A Phase III Transition Study of DRL Rituximab to Referenc... | NCT04268771

NCT04268771

Status Module

Sponsor/Collaborators Module

Name	Class
PPD Development, LP	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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®

Name	Type	Description	Arm Group Labels	Other Names
Experimental: Arm A: DRL_RI	Biological	Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion	Arm A: DRL_RI

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
Number of Subjects Reporting Anaphylactic Reactions at Dosing Time Points (Either at Week 1 or Week 3)	Number of Subjects reporting anaphylactic reactions during the study drug administration either at Week 1 or Week 3 was reported	Assessments of Anaphylactic reactions will be carried out at either Week 1 or Week 3

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.

EXCLUSION CRITERIA;

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.
- Creatinine clearance (Cockcroft & Gault formula) of less than 50 mL/min.
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.
Lactating or pregnant female.
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.
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.
Subject with serum IgG < lower limit of normal.

Contacts/Locations Module

Locations

Facility	Status	City	State	ZIP	Country	Contacts
Arizona Arthritis and Rheumatology Research, PLLC		Phoenix	Arizona	85032	United States
California Allergy and Asthma Medical Group - CRN - PPDS 41230 11th Street West, Suite A

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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 Experimental: Arm A: DRL_RI: Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 10, 2020	Sep 28, 2023

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

Baseline analysis population include all the randomized study Participants

Arm/Group Information

ID	Title	Description
BG000	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 Experimental: Arm A: DRL_RI: Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion
BG001	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. Arm B: Rituxan®/Mabthera®: Reference product US- rituximab (Rituxan®) or EU-rituximab (MabThera®), 100mg or 500mg, concentrate for solution for infusion
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Study Participants

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Sex: Female, Male

Study Participants

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00054 BG00161 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0007 BG0015 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

study participants regional distribution globally was reported here

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00023 BG00122 BG002

Time from prior rituximab

The time period in months for which duration the subjects had received the reference treatment (Rituxan or MabThera)

Mean

Standard Deviation

months

Title

Denominators

Categories

Title	Measurements
	BG0007.5± 2.65 BG0017.6± 2.85

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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 Experimental: Arm A: DRL_RI: Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion
OG001	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. Arm B: Rituxan®/Mabthera®: Reference product US- rituximab (Rituxan®) or EU-rituximab (MabThera®), 100mg or 500mg, concentrate for solution for infusion

Units	Counts
Participants	OG00069 OG00168

Title

Denominators

Categories

Title	Measurements
	OG0003 OG0011

Primary

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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 Experimental: Arm A: DRL_RI: Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion
OG001	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. Arm B: Rituxan®/Mabthera®: Reference product US- rituximab (Rituxan®) or EU-rituximab (MabThera®), 100mg or 500mg, concentrate for solution for infusion

Primary

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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 Experimental: Arm A: DRL_RI: Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion
OG001	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. Arm B: Rituxan®/Mabthera®: Reference product US- rituximab (Rituxan®) or EU-rituximab (MabThera®), 100mg or 500mg, concentrate for solution for infusion

Primary

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

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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 Experimental: Arm A: DRL_RI: Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion
OG001	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. Arm B: Rituxan®/Mabthera®: Reference product US- rituximab (Rituxan®) or EU-rituximab (MabThera®), 100mg or 500mg, concentrate for solution for infusion

Primary

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

Posted

Count of Participants

Participants

ADA will be obtained at Week 12

ID	Title	Description
OG000	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 Experimental: Arm A: DRL_RI: Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion
OG001	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. Arm B: Rituxan®/Mabthera®: Reference product US- rituximab (Rituxan®) or EU-rituximab (MabThera®), 100mg or 500mg, concentrate for solution for infusion

Secondary

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

Number of Subjects reporting anaphylactic reactions during the study drug administration either at Week 1 or Week 3 was reported

Safety population

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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 Experimental: Arm A: DRL_RI: Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion
OG001	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. Arm B: Rituxan®/Mabthera®: Reference product US- rituximab (Rituxan®) or EU-rituximab (MabThera®), 100mg or 500mg, concentrate for solution for infusion

Secondary

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

TEAEs (Treatment emergent adverse events) which lead to study subjects discontinuation from the study drug administration at either week 1 or week 3 dosing timepoint

Safety population

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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 Experimental: Arm A: DRL_RI: Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion
OG001	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. Arm B: Rituxan®/Mabthera®: Reference product US- rituximab (Rituxan®) or EU-rituximab (MabThera®), 100mg or 500mg, concentrate for solution for infusion

Secondary

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

Incidence of SAEs: SAE is defined as "Results in death, is life-threatening, Requires in-subject hospitalization or prolongs existing hospitalization, Results in persistent or significant disability/incapacity".

The measure here is only subjects reporting SAE.

Safety population

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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 Experimental: Arm A: DRL_RI: Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion
OG001	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. Arm B: Rituxan®/Mabthera®: Reference product US- rituximab (Rituxan®) or EU-rituximab (MabThera®), 100mg or 500mg, concentrate for solution for infusion

Secondary

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

Number of TEAEs: Treatment-emergent AE are defined as any AE occurring or worsening on or after the first dose of study medication.

Safety population

Posted

Number

Number of events

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

Events

ID	Title	Description
OG000	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 Experimental: Arm A: DRL_RI: Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion
OG001	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. Arm B: Rituxan®/Mabthera®: Reference product US- rituximab (Rituxan®) or EU-rituximab (MabThera®), 100mg or 500mg, concentrate for solution for infusion

Secondary

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

number of subjects reporting AE in the overall study are defined as any AE occurring or worsening after the ICF signed in the study

Safety population

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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 Experimental: Arm A: DRL_RI: Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion
OG001	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. Arm B: Rituxan®/Mabthera®: Reference product US- rituximab (Rituxan®) or EU-rituximab (MabThera®), 100mg or 500mg, concentrate for solution for infusion

Secondary

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

Number of subjects reporting Treatment-emergent AE (TEAEs) are defined as any AE occurring or worsening on or after the first dose of study medication.

Safety population

Posted

Count of Participants

Participants

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

ID	Title	Description
OG000	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 Experimental: Arm A: DRL_RI: Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion
OG001	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. Arm B: Rituxan®/Mabthera®: Reference product US- rituximab (Rituxan®) or EU-rituximab (MabThera®), 100mg or 500mg, concentrate for solution for infusion

Secondary

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

Safety assessment will be done by measuring hypersensitivity reactions at Dosing Time Points (Either at Week 1 or Week 3)

Posted

Number

participants

Assessments of hypersensitivity reactions either at Week 1 or Week 3

ID	Title	Description
OG000	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 Experimental: Arm A: DRL_RI: Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion
OG001	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. Arm B: Rituxan®/Mabthera®: Reference product US- rituximab (Rituxan®) or EU-rituximab (MabThera®), 100mg or 500mg, concentrate for solution for infusion

Secondary

Number of Subjects Reporting Infusion-related Reactions (IRRs) at Dosing Time Points (Either at Week 1 or Week 3)

Safety assessment: Number of Subjects Reporting Infusion-related reactions (IRRs) at Dosing Time Points (Either at Week 1 or Week 3) was reported

Safety population

Posted

Number

participants

Assessments of IRRs were carried out at either Week 1 or Week 3

ID	Title	Description
OG000	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 Experimental: Arm A: DRL_RI: Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion
OG001	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. Arm B: Rituxan®/Mabthera®: Reference product US- rituximab (Rituxan®) or EU-rituximab (MabThera®), 100mg or 500mg, concentrate for solution for infusion

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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 Experimental: Arm A: DRL_RI: Proposed rituximab biosimilar, 100mg or 500mg, concentrate for solution for infusion	4	70	4	70	3	70
EG001	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. Arm B: Rituxan®/Mabthera®: Reference product US- rituximab (Rituxan®) or EU-rituximab (MabThera®), 100mg or 500mg, concentrate for solution for infusion	2	70	2	70	17	70

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Myocardial Infarction	Cardiac disorders	Systematic Assessment	EG0001 events1 affected70 at risk EG0010 events0 affected70 at risk
Intestinal resection	Surgical and medical procedures	Systematic Assessment	EG0001 events1 affected70 at risk EG0010 events0 affected70 at risk
Embolic stroke	Nervous system disorders	Systematic Assessment	EG0000 events0 affected70 at risk EG0011 events1 affected70 at risk
Enteritis	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected70 at risk EG0011 events1 affected70 at risk
COVID-19 Pneumonia	Infections and infestations	Systematic Assessment	EG0002 events2 affected70 at risk EG0010 events0 affected70 at risk
Cystitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected70 at risk EG0011 events1 affected70 at risk
Empyema	Infections and infestations	Systematic Assessment	EG0000 events0 affected70 at risk EG0011 events1 affected70 at risk
Septic Shock	Infections and infestations	Systematic Assessment	EG0000 events0 affected70 at risk EG0011 events1 affected70 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Headache	Nervous system disorders	Systematic Assessment	EG0000 events0 affected70 at risk EG0015 events5 affected70 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected70 at risk EG0015 events5 affected70 at risk
COVID-19	Infections and infestations	Systematic Assessment	EG0001 events1 affected70 at risk EG0014 events4 affected70 at risk
Nasopharyngitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected70 at risk EG0013 events3 affected70 at risk

First MCP Posted Date

ID	Term
D001172	Arthritis, Rheumatoid

Ancestor Terms

ID	Term
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

Units	Counts
Participants	OG00069 OG00168

Units	Counts
Participants	OG00069 OG00168

Units	Counts
Participants	OG00069 OG00168

Units	Counts
Participants	OG00069 OG00168