millimeter (mm) Visual Analog Scale (VAS). DAS28 score was calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. DAS28 score could range from 0 to 10, where higher score represented higher disease activity. The change from Week 24 to Week 40 was averaged among all participants, where negative changes indicated an improvement in disease activity.

   Time frame: Week 24

2. Change in DAS28 From Baseline

   The DAS28 was derived from assessments of erythrocyte sedimentation rate (ESR) measured in millimeters per hour (mm/h), tender joint count on 28 joints (TJC28), swollen joint count on 28 joints (SJC28), and Patient's Global Assessment of disease activity according to 100--millimeter (mm) Visual Analog Scale (VAS). DAS28 score was calculated as \[0.56 × square root of TJC\] + \[0.28 × square root of SJC\] + \[0.70 × natural log (ESR)\] + \[0.014 × VAS\]. DAS28 score could range from 0 to 10, where higher score represented higher disease activity. The change from Week 24 to Week 40 was averaged among all participants, where negative changes indicated an improvement in disease activity. The change is the difference in adjusted mean change from baseline in DAS28 between ocrelizumab 400 x 1 and ocrelizumab 200 x 2 with placebo.

   Time frame: Week 24

3. European League Against Rheumatism (EULAR) Response Rates (Categorical DAS Responders)

   Time frame: Week 24

4. Percentage of Participants Achieving an ACR50 Response

   The ACR50 response at any time was defined as \>/=50% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 50% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/dL).

   Time frame: Week 24

5. Percentage of Participants Achieving an ACR70 Response

   The ACR70 response at any time was defined as \>/=70% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 70% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/dL).

   Time frame: Week 24

6. Change From Baseline in the Individual Parameters of the ACR Core Set

   Change in the scores of the following parameters of ACR core set relative to respective baseline scores was measured: SJC (28 and 66 joints) and TJC (28 and 66 joints), patient's global assessment and physician's global assessment based on disease activity (both are expressed by VAS \[0 = no disease activity to 100 = maximum disease activity\]), HAQ (based on HAQ disability index \[HAQDI\]) which included 8 domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities) rated on a 4-point scale (0=without any difficulty to 3=unable to do), where the sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst), pain assessment using a VAS ranging from score 0 (no pain) to 100 (unbearable pain).

   Time frame: Week 24

7. Change From Baseline in the Individual Parameters of the ACR Core Set: C-Reactive Protein (CRP) Concentration

   Time frame: Week 24

8. Change From Baseline in the Individual Parameters of the ACR Core Set: Erythrocyte Sedimentation Rate (ESR)

   Time frame: Week 24

9. Percentage of Participants With a Reduction of Greater Than or Equal to 0.25 Units in the HAQ-DI Score

   Time frame: Week 24

10. Change in SF-36 Subscale and Summary Scores From Baseline

    Improved, change \> 5.42; Unchanged, -5.42 \<= Change \<= 5.42; Worsened, change \< -5.42

    Time frame: Week 24

11. Change in FACIT-F Fatigue Assessment From Baseline

    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participants fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). Clinically relevant improvement is defined as a greater than or equal to (≥)5-point change from Baseline.

    Time frame: Baseline, Weeks 4, 12, and 24

12. Percentage of Participants Achieving an ACR20 Response

    ACR20 response: greater than or equal to (≥) 20% improvement in tender or swollen joint counts and 20% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) participant assessment of disease activity, 3) Patient Assessment of Pain (visual analog scale \[VAS\]), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) erythrocyte sedimentation rate (ESR) at each visit.

    Time frame: Week 48

13. Percentage of Participants Achieving an ACR50 Response

    The ACR50 response at any time was defined as \>/=50% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 50% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/dL).

    Time frame: Week 48

14. Percentage of Participants Achieving an ACR70 Response

    The ACR70 response at any time was defined as \>/=70% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 70% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) Patient's global assessment of disease activity according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/dL).

    Time frame: Week 48

15. Percentage of Participants Achieving DAS28 Remission (DAS28 < 2.6)

    Time frame: Week 48

16. Cmax: Maximum Observed Serum Concentration of Ocrelizumab Following First Infusion

    Time frame: Week 24, 48

17. Csecond: Maximum Observed Serum Concentration of Ocrelizumab Following Second Infusion

    Time frame: Day 15 of Cycles 1 and 2

Baseline characteristics

Publications

• Emery P, Rigby W, Tak PP, Dorner T, Olech E, Martin C, Millar L, Travers H, Fisheleva E. Safety with ocrelizumab in rheumatoid arthritis: results from the ocrelizumab phase III program. PLoS One. 2014 Feb 3;9(2):e87379. doi: 10.1371/journal.pone.0087379. eCollection 2014. PubMed 24498318 ↗

Individual participant data

Plan to share: Yes — Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).