A Phase III Transition Study of DRL Rituximab to Reference Medicinal Products

NCT04268771 | Completed Phase 3 Results FDA Drug

• 1 other identifier: RI-01-007
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 26

Brief Summary

The objective of the current study is to assess the immunogenicity and safety of transitioning subjects with RA to DRL\_RI from US-rituximab/EU-rituximab to continued treatment with US-rituximab/EU-rituximab. The primary objective of this study is to assess the immunogenicity of transitioning subjects with RA to DRL\_RI (biosimilar rituximab) from US-rituximab/EU-rituximab to continued treatment with US-rituximab/EU-rituximab To assess the safety of transitioning subjects with RA to DRL\_RI from US-rituximab/EU-rituximab to continued treatment with US-rituximab/EU-rituximab.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (5)

• Number of Subjects With Positive Anti-Drug Antibodies (ADA) on Day 1

  For Immunogenicity: Number of subjects with positive Anti-Drug Antibodies (ADA) on Day 1 was reported

  ADA will be obtained before the administration of study treatment on Day 1

• Number of Subjects With Positive Anti-Drug Antibodies (ADA) on Day 15

  For Immunogenicity: Number of subjects with positive Anti-Drug Antibodies (ADA) on Day 15 was reported

  ADA will be obtained before the administration of study treatment on Day 15

• Number of Subjects With Positive Anti-Drug Antibodies (ADA) at Week 4

  For Immunogenicity: Number of subjects with positive Anti-Drug Antibodies (ADA) at Week 4 was reported

  ADA will be obtained before the administration of study treatment at Week 4

• Number of Subjects With Positive Anti-Drug Antibodies (ADA) at Week 8

  For Immunogenicity: Number of subjects with positive Anti-Drug Antibodies (ADA) at Week 8 was reported

  ADA will be obtained before the administration of study treatment at Week 8

• Number of Subjects With Positive Anti-Drug Antibodies (ADA) at Week 12 Visits

  For Immunogenicity: Number of subjects with positive Anti-Drug Antibodies (ADA) at Week 12 visits was reported

  ADA will be obtained at Week 12

Secondary Outcomes (8)

• Number of Subjects Reporting Anaphylactic Reactions at Dosing Time Points (Either at Week 1 or Week 3)

  Assessments of Anaphylactic reactions will be carried out at either Week 1 or Week 3

• Number of Subjects Reporting TEAEs (Treatment Emergent Adverse Events) That Led to Study Drug Discontinuation at Either Week 1 or Week 3 Dosing Timepoint

  Assessment of AE's (Adverse Events) that led to study drug discontinuation were carried out at either week 1 or week 3 dosing timepoint

• Number of Subjects Reporting SAEs (Serious Adverse Events) From Baseline (Week 1) to End of Study (Week 26)

  Assessment of SAE's was carried out from baseline (week 1) to end of study (week 26)

• Number of TEAEs Reported From Baseline (Week 1) to End of Study (Week 26)

  Assessment of AE's will be carried out from baseline (week 1) to end of study (week 26)

• Number of Subjects Reporting AE From Baseline (Week 1) to End of Study (Week 26)

  Assessment of AE's will be carried out from baseline (week 1) to end of study (week 26)

Study Arms (2)

Arm A: DRL_RI

EXPERIMENTAL

Subjects who have already received at least 1 full course comprising two 1000 mg infusions of either US-rituximab or EU-rituximab and are candidates for re-treatment with Rituximab, will be enrolled. DRL\_RI will be administrated in combination with MTX as two 1000 mg infusions on Day 1 and Day 15

Biological: Experimental: Arm A: DRL_RI

Arm B: US-Rituximab or EU-Rituximab

ACTIVE COMPARATOR

Subjects who have already received at least 1 full course comprising two 1000 mg infusions of either US-rituximab or EU-rituximab and are candidates for re-treatment with rituximab, will be enrolled. Patients enrolled in Arm -B will continue to receive US-rituximab or EU-rituximab. The rituximab reference product used (US-licensed rituximab \[Rituxan\] or EU-approved rituximab \[MabThera\]) should be the same in the prior and the randomized treatment course, respectively.

Biological: Arm B: Rituxan®/Mabthera®

Interventions

Experimental: Arm A: DRL_RI BIOLOGICAL

Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion

Arm A: DRL_RI

Arm B: Rituxan®/Mabthera® BIOLOGICAL

Reference product US- rituximab (Rituxan®) or EU-rituximab (MabThera®), 100mg or 500mg, concentrate for solution for infusion

Arm B: US-Rituximab or EU-Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects aged 18 years or older who have provided valid written informed consent.
• Subjects with a diagnosis of active RA who are eligible for the subsequent treatment course with US-rituximab or EU-rituximab according to the clinical judgment of the investigator.
• Documented evidence that subject has received at least 1 full course comprising two 1000 mg infusions of either US-rituximab at least 16 weeks prior to the randomization visit or EU-rituximab at least 24 weeks prior to the day of randomization visit.
• Subjects receiving a stable dose of weekly methotrexate (MTX) for at least 4 weeks prior to randomization (between 7.5 mg and 25 mg) and folic acid (at least 5 mg per week.

You may not qualify if:

• Subjects with RA in functional Class IV
• Subjects with human immunodeficiency virus (positive HIV1Ab or HIV2Ab), hepatitis B virus and/or hepatitis C virus infection, including those with positive results in the viral disease screening.
• Subjects with active tuberculosis. Subjects with evidence of latent TB or a history of TB must have completed treatment or have initiated treatment for at least 1 month before the first dose of study treatment (Day 1). TB testing is required only if it is required by local regulations or practice.
• Active systemic infection.
• Severely immunocompromised.
• History of severe hypersensitivity to either US-rituximab or EU-rituximab or any of its excipients requiring drug discontinuation.
• Any serious illness or uncontrolled medical condition, including but not limited to severe infections, significant hepatic or renal disease, uncontrolled hypertension despite treatment (defined as blood pressure ≥160/95 mmHg), congestive heart failure (New York Heart Association \[NYHA\] Class III or IV), or other severe, uncontrolled cardiac disease or uncontrolled diabetes with immediate risk of acute complications.
• Any condition that in the opinion of the investigator represents an obstacle for study conduct and/or represents a potential unacceptable risk for subjects.
• Requires treatment with any biological medicinal product during the study other than the study treatment.
• Previous treatment with B-cell modulating or cell depleting biologic therapy except US-rituximab or EU-rituximab.
• Prior participation in this clinical trial or prior participation in any clinical trial with any monoclonal antibody within 12 months of screening or prior participation in any clinical trial within 3 months of screening or within 5 half-lives of the investigational drug or until the expected PD effect has returned to baseline, whichever is longer.
• Treatment with other biologic disease-modifying anti-rheumatic drugs, or Janus kinase (JAK) inhibitors administered within 12 weeks before the first dose of rituximab of the prior treatment course onwards till the date of randomization.
• Subjects with the following laboratory abnormalities:
• Subjects with screening total white blood cell count \<3000/μL, platelets \<100,000/μL, neutrophils \<1,500/μL, or hemoglobin \<8.5 g/dL
• Abnormal liver function tests such as aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase \>2 × upper limit of normal (ULN). A single parameter \>2 × ULN can be re-checked as soon as possible, at least prior to randomization, if required as per the investigator's discretion.

Sponsors & Collaborators

• Dr. Reddy's Laboratories Limited: lead
• PPD Development, LP: collaborator

Study Sites (26)

Arizona Arthritis and Rheumatology Research, PLLC

Phoenix, Arizona, 85032, United States

Location

California Allergy and Asthma Medical Group - CRN - PPDS 41230 11th Street West, Suite A

Palmdale, California, 93551, United States

Location

Inland Rheumatology Clinical Trials Incorporated

Upland, California, 91786, United States

Location

Rheumatology Consultant of Delaware dba Delaware Arthritis

Lewes, Delaware, 19958, United States

Location

MedBio Trials

Aventura, Florida, 33180, United States

Location

Clinical Research of West Florida Inc - Clearwater

Clearwater, Florida, 33765, United States

Location

Medical Research Center

Miami, Florida, 33144, United States

Location

AppleMed Research Group, LLC

Miami, Florida, 33155, United States

Location

Integral Rheumatology and Immunology Specialist, 140 Southwest 84th Avenue, Suite B

Plantation, Florida, 33324., United States

Location

Vicis Clinical Research INC

Tampa, Florida, 33615, United States

Location

Springfield Clinic (Clinic location)

Springfield, Illinois, 62702, United States

Location

Bluegrass Community Research Inc,330 Waller Avenue, Suite 100,

Lexington, Kentucky, 40504., United States

Location

Arthritis and Osteoporosis Associates

Freehold, New Jersey, 07728, United States

Location

Integrative Rheumatology

Charlotte, North Carolina, 28210, United States

Location

Altoona Center For Clinical Research, 175 Meadowbrook Lane,

Duncansville, Pennsylvania, 16635, United States

Location

Articularis Healthcare Group, Inc dba Low Country Rheumatology

Summerville, South Carolina, 29486, United States

Location

Accurate Clinical Management, LLC

Baytown, Texas, 77521, United States

Location

Trinity Clinical Research LLC, 2008 East Hebron Parkway, Suites 120/114/100,

Carrollton, Texas, 75010, United States

Location

Abigail Neiman

Houston, Texas, 77084, United States

Location

Accurate Clinical Management, LLC

Houston, Texas, 77084, United States

Location

Laila A Hassan, MD, PA

Houston, Texas, 77084, United States

Location

Accurate Clinical Research-Houston, 11003 Resource Parkway, Suite 102

Houston, Texas, 77089, United States

Location

Houston Rheumatology & Arthritis Specialists

Katy, Texas, 77494, United States

Location

Clinical Associates in Research Therapeutics of America, LLC

San Antonio, Texas, 78212, United States

Location

Accurate Clinical Research, Inc.

San Antonio, Texas, 78229, United States

Location

Accurate Clinical Research-League City

Texas City, Texas, 77034, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Head-Clinical Development
• Organization: Dr. Reddy's Laboratories Ltd.

RI-01-007@drreddys.com

91-40-4464-4000

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A randomized, double-blind, parallel group, multicenter study to assess the immunogenicity and safety of transitioning subjects with rheumatoid arthritis to biosimilar rituximab (DRL\_RI) or continued treatment with Rituxan® or MabThera®

Study Record Dates

• First Submitted: January 31, 2020
• First Posted: February 13, 2020
• Study Start: April 8, 2020
• Primary Completion: January 26, 2022
• Study Completion: April 20, 2022
• Last Updated: November 18, 2023
• Results First Posted: November 18, 2023

Record last verified: 2023-10

Locations

US (26)