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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 April 2022
• Main ID: NCT04268771
• Date of registration: 31/01/2020
• Prospective Registration: Yes
• Primary sponsor: Dr. Reddy's Laboratories Limited
• Public title: A Phase III Transition Study of DRL Rituximab to Reference Medicinal Products RI-01-007
• Scientific 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®
• Date of first enrolment: April 8, 2020
• Target sample size: 140
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT04268771
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

United States

Key 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Biological: Arm B: Rituxan®/Mabthera®

Biological: Experimental: Arm A: DRL_RI

Primary Outcome(s)

Incidence of ADA on Day 1 [Time Frame: ADA will be obtained before the administration of study treatment on Day 1]

Incidence of Hypersensitivity reactions on Day 15 [Time Frame: Assessments of hypersensitivity reactions will be carried out on Day 15]

Incidence of Infusion-related reactions (IRRs) at Week 4 ± 7 Days [Time Frame: Assessment will be carried out at Week 4 ± 7 Days]

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]

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]

Incidence of Anaphylactic reactions at Week 8 ± 7 Days [Time Frame: Assessments of Anaphylactic reactions will be carried out at Week 8 ± 7 Days]

Incidence of Anaphylactic reactions during screening [Time Frame: Assessments of Anaphylactic reactions will be carried out during screening]

Incidence of SAEs during screening [Time Frame: Assessment of AE's will be carried out during screening]

Incidence of TEAEs on Day 15 [Time Frame: Assessment of AE's will be carried out during Day 15]

Incidence of Anaphylactic reactions on Day 15 [Time Frame: Assessments of Anaphylactic reactions will be carried out on Day 15]

Incidence of ADA at Week 4 [Time Frame: ADA will be obtained before the administration of study treatment at Week 4]

Incidence of ADA on Day 15 [Time Frame: ADA will be obtained before the administration of study treatment on Day 15]

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]

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]

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]

Incidence of Infusion-related reactions (IRRs) during screening [Time Frame: Assessments of IRRs will be carried out during screening]

Incidence of SAEs at Week 8 ± 7 Days [Time Frame: Assessment of AE's will be carried out at Week 8 ± 7 Days]

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]

Incidence of Anaphylactic reactions on Day 1 [Time Frame: Assessments of Anaphylactic reactions will be carried out on Day 1]

Incidence of Hypersensitivity reactions during screening [Time Frame: Assessments of Hypersensitivity reactions will be carried out during screening]

Incidence of Hypersensitivity reactions on Day 1 [Time Frame: Assessments of hypersensitivity reactions will be carried out on Day 1]

Incidence of Infusion-related reactions (IRRs) on Day 1 [Time Frame: Assessments of IRRs will be carried out on Day 1]

Incidence of Infusion-related reactions (IRRs) on Day 15 [Time Frame: Assessments of IRRs will be carried out on Day 15]

Incidence of SAEs at Week 4 ± 7 Days [Time Frame: Assessment of AE's will be carried out at Week 4 ± 7 Days]

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]

Incidence of Anaphylactic reactions at Week 4 ± 7 Days [Time Frame: Assessments of Anaphylactic reactions will be carried out at Week 4 ± 7 Days]

Incidence of Hypersensitivity reactions at Week 4 ± 7 Days [Time Frame: Assessments of hypersensitivity reactions will be carried out at Week 4 ± 7 Days]

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]

Incidence of SAEs on Day 15 [Time Frame: Assessment of AE's will be carried out on Day 15]

Incidence of TEAEs at Week 4 ± 7 Days [Time Frame: Assessment of AE's will be carried out at Week 4 ± 7 Days]

Incidence of TEAEs at Week 8 ± 7 Days [Time Frame: Assessment of AE's will be carried out at Week 8 ± 7 Days]

Incidence of TEAEs on Day 1 [Time Frame: Assessment of AE's will be carried out on Day 1]

Incidence of ADA at Week 8 [Time Frame: ADA will be obtained before the administration of study treatment at Week 8]

Incidence of SAEs on Day 1 [Time Frame: Assessment of AE's will be carried out on Day 1]

Secondary ID(s)

RI-01-007

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

PPD