Trial Outcomes & Findings for A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate (NCT NCT01000610)

NCT ID: NCT01000610

Last Updated: 2017-08-16

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 18 participants
• Primary outcome timeframe: Days 1 and 15, every 8 weeks up to Week 24 and and then every 3 months up to 18 months for a total of 104 weeks
• Results posted on: 2017-08-16

Participant Flow

Participant milestones

Measure	Rituximab Participants received rituximab 1000 milligrams (mg) intravenous (iv) infusion on Days 1 and 15 along with methotrexate 10-25 mg weekly, orally or parenterally. Participants could receive concomitant treatment with corticosteroids (less than or equal to \[≤\] 10 milligrams per day (mg/day) prednisone or equivalent) or intra-articular corticosteroids, non-steroid anti-inflammatory drugs (NSAIDs) and analgesics throughout the study period at the discretion of the investigator. All participants received methylprednisolone100 mg iv prior to each rituximab infusion.
Overall Study STARTED	18
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Measure	Rituximab Participants received rituximab 1000 milligrams (mg) intravenous (iv) infusion on Days 1 and 15 along with methotrexate 10-25 mg weekly, orally or parenterally. Participants could receive concomitant treatment with corticosteroids (less than or equal to \[≤\] 10 milligrams per day (mg/day) prednisone or equivalent) or intra-articular corticosteroids, non-steroid anti-inflammatory drugs (NSAIDs) and analgesics throughout the study period at the discretion of the investigator. All participants received methylprednisolone100 mg iv prior to each rituximab infusion.
Overall Study Adverse Event	1
Overall Study Lost to Follow-up	4
Overall Study Treatment failure	1

Baseline Characteristics

A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate

Baseline characteristics by cohort

Measure	Rituximab n=18 Participants Participants received rituximab 1000 mg iv infusion on Days 1 and 15 along with methotrexate 10-25 mg weekly, orally or parenterally. Participants could receive concomitant treatment with corticosteroids (≤ 10 mg/day prednisone or equivalent) or intra-articular corticosteroids, NSAIDs and analgesics throughout the study period at the discretion of the investigator. All participants received methylprednisolone 100 mg iv prior to each rituximab infusion.
Age, Continuous	53.4 years STANDARD_DEVIATION 7.91 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Days 1 and 15, every 8 weeks up to Week 24 and and then every 3 months up to 18 months for a total of 104 weeks

Population: Safety Population: Included all participants who have received any part of an infusion of study medication.

Outcome measures

Measure	Rituximab n=18 Participants Participants received rituximab 1000 mg iv infusion on Days 1 and 15 along with methotrexate 10-25 mg weekly, orally or parenterally. Participants could receive concomitant treatment with corticosteroids (≤ 10 mg/day prednisone or equivalent) or intra-articular corticosteroids, NSAIDs and analgesics throughout the study period at the discretion of the investigator. All participants received methylprednisolone 100 mg iv prior to each rituximab infusion.
Number of Participants Reporting Adverse Events (AEs) Participants who experienced an AE	11 number of participants
Number of Participants Reporting Adverse Events (AEs) Participants who experienced more than 1 AE	7 number of participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT population; Only participants with DAS28 values at both Baseline and Week 24 were included in the analysis.

The DAS28 score is a measure of the participant's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], participant's global assessment of disease activity [visual analog scale: [VAS] 0 equals (=) no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to 10. Scores less than (<) 2.6 indicate best disease control and scores greater than or equal to (≥) 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6. The average improvement at each visit to the group score is equal to the formula (Previous DAS28 minus [-] current DAS 28)/ Previous DAS 28 x 100. Negative percentages indicate that the participant has worsened in comparison to last evaluation, and positive percentages indicate improvement of its DAS28 score and correlated with a bettering of clinical situation.

Outcome measures

Measure

Rituximab n=16 Participants Participants received rituximab 1000 mg iv infusion on Days 1 and 15 along with methotrexate 10-25 mg weekly, orally or parenterally. Participants could receive concomitant treatment with corticosteroids (≤ 10 mg/day prednisone or equivalent) or intra-articular corticosteroids, NSAIDs and analgesics throughout the study period at the discretion of the investigator. All participants received methylprednisolone 100 mg iv prior to each rituximab infusion.

Percentage Change in Disease Activity Score 28 (DAS28) From Baseline to Week 24

-1.7 percentage change from baseline Standard Deviation 49.4

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: ITT population; Only participants with DAS28 values at both Baseline and Week 24 were included in the analysis.

The DAS28 score is a measure of the participant's disease activity calculated using the TJC [28 joints], SJC [28 joints], participant's global assessment of disease activity [VAS: 0 = no disease activity to 100 = maximum disease activity] and the ESR for a total possible score of 0 to 10. Scores < 2.6 indicate best disease control and scores ≥ 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6. An improvement of >1.2 was considered to be clinically significant improvement.

Outcome measures

Measure

Rituximab n=16 Participants Participants received rituximab 1000 mg iv infusion on Days 1 and 15 along with methotrexate 10-25 mg weekly, orally or parenterally. Participants could receive concomitant treatment with corticosteroids (≤ 10 mg/day prednisone or equivalent) or intra-articular corticosteroids, NSAIDs and analgesics throughout the study period at the discretion of the investigator. All participants received methylprednisolone 100 mg iv prior to each rituximab infusion.

Percentage of Participants Whose DAS28 Improved by >1.2 at Week 24

75.0 percentage of participants

SECONDARY outcome

Timeframe: Screening and Week 84

Population: ITT population; only participants with an assessment at both screening and Week 84 were included in the analysis.

Bone mineral density test was performed using x-ray radiation and the values of bone density were provided directly by the apparatus as grams per square centimeter (g/cm^2) . T-score is the number of standard deviations above or below the mean for a healthy 30 year old adult of the same sex and ethnicity as the participant. A T-score with above -1 is normal bone density level. A T-score between -1 and -2.5 means that the bone density is below normal and it might be a sign of an osteopenia and may also lead into osteoporosis. A T-score below -2.5 indicates osteoporosis.

Outcome measures

Measure	Rituximab n=1 Participants Participants received rituximab 1000 mg iv infusion on Days 1 and 15 along with methotrexate 10-25 mg weekly, orally or parenterally. Participants could receive concomitant treatment with corticosteroids (≤ 10 mg/day prednisone or equivalent) or intra-articular corticosteroids, NSAIDs and analgesics throughout the study period at the discretion of the investigator. All participants received methylprednisolone 100 mg iv prior to each rituximab infusion.
Change in Bone Density (in Participants Untreated With Bisphosphonates) Screening	-1.82 t-score
Change in Bone Density (in Participants Untreated With Bisphosphonates) Week 84	-1.6 t-score

Adverse Events

Rituximab

Serious events: 6 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Rituximab n=18 participants at risk Participants received rituximab 1000 mg iv infusion on Days 1 and 15 along with methotrexate 10-25 mg weekly, orally or parenterally. Participants could receive concomitant treatment with corticosteroids (≤ 10 mg/day prednisone or equivalent) or intra-articular corticosteroids, NSAIDs and analgesics throughout the study period at the discretion of the investigator. All participants received methylprednisolone 100 mg iv prior to each rituximab infusion.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
Blood and lymphatic system disorders Persistent thrombopenia	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
Gastrointestinal disorders Rectal bleeding	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
Cardiac disorders Ventricular Extra systolebigeminy	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
Injury, poisoning and procedural complications Severe infusion reaction	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
Respiratory, thoracic and mediastinal disorders Dyspnea	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.

Other adverse events

Measure	Rituximab n=18 participants at risk Participants received rituximab 1000 mg iv infusion on Days 1 and 15 along with methotrexate 10-25 mg weekly, orally or parenterally. Participants could receive concomitant treatment with corticosteroids (≤ 10 mg/day prednisone or equivalent) or intra-articular corticosteroids, NSAIDs and analgesics throughout the study period at the discretion of the investigator. All participants received methylprednisolone 100 mg iv prior to each rituximab infusion.
Eye disorders Blurred Vision	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
Endocrine disorders Hyperglycemia	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
Infections and infestations Multi-sensitive Streptococcus Cystitis	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
Blood and lymphatic system disorders Hypertension	11.1% 2/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
Skin and subcutaneous tissue disorders Keratitis Secca	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
General disorders Red Throat	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
Ear and labyrinth disorders Vertigo	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
General disorders Somnolence	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
Infections and infestations Influenza	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
Musculoskeletal and connective tissue disorders Muscular Pain	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
General disorders Nocturnal Sweating	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
General disorders Headache	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
Respiratory, thoracic and mediastinal disorders Dyspnea Stage 2	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
Respiratory, thoracic and mediastinal disorders Productive Cough-Yellow Expectorations	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.
Infections and infestations Pneumopathy Infection	5.6% 1/18 • AEs were recorded from the day of first infusion until the End of Study at 104 weeks.

Additional Information

Medical Communications

Hoffmann- LaRoche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER