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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Male or female subjects aged 18 years or older who have provided valid written informed consent. 2. 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. 3. 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. 4. 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. EXCLUSION CRITERIA; 1. Subjects with RA in functional Class IV 2. 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. 3. 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. 4. Active systemic infection. 5. Severely immunocompromised. 6. History of severe hypersensitivity to either US-rituximab or EU-rituximab or any of its excipients requiring drug discontinuation. 7. 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. 8. Any condition that in the opinion of the investigator represents an obstacle for study conduct and/or represents a potential unacceptable risk for subjects. 9. Requires treatment with any biological medicinal product during the study other than the study treatment. 10. Previous treatment with B-cell modulating or cell depleting biologic therapy except US-rituximab or EU-rituximab. 11. 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. 12. 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. 13. 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.
  • - Creatinine clearance (Cockcroft & Gault formula) of less than 50 mL/min.
14. History of vaccination with live vaccines within 4 weeks of the first dose of study treatment (Day 1) or known to require live vaccines during the study. 15. Lactating or pregnant female. 16. Women of childbearing potential who do not consent to use highly effective methods of birth control (e.g., barrier contraceptives, oral contraceptives, intrauterine devices, true abstinence if it allowed as per the country specific regulatory requirement [periodic abstinence {e.g., calendar ovulation, symptothermal, post-ovulation methods} and withdrawal are not acceptable methods of contraception], or sterilization) during treatment and for at least 12 months after the last administration of study treatment. 17. For men involved in any sexual intercourse that could lead to pregnancy, subjects must agree to use 1 of the highly effective methods of birth control listed in Exclusion Criterion #16 during treatment and for at least 12 months after the last administration of study treatment. 18. Subject with serum IgG < lower limit of normal.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04268771
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 3
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Dr. Reddy's Laboratories Limited
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

IndustryIndustry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Rheumatoid Arthritis
Additional Details

This is a randomized, double-blind, parallel group, multicenter, Phase 3 transition study in subjects with active RA who are eligible for the subsequent treatment course with US-rituximab or EU-rituximab according to the clinical judgment of the investigator. Subjects will then be randomized by interactive web response system (IWRS) to receive either two 1000 mg infusions of DRL_RI (Arm A) or US-rituximab/EU-rituximab (Arm B) on Day 1 and Day 15. Subjects randomized to Arm A will receive DRL_RI and subjects randomized to Arm B will continue to receive either US-rituximab or EU-rituximab. The study will consist of a screening period (Days -14 to 0) and a double-blind period (Day 1 to Week 12). Subjects will attend a screening visit followed by a visit at Weeks 0 (Day 1), 2, 4, 8, and 12 after randomization It is planned that approximately 50 sites will be initiated for this study in up to 7 countries (including but not restricted to United States). There has been no randomization of patients till date for this study. The study endpoints include: The immunogenicity endpoint is: • The incidence of anti-drug antibodies (ADA), including titer and neutralizing antibodies (NAb). The primary safety endpoints are:

  • - Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).
  • - Incidence of anaphylactic reactions, hypersensitivity reactions, and IRRs.

Arms & Interventions

Arms

Experimental: Arm A: DRL_RI

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

Active Comparator: Arm B: US-Rituximab or EU-Rituximab

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.

Interventions

Biological: - Experimental: Arm A: DRL_RI

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

Biological: - Arm B: Rituxan®/Mabthera®

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Palmdale, California

Status

Recruiting

Address

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

Palmdale, California, 93551

Site Contact

Ricardo Tan, MD

[email protected]

310-966-9022

Lewes, Delaware

Status

Recruiting

Address

Rheumatology Consultant of Delaware dba Delaware Arthritis

Lewes, Delaware, 19958

Site Contact

Jose A Pando, M.D.

[email protected]

+91 4044644500

AppleMed Research Group, LLC, Miami, Florida

Status

Recruiting

Address

AppleMed Research Group, LLC

Miami, Florida, 33155

Site Contact

Agustin J. Latorre, M.D.

[email protected]

305-667-8434

Plantation, Florida

Status

Recruiting

Address

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

Plantation, Florida, 33324.

Site Contact

Guillermo Valenzuela,, M.D.

[email protected]

954-476-2338 #211

Springfield Clinic (Clinic location), Springfield, Illinois

Status

Recruiting

Address

Springfield Clinic (Clinic location)

Springfield, Illinois, 62702

Site Contact

Robert Greig Trapp, M.D.

[email protected]

217-528-7541

Lexington, Kentucky

Status

Recruiting

Address

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

Lexington, Kentucky, 40504.

Site Contact

Jeffrey Neal, M.D.

[email protected]

859-351-5175

Duncansville, Pennsylvania

Status

Recruiting

Address

Altoona Center For Clinical Research, 175 Meadowbrook Lane,

Duncansville, Pennsylvania, 16635

Site Contact

Alan Kivitz, M.D.

[email protected]

814-693-0300 #157

Summerville, South Carolina

Status

Recruiting

Address

Articularis Healthcare Group, Inc dba Low Country Rheumatology

Summerville, South Carolina, 29486

Site Contact

Colin C. Edgerton, M.D.

[email protected]

843-572-1818

Accurate Clinical Management, LLC, Baytown, Texas

Status

Recruiting

Address

Accurate Clinical Management, LLC

Baytown, Texas, 77521

Site Contact

Sabeen Najam, M.D.

[email protected]

+91 4044644500

Carrollton, Texas

Status

Recruiting

Address

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

Carrollton, Texas, 75010

Site Contact

John Joseph, M.D.

[email protected]

972-492-8700

Accurate Clinical Management, LLC, Houston, Texas

Status

Recruiting

Address

Accurate Clinical Management, LLC

Houston, Texas, 77084

Site Contact

Amber Khan, M.D.

[email protected]

+91 4044644500

Houston, Texas

Status

Recruiting

Address

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

Houston, Texas, 77089

Site Contact

Philip Waller, M.D.

[email protected]

281-481-8557 #33

San Antonio, Texas

Status

Recruiting

Address

Clinical Associates in Research Therapeutics of America, LLC

San Antonio, Texas, 78212

Site Contact

Humayun Beg, M.D.

[email protected]

+91 4044644500

Accurate Clinical Research, Inc., San Antonio, Texas

Status

Recruiting

Address

Accurate Clinical Research, Inc.

San Antonio, Texas, 78229

Site Contact

Alex De Jesus, M.D.

[email protected]

210-762-6579