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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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04268771
Recruitment Status : Active, not recruiting
First Posted : February 13, 2020
Last Update Posted : April 7, 2022
Sponsor:
Collaborator:
PPD
Information provided by (Responsible Party):
Dr. Reddy's Laboratories Limited

Tracking Information
First Submitted Date  ICMJE January 31, 2020
First Posted Date  ICMJE February 13, 2020
Last Update Posted Date April 7, 2022
Actual Study Start Date  ICMJE April 8, 2020
Actual Primary Completion Date January 26, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 11, 2020)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase III Transition Study of DRL Rituximab to Reference Medicinal Products
Official Title  ICMJE 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®
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.

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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
    Intervention: Biological: Experimental: Arm A: DRL_RI
  • 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.

    Intervention: Biological: Arm B: Rituxan®/Mabthera®
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 11, 2020)
140
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 29, 2022
Actual Primary Completion Date January 26, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04268771
Other Study ID Numbers  ICMJE RI-01-007
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Dr. Reddy's Laboratories Limited
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Dr. Reddy's Laboratories Limited
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE PPD
Investigators  ICMJE Not Provided
PRS Account Dr. Reddy's Laboratories Limited
Verification Date April 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP