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A Phase III Transition Study of DRL Rituximab to Reference Medicinal Products (RI-01-007)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04268771
Recruitment Status : Recruiting
First Posted : February 13, 2020
Last Update Posted : May 28, 2020
Sponsor:
Collaborator:
PPD
Information provided by (Responsible Party):
Dr. Reddy's Laboratories Limited

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.


Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Biological: Experimental: Arm A: DRL_RI Biological: Arm B: Rituxan®/Mabthera® Phase 3

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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®
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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®
Actual Study Start Date : April 8, 2020
Estimated Primary Completion Date : May 28, 2021
Estimated Study Completion Date : May 28, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Rituximab

Arm Intervention/treatment
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
Biological: Experimental: Arm A: DRL_RI
Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion

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.

Biological: Arm B: Rituxan®/Mabthera®
Reference product US- rituximab (Rituxan®) or EU-rituximab (MabThera®), 100mg or 500mg, concentrate for solution for infusion




Primary Outcome Measures :
  1. Incidence of ADA on Day 1 [ Time Frame: ADA will be obtained before the administration of study treatment on Day 1 ]
    For Immunogenicity: Incidence of ADA, including titer and NAb

  2. Incidence of ADA on Day 15 [ Time Frame: ADA will be obtained before the administration of study treatment on Day 15 ]
    For Immunogenicity: Incidence of ADA, including titer and NAb

  3. Incidence of ADA at Week 4 [ Time Frame: ADA will be obtained before the administration of study treatment at Week 4 ]
    For Immunogenicity: Incidence of ADA, including titer and NAb

  4. Incidence of ADA at Week 8 [ Time Frame: ADA will be obtained before the administration of study treatment at Week 8 ]
    For Immunogenicity: Incidence of ADA, including titer and NAb

  5. Incidence of ADA at Week 12 (EOS/ET) visits [ Time Frame: ADA will be obtained before the administration of study treatment at Week 12 (EOS/ET) visits ]
    For Immunogenicity: Incidence of ADA, including titer and NAb

  6. Incidence of TEAEs on Day 1 [ Time Frame: Assessment of AE's will be carried out on Day 1 ]
    For Safety: Incidence of TEAEs: Treatment-emergent AE are defined as any AE occurring or worsening on or after the first dose of study medication.

  7. Incidence of TEAEs on Day 15 [ Time Frame: Assessment of AE's will be carried out during Day 15 ]
    For Safety: Incidence of TEAEs: Treatment-emergent AE are defined as any AE occurring or worsening on or after the first dose of study medication.

  8. Incidence of TEAEs at Week 4 ± 7 Days [ Time Frame: Assessment of AE's will be carried out at Week 4 ± 7 Days ]
    For Safety: Incidence of TEAEs: Treatment-emergent AE are defined as any AE occurring or worsening on or after the first dose of study medication.

  9. Incidence of TEAEs at Week 8 ± 7 Days [ Time Frame: Assessment of AE's will be carried out at Week 8 ± 7 Days ]
    For Safety: Incidence of TEAEs: Treatment-emergent AE are defined as any AE occurring or worsening on or after the first dose of study medication.

  10. Incidence of TEAEs at Week 12 ( EOS/ET) visits [ Time Frame: Assessment of AE's will be carried out at Week 12 (EOS/ET) visits ]
    For Safety: Incidence of TEAEs: Treatment-emergent AE are defined as any AE occurring or worsening on or after the first dose of study medication.

  11. Incidence of SAEs during screening [ Time Frame: Assessment of AE's will be carried out during screening ]
    For Safety: Incidence of SAEs: Results in death, is life-threatening, Requires in-subject hospitalization or prolongs existing hospitalization, Results in persistent or significant disability/incapacity.

  12. Incidence of SAEs on Day 1 [ Time Frame: Assessment of AE's will be carried out on Day 1 ]
    For Safety: Incidence of SAEs: Results in death, is life-threatening, Requires in-subject hospitalization or prolongs existing hospitalization, Results in persistent or significant disability/incapacity.

  13. Incidence of SAEs on Day 15 [ Time Frame: Assessment of AE's will be carried out on Day 15 ]
    For Safety: Incidence of SAEs: Results in death, is life-threatening, Requires in-subject hospitalization or prolongs existing hospitalization, Results in persistent or significant disability/incapacity.

  14. Incidence of SAEs at Week 4 ± 7 Days [ Time Frame: Assessment of AE's will be carried out at Week 4 ± 7 Days ]
    For Safety: Incidence of SAEs: Results in death, Is life-threatening, Requires in-subject hospitalization or prolongs existing hospitalization, Results in persistent or significant disability/incapacity.

  15. Incidence of SAEs at Week 8 ± 7 Days [ Time Frame: Assessment of AE's will be carried out at Week 8 ± 7 Days ]
    For Safety: Incidence of SAEs: Results in death, is life-threatening, Requires in-subject hospitalization or prolongs existing hospitalization, Results in persistent or significant disability/incapacity.

  16. Incidence of SAEs at Week 12 ( EOS/ET) Visits [ Time Frame: Assessment of AE's will be carried out at Week 12 (EOS/ET) visits ]
    For Safety: Incidence of SAEs: Results in death, is life-threatening, Requires in-subject hospitalization or prolongs existing hospitalization, Results in persistent or significant disability/incapacity.

  17. Incidence of Anaphylactic reactions during screening [ Time Frame: Assessments of Anaphylactic reactions will be carried out during screening ]
    Safety assessment will be done by measuring primary safety parameters anaphylactic reactions

  18. Incidence of Anaphylactic reactions on Day 1 [ Time Frame: Assessments of Anaphylactic reactions will be carried out on Day 1 ]
    Safety assessment will be done by measuring primary safety parameters anaphylactic reactions

  19. Incidence of Anaphylactic reactions on Day 15 [ Time Frame: Assessments of Anaphylactic reactions will be carried out on Day 15 ]
    Safety assessment will be done by measuring primary safety parameters anaphylactic reactions

  20. Incidence of Anaphylactic reactions at Week 4 ± 7 Days [ Time Frame: Assessments of Anaphylactic reactions will be carried out at Week 4 ± 7 Days ]
    Safety assessment will be done by measuring primary safety parameters anaphylactic reactions

  21. Incidence of Anaphylactic reactions at Week 8 ± 7 Days [ Time Frame: Assessments of Anaphylactic reactions will be carried out at Week 8 ± 7 Days ]
    Safety assessment will be done by measuring primary safety parameters anaphylactic reactions

  22. Incidence of Anaphylactic reactions at Week 12 ( EOS/ET) visits [ Time Frame: Assessments of Anaphylactic reactions will be carried out at Week 12 (EOS/ET) visits ]
    Safety assessment will be done by measuring primary safety parameters anaphylactic reactions

  23. Incidence of Hypersensitivity reactions during screening [ Time Frame: Assessments of Hypersensitivity reactions will be carried out during screening ]
    Safety assessment will be done by measuring primary safety parameters incidence of hypersensitivity reactions

  24. Incidence of Hypersensitivity reactions on Day 1 [ Time Frame: Assessments of hypersensitivity reactions will be carried out on Day 1 ]
    Safety assessment will be done by measuring primary safety parameters incidence of hypersensitivity reactions

  25. Incidence of Hypersensitivity reactions on Day 15 [ Time Frame: Assessments of hypersensitivity reactions will be carried out on Day 15 ]
    Safety assessment will be done by measuring primary safety parameters incidence of hypersensitivity reactions

  26. Incidence of Hypersensitivity reactions at Week 4 ± 7 Days [ Time Frame: Assessments of hypersensitivity reactions will be carried out at Week 4 ± 7 Days ]
    Safety assessment will be done by measuring primary safety parameters incidence of hypersensitivity reactions

  27. Incidence of Hypersensitivity reactions at Week 8 ± 7 Days [ Time Frame: Assessments of hypersensitivity reactions will be carried out at at Week 8 ± 7 Days ]
    Safety assessment will be done by measuring primary safety parameters incidence of hypersensitivity reactions

  28. Incidence of Hypersensitivity reactions at Week 12 ( EOS/ET) visits [ Time Frame: Assessments of hypersensitivity reactions will be carried out at Week 12 (EOS/ET) visits ]
    Safety assessment will be done by measuring primary safety parameters incidence of hypersensitivity reactions

  29. Incidence of Infusion-related reactions (IRRs) during screening [ Time Frame: Assessments of IRRs will be carried out during screening ]
    Safety assessment will be done by measuring primary safety parameters like IRRs

  30. Incidence of Infusion-related reactions (IRRs) on Day 1 [ Time Frame: Assessments of IRRs will be carried out on Day 1 ]
    Safety assessment will be done by measuring primary safety parameters like IRRs

  31. Incidence of Infusion-related reactions (IRRs) on Day 15 [ Time Frame: Assessments of IRRs will be carried out on Day 15 ]
    Safety assessment will be done by measuring primary safety parameters like IRRs

  32. Incidence of Infusion-related reactions (IRRs) at Week 4 ± 7 Days [ Time Frame: Assessment will be carried out at Week 4 ± 7 Days ]
    Safety assessment will be done by measuring primary safety parameters like IRRs

  33. Incidence of Infusion-related reactions (IRRs) at Week 8 ± 7 Days [ Time Frame: Assessments of IRRs will be carried out at Week 8 ± 7 Days ]
    Safety assessment will be done by measuring primary safety parameters like IRRs

  34. Incidence of Infusion-related reactions (IRRs) at Week 12 ( EOS/ET) visits [ Time Frame: Assessments of IRRs will be carried out at Week 12 (EOS/ET) visits ]
    Safety assessment will be done by measuring primary safety parameters like IRRs



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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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): NCT04268771


Contacts
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Contact: Dr. Narendra Maharaj, MBBS, MD +91 4044644500 narendramaharaj@drreddys.com
Contact: Dr. Sonica Sachdeva Batra, MD, DNB + 91 4044644500 sonicabatra@drreddys.com

Locations
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United States, California
California Allergy and Asthma Medical Group - CRN - PPDS 41230 11th Street West, Suite A Recruiting
Palmdale, California, United States, 93551
Contact: Ricardo Tan, MD    310-966-9022    ricardoatan@aol.com   
Contact: Richard Hyman    (310) 207-3320    rmhyman1947@gmail.com   
United States, Delaware
Rheumatology Consultant of Delaware dba Delaware Arthritis Recruiting
Lewes, Delaware, United States, 19958
Contact: Jose A Pando, M.D.         
Sub-Investigator: Jennifer Rahn, PA-C         
United States, Florida
AppleMed Research Group, LLC Recruiting
Miami, Florida, United States, 33155
Contact: Agustin J. Latorre, M.D.    305-667-8434    Dr.Latorre@applemedresearch.org   
Sub-Investigator: Rigoberto P. Reguero, M.D.         
Integral Rheumatology and Immunology Specialist, 140 Southwest 84th Avenue, Suite B Recruiting
Plantation, Florida, United States, 33324.
Contact: Guillermo Valenzuela,, M.D.    954-476-2338 ext 211    drvalenzuela@aol.com   
Contact: Marilu Colon-Soto    (954) 476-2338      
United States, Illinois
Springfield Clinic (Clinic location) Recruiting
Springfield, Illinois, United States, 62702
Contact: Robert Greig Trapp, M.D.    217-528-7541      
Sub-Investigator: Jason Paul Guthrie, M.D.         
Sub-Investigator: Jeffrey Robert Horvath, M.D.         
Sub-Investigator: Michael A. Pick, M.D.         
Sub-Investigator: Mark A. Stern, M.D.         
United States, Kentucky
Bluegrass Community Research Inc,330 Waller Avenue, Suite 100, Recruiting
Lexington, Kentucky, United States, 40504.
Contact: Jeffrey Neal, M.D.    859-351-5175    jneal@aclky.com   
Contact: Corey Hatfield    (859) 351-5175    chatfield@aclky.com   
United States, Pennsylvania
Altoona Center For Clinical Research, 175 Meadowbrook Lane, Recruiting
Duncansville, Pennsylvania, United States, 16635
Contact: Alan Kivitz, M.D.    814-693-0300 ext 157    ajkivitz@yahoo.com   
Contact: Frederick Murphy    (814) 693-0300    LRiley@altoonaresearch.com   
United States, South Carolina
Articularis Healthcare Group, Inc dba Low Country Rheumatology Recruiting
Summerville, South Carolina, United States, 29486
Contact: Colin C. Edgerton, M.D.    843-572-1818    edgerton2860@gmail.com   
Sub-Investigator: Jennifer K. Murphy, M.D.         
Sub-Investigator: Gary E. Fink, M.D.         
Sub-Investigator: Clarence W Legerton III, M.D.         
Sub-Investigator: Nicholas Holdgate, M.D.         
Sub-Investigator: Gregory W . Niemer, M.D.         
Sub-Investigator: Jacqueline Nguyen, CCRP         
United States, Texas
Accurate Clinical Management, LLC Recruiting
Baytown, Texas, United States, 77521
Contact: Sabeen Najam, M.D.       snajammd@accurateclinicalresearch.com   
Sub-Investigator: Amber Khan, M.D.         
Sub-Investigator: Omar Saab         
Sub-Investigator: Loreta Soneira         
Trinity Clinical Research LLC, 2008 East Hebron Parkway, Suites 120/114/100, Recruiting
Carrollton, Texas, United States, 75010
Contact: John Joseph, M.D.    972-492-8700    drjoseph.trinity@yahoo.com   
Contact: Mohan Penmetcha    (972) 492-8700    mpenmetcha@aol.com   
Accurate Clinical Management, LLC Recruiting
Houston, Texas, United States, 77084
Contact: Amber Khan, M.D.       akhanmd@accurateclinicalresearch.com   
Sub-Investigator: Sabeen Najam, M.D.         
Sub-Investigator: Emily Birdshead         
Sub-Investigator: Mohanad AIBayyaa         
Accurate Clinical Research-Houston, 11003 Resource Parkway, Suite 102 Recruiting
Houston, Texas, United States, 77089
Contact: Philip Waller, M.D.    281-481-8557 ext 33    pwallermd@accurateclinicalresearch.com   
Contact: Bradley Lamach    (281) 240-1045    blamach@accurateclinicalresearch.com   
Clinical Associates in Research Therapeutics of America, LLC Recruiting
San Antonio, Texas, United States, 78212
Contact: Humayun Beg, M.D.       humayunbeg@hotmail.com   
Sub-Investigator: Jaime Mayoral, M.D.         
Accurate Clinical Research, Inc. Recruiting
San Antonio, Texas, United States, 78229
Contact: Alex De Jesus, M.D.    210-762-6579    adejesusmd@accurateclinicalresearch.com   
Sub-Investigator: Lisa Sanchez         
Sub-Investigator: Michael Valdes         
Sponsors and Collaborators
Dr. Reddy's Laboratories Limited
PPD
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Responsible Party: Dr. Reddy's Laboratories Limited
ClinicalTrials.gov Identifier: NCT04268771    
Other Study ID Numbers: RI-01-007
First Posted: February 13, 2020    Key Record Dates
Last Update Posted: May 28, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents