Back to resultsComparative Pharmacokinetic, Pharmacodynamic, Safety and Efficacy Study of Three Anti-CD20 Monoclonal Antibodies in Patients With Moderate to Severe Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
DRL_RI
Rituxan
MabThera
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid arthritis, Rituximab, Pharmacokinetics
Eligibility Criteria
Inclusion Criteria:
- Male or female patients, 18 to 65 years of age
- Diagnosis of RA, according to ACR criteria (1987), of at least 6 months duration
- At randomization, tender joint count ≥ 6 and swollen joint count ≥ 6
- Evidence of at least moderate disease activity
- Patients receiving oral or parenteral MTX with a dose of 15 to 25 mg per week when given alone or 10 to 25 mg per week in combination with additional non-biologic DMARD(s) for at least 6 months and on stable dose for at least 3 months
- Patients must be on a stable dose of folic acid or equivalent (≥5 mg per week)
- Chest X-ray not suggestive of any lung infections including pulmonary tuberculosis (TB)
- Contraception required per protocol
Exclusion Criteria:
Prior therapy with
- Rituximab, abatacept, tocilizumab, anakinra or an agent/antibody targeting CD20, CD19 or B cells
- Tumor necrosis factor (TNF) alfa antagonists or other biologic DMARDs
Other prior or concurrent therapies may also be excluded
- Any clinically relevant abnormality detected on screening history, physical examination, clinical laboratory, chest X-ray, or electrocardiogram (ECG), other than values consistent with RA
- Evidence of active, suspected or inadequately treated TB
- Positive serological test for hepatitis C virus antibodies, hepatitis B surface antigen, hepatitis B core antibody, or human immunodeficiency virus
- History of cardiovascular disease, history of stroke, or uncontrolled hypertension
- History of lymphoproliferative disease or organ allograft
- History of cancer (except for in situ cancer, excised, or limited stage, curatively treated cancer with no sign of disease for >5 years)
- History of allergy (medication history) to any of the compounds used in the study
- Pregnant or lactating women or women planning to become pregnant during the study
Sites / Locations
- Gurunank Care Hospital
- Care Hospitals
- Krishna Institute of Medical Sciences Ltd.
- Yashoda Hospital
- Maulana Azad Medical College & Associated Lok Nayak Hospitals
- lndraprastha Apollo Hospitals
- Shalby Hospitals
- Government Medical College & New Civil Hospital
- Chanre Rheumatology & Immunology Center & Research
- Sushruta Multispeciality Hospital & Research Centre Pvt. Ltd
- Jagadguru Sri Shivarathreeshwara Hospital
- Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute
- Jehangir Clinical Development Centre Pvt. Ltd.
- Deennath Mangeshkar Hospital and Research Centre
- Oyster & Pearl Hospital
- lnamdar Multispeciality Hospital
- Dayanand Medical College & Hosptial
- S. R. Kalla Memorial Gastro & General Hospital
- Shri Nidaan Hospital & Hope Fertility Centre
- Apollo Specialty Hosptials
- King George's Medical University
- Communal Healthcare Institution Kharkiv City Clinical Hospital #8
- State Institution National Scientific Center Acad. Strazhesko Institute of Cardiology of National Academy of Medical Science
- State Institution D.F. Chebotariov Institute of Gerontology of NAMS of Ukraine
- M.V. Sklifosovskyi Poltava Regional Clinical Hospital
- Vinnytsia M.I. Pyrogov Regional Clinical Hospital
- Medical Clinical Investigational Center MC LLC Health Clinic
- Communal Institution Zaporzhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
DRL_RI
Rituxan
MabThera
Arm Description
Outcomes
Primary Outcome Measures
Area Under the Concentration-Time Curve From Time 0 to 336 Hours (AUC0-336) Post First Dose
PK samples were collected pre-infusion; 3 hours post infusion; EOI; and at 1, 6, 24, 48, 168 hours post End of Infusion. A PK sample at 336 hours post EOI were also to be collected after the second dose.
AUC0-∞ Over the Entire Course of Therapy (2 Doses) From Day 1 Through Week 16.
PK samples were collected pre-infusion; 3 hours post infusion; EOI; and at 1, 6, 24, 48, 168 hours post End of Infusion. A PK sample at 336 hours post EOI were also to be collected after the second dose.
Area Under Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-t) (Second Dose).
PK samples were collected pre-infusion; 3 hours post infusion; EOI; and at 1, 6, 24, 48, 168 hours post End of Infusion. A PK sample at 336 hours post EOI were also to be collected after the second dose
Secondary Outcome Measures
Maximum Plasma Concentration (Cmax) After First Dose
Plasma concentration was measured at 0, 3, 4.25 (End of infusion (EOI)) ,1 (post- EOI), 6 (post-EOI) , 24 (post-EOI) , 48 (post-EOI) ,and 168 hours (post-EOI).
Maximum Plasma Concentration (Cmax) After Second Dose
Plasma concentration was measured at 0, 3, 4.25 (End of infusion (EOI)) ,1 (post- EOI),6 (post-EOI) , 24 (post-EOI) , 48 (post-EOI) , 168 (post-EOI), and 336 hours post EOI.
Time to Cmax (Tmax) After First Dose.
Plasma concentration was measured at 0, 3, 4.25 (End of infusion (EOI)) ,1 (post- EOI), 6 (post-EOI) , 24 (post-EOI) , 48 (post-EOI) , and 168 hours (post-EOI).
Time to Cmax (Tmax) After Second Dose
Plasma concentration was measured at 0, 3, 4.25 (End of infusion (EOI)) ,1 (post- EOI), 6 (post-EOI) , 24 (post-EOI) , 48 (post-EOI) , and 168 hours (post-EOI).
Volume of Distribution (Vz)
Plasma concentration was measured at 0, 3, 4.25 (End of infusion (EOI)) ,1 (post- EOI), 6 (post-EOI) , 24 (post-EOI) , 48 (post-EOI) , 168 (post-EOI), 336 hours (post-EOI), 4 weeks, 6 weeks, 8 weeks, 10 weeks, 14 weeks, 18 weeks, and 22 weeks relative to infusion.
Systemic Clearance (CL)
Plasma concentration was measured at 0, 3, 4.25 (End of infusion (EOI)) ,1 (post- EOI), 6 (post-EOI) , 24 (post-EOI) , 48 (post-EOI) , 168 (post-EOI), 336 hours (post-EOI), 4 weeks, 6 weeks, 8 weeks, 10 weeks, 14 weeks, 18 weeks, and 22 weeks relative to infusion.
Terminal Half-life (t1/2)
Plasma concentration was measured at 0, 3, 4.25 (End of infusion (EOI)) ,1 (post- EOI), 6 (post-EOI) , 24 (post-EOI) , 48 (post-EOI) , 168 (post-EOI), 336 hours (post-EOI), 4 weeks, 6 weeks, 8 weeks, 10 weeks, 14 weeks, 18 weeks, and 22 weeks relative to infusion.
Mean Change in Disease Activity Score-C Reactive Protein (DAS28-CRP) From Baseline Per Unit Time at Weeks 4
In clinical studies, Disease Activity Score (DAS) is used to assess improvement in disease activity in RA patients over time. The assessment involved an examination of 28 joints for swelling, tenderness, blood C-reactive protein (CRP), and a one on one consultation between the patient and healthcare professional. The results were combined to produce a score which indicated how active the RA was at that particular time. The disease activity is interpreted as low (DAS <2.6), mild (2.6 to <3.2), moderate (3.2 to <5.1), and severe with DAS > 5.1. A DAS score between 0 and 2.6 corresponds to remission. The analysis of DAS28-CRP was based on a generalized estimating equation model in RA patients with DAS28 score > 3.2. The mean change was calculated from two time points (Value at 4 weeks minus baseline value).
Mean Change in DAS28-CRP From Baseline Per Unit Time at 8 Weeks.
In clinical studies, Disease Activity Score (DAS) is used to assess improvement in disease activity in RA patients over time. The assessment involved an examination of 28 joints for swelling, tenderness, blood C-reactive protein (CRP), and a one on one consultation between the patient and healthcare professional. The results were combined to produce a score which indicated how active the RA was at that particular time. The disease activity is interpreted as low (DAS <2.6), mild (2.6 to <3.2), moderate (3.2 to <5.1), and severe with DAS > 5.1. A DAS score between 0 and 2.6 corresponds to remission. The analysis of DAS28-CRP was based on a generalized estimating equation model in RA patients with DAS28 score > 3.2. The mean change was calculated from two time points (Value at 8 weeks minus baseline value).
Mean Change in DAS28-CRP From Baseline Per Unit Time at Week 12.
In clinical studies, Disease Activity Score (DAS) is used to assess improvement in disease activity in RA patients over time. The assessment involved an examination of 28 joints for swelling, tenderness, blood C-reactive protein (CRP), and a one on one consultation between the patient and healthcare professional. The results were combined to produce a score which indicated how active the RA was at that particular time. The disease activity is interpreted as low (DAS <2.6), mild (2.6 to <3.2), moderate (3.2 to <5.1), and severe with DAS > 5.1. A DAS score between 0 and 2.6 corresponds to remission. The analysis of DAS28-CRP was based on a generalized estimating equation model in RA patients with DAS28 score > 3.2. The mean change was calculated from two time points (Value at 12 weeks minus baseline value).
Mean Change in Disease Activity Score- C Reactive Protein (DAS28-CRP) From Baseline Per Unit Time at Week 16.
In clinical studies, Disease Activity Score (DAS) is used to assess improvement in disease activity in RA patients over time. The assessment involved an examination of 28 joints for swelling, tenderness, blood C-reactive protein (CRP), and a one on one consultation between the patient and healthcare professional. The results were combined to produce a score which indicated how active the RA was at that particular time. The disease activity is interpreted as low (DAS <2.6), mild (2.6 to <3.2), moderate (3.2 to <5.1), and severe with DAS > 5.1. A DAS score between 0 and 2.6 corresponds to remission. The analysis of DAS28-CRP was based on a generalized estimating equation model in RA patients with DAS28 score > 3.2. The mean change was calculated from two time points (Value at 16 weeks minus baseline value).
Percentage of Patients With B-cell Counts 20% Below the Lower Limit of Normal
The time to depletion and repletion of peripheral blood cell counts (determined by CD19+ cell counts) as well as the B-cell counts at selected time points (taking into consideration the patient baseline count) were used to assess the PD of the study drugs.
Percentage of Patients With Peripheral B-cell Counts Depletion at Week 16.
Analysis of the PD parameter peripheral B-Cell count was performed by evaluating the 95% CI for the difference between treatment arms in the percentage of patients with B-cell depletion at 48 hours after dose 1, Week 16, and at Week 24. Percentage of patients with B-cell repletion at each evaluation time is also reported and descriptively compared.
Percentage of Patients With Peripheral B-cell Counts Depletion at Week 24.
Analysis of the PD parameter peripheral B-Cell count was performed by evaluating the 95% CI for the difference between treatment arms in the percentage of patients with B-cell depletion at 48 hours after dose 1, Week 16, and at Week 24. Percentage of patients with B-cell repletion at each evaluation time is also reported and descriptively compared.
Percentage of Patients With ACR20 at Week 24
Percentage of the patients with at least 20% improvement in counts of tender, swollen joints and in 3 of the following: patient's assessment of pain, patient's global assessment of disease activity, patient's assessment of physical function, the physician's global assessment of disease activity, and acute phase reactant. Adjusted response rates for the treatment arms using the logistic regression analysis including treatment, gender and region as fixed effects and patients as random effect in the model.
Percentage of Patients With ACR50 at Week 24
Percentage of the patients with at least 50% improvement in counts of tender, swollen joints and in 3 of the following: patient's assessment of pain, patient's global assessment of disease activity, patient's assessment of physical function, the physician's global assessment of disease activity, and acute phase reactant. Adjusted Response rates for the treatment arms using the logistic regression analysis including treatment, gender and region as fixed effects and patients as random effect in the model.
Percentage of Patients With ACR70 Response at Week 24
Percentage of the patients with at least 70% improvement in counts of tender, swollen joints and in 3 of the following: patient's assessment of pain, patient's global assessment of disease activity, patient's assessment of physical function, the physician's global assessment of disease activity, and acute phase reactant. Adjusted Response rates for the treatment arms using the logistic regression analysis including treatment, gender and region as fixed effects and patients as random effect in the model.
Change From Baseline in HAQ-DI at Week 24.
The health assessment questionnaire disability index (HAQ-DI) was assessed at Week 24. The disability assessment component of the HAQ, the HAQ-DI, assessed a patient's level of functional ability and included questions about fine movements of the upper extremities, locomotor activities of the lower extremities, and activities that involved both upper and lower extremities. There were 20 questions in 8 categories of functioning which represented a comprehensive set of functional activities-dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. The stem of each item asked over the past week "Were you able to" perform a particular task. The patient's responses were made on a scale from 0 (no disability) to 3 (completely disabled). Each category contained at least 2 specific component questions.
Physical function was measured using the HAQ-DI Scores, which range from 0-3, with lower scores reflecting better physical function and thus, less disability.
Full Information
NCT ID
NCT02296775
First Posted
November 18, 2014
Last Updated
December 27, 2019
Sponsor
Dr. Reddy's Laboratories Limited
1. Study Identification
Unique Protocol Identification Number
NCT02296775
Brief Title
Comparative Pharmacokinetic, Pharmacodynamic, Safety and Efficacy Study of Three Anti-CD20 Monoclonal Antibodies in Patients With Moderate to Severe Rheumatoid Arthritis
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Completed
Study Start Date
November 2014 (undefined)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
October 5, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dr. Reddy's Laboratories Limited
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study will compare the plasma pharmacokinetic profile and the change in disease activity score in patients with active rheumatoid arthritis following treatment with two 1000 mg doses of DRL_RI or one of two sources of rituximab (Rituxan® or MabThera®). Patients will also be monitored for safety, B cell depletion and recovery, and for the development of immune responses to the administered study drugs
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid arthritis, Rituximab, Pharmacokinetics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
276 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DRL_RI
Arm Type
Experimental
Arm Title
Rituxan
Arm Type
Active Comparator
Arm Title
MabThera
Arm Type
Active Comparator
Intervention Type
Biological
Intervention Name(s)
DRL_RI
Intervention Description
Two 1000 mg intravenous infusions, one each on Day 1 and Day 15
Intervention Type
Biological
Intervention Name(s)
Rituxan
Other Intervention Name(s)
Rituximab
Intervention Description
Two 1000 mg intravenous infusions, one each on Day 1 and Day 15
Intervention Type
Biological
Intervention Name(s)
MabThera
Other Intervention Name(s)
Rituximab
Intervention Description
Two 1000 mg intravenous infusions, one each on Day 1 and Day 15
Primary Outcome Measure Information:
Title
Area Under the Concentration-Time Curve From Time 0 to 336 Hours (AUC0-336) Post First Dose
Description
PK samples were collected pre-infusion; 3 hours post infusion; EOI; and at 1, 6, 24, 48, 168 hours post End of Infusion. A PK sample at 336 hours post EOI were also to be collected after the second dose.
Time Frame
2 weeks
Title
AUC0-∞ Over the Entire Course of Therapy (2 Doses) From Day 1 Through Week 16.
Description
PK samples were collected pre-infusion; 3 hours post infusion; EOI; and at 1, 6, 24, 48, 168 hours post End of Infusion. A PK sample at 336 hours post EOI were also to be collected after the second dose.
Time Frame
16 weeks
Title
Area Under Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-t) (Second Dose).
Description
PK samples were collected pre-infusion; 3 hours post infusion; EOI; and at 1, 6, 24, 48, 168 hours post End of Infusion. A PK sample at 336 hours post EOI were also to be collected after the second dose
Time Frame
16 weeks
Secondary Outcome Measure Information:
Title
Maximum Plasma Concentration (Cmax) After First Dose
Description
Plasma concentration was measured at 0, 3, 4.25 (End of infusion (EOI)) ,1 (post- EOI), 6 (post-EOI) , 24 (post-EOI) , 48 (post-EOI) ,and 168 hours (post-EOI).
Time Frame
2 weeks
Title
Maximum Plasma Concentration (Cmax) After Second Dose
Description
Plasma concentration was measured at 0, 3, 4.25 (End of infusion (EOI)) ,1 (post- EOI),6 (post-EOI) , 24 (post-EOI) , 48 (post-EOI) , 168 (post-EOI), and 336 hours post EOI.
Time Frame
2 weeks
Title
Time to Cmax (Tmax) After First Dose.
Description
Plasma concentration was measured at 0, 3, 4.25 (End of infusion (EOI)) ,1 (post- EOI), 6 (post-EOI) , 24 (post-EOI) , 48 (post-EOI) , and 168 hours (post-EOI).
Time Frame
2 weeks
Title
Time to Cmax (Tmax) After Second Dose
Description
Plasma concentration was measured at 0, 3, 4.25 (End of infusion (EOI)) ,1 (post- EOI), 6 (post-EOI) , 24 (post-EOI) , 48 (post-EOI) , and 168 hours (post-EOI).
Time Frame
2 weeks
Title
Volume of Distribution (Vz)
Description
Plasma concentration was measured at 0, 3, 4.25 (End of infusion (EOI)) ,1 (post- EOI), 6 (post-EOI) , 24 (post-EOI) , 48 (post-EOI) , 168 (post-EOI), 336 hours (post-EOI), 4 weeks, 6 weeks, 8 weeks, 10 weeks, 14 weeks, 18 weeks, and 22 weeks relative to infusion.
Time Frame
24 weeks
Title
Systemic Clearance (CL)
Description
Plasma concentration was measured at 0, 3, 4.25 (End of infusion (EOI)) ,1 (post- EOI), 6 (post-EOI) , 24 (post-EOI) , 48 (post-EOI) , 168 (post-EOI), 336 hours (post-EOI), 4 weeks, 6 weeks, 8 weeks, 10 weeks, 14 weeks, 18 weeks, and 22 weeks relative to infusion.
Time Frame
24 weeks
Title
Terminal Half-life (t1/2)
Description
Plasma concentration was measured at 0, 3, 4.25 (End of infusion (EOI)) ,1 (post- EOI), 6 (post-EOI) , 24 (post-EOI) , 48 (post-EOI) , 168 (post-EOI), 336 hours (post-EOI), 4 weeks, 6 weeks, 8 weeks, 10 weeks, 14 weeks, 18 weeks, and 22 weeks relative to infusion.
Time Frame
24 weeks
Title
Mean Change in Disease Activity Score-C Reactive Protein (DAS28-CRP) From Baseline Per Unit Time at Weeks 4
Description
In clinical studies, Disease Activity Score (DAS) is used to assess improvement in disease activity in RA patients over time. The assessment involved an examination of 28 joints for swelling, tenderness, blood C-reactive protein (CRP), and a one on one consultation between the patient and healthcare professional. The results were combined to produce a score which indicated how active the RA was at that particular time. The disease activity is interpreted as low (DAS <2.6), mild (2.6 to <3.2), moderate (3.2 to <5.1), and severe with DAS > 5.1. A DAS score between 0 and 2.6 corresponds to remission. The analysis of DAS28-CRP was based on a generalized estimating equation model in RA patients with DAS28 score > 3.2. The mean change was calculated from two time points (Value at 4 weeks minus baseline value).
Time Frame
Baseline and 4 weeks
Title
Mean Change in DAS28-CRP From Baseline Per Unit Time at 8 Weeks.
Description
In clinical studies, Disease Activity Score (DAS) is used to assess improvement in disease activity in RA patients over time. The assessment involved an examination of 28 joints for swelling, tenderness, blood C-reactive protein (CRP), and a one on one consultation between the patient and healthcare professional. The results were combined to produce a score which indicated how active the RA was at that particular time. The disease activity is interpreted as low (DAS <2.6), mild (2.6 to <3.2), moderate (3.2 to <5.1), and severe with DAS > 5.1. A DAS score between 0 and 2.6 corresponds to remission. The analysis of DAS28-CRP was based on a generalized estimating equation model in RA patients with DAS28 score > 3.2. The mean change was calculated from two time points (Value at 8 weeks minus baseline value).
Time Frame
Baseline and 8 weeks
Title
Mean Change in DAS28-CRP From Baseline Per Unit Time at Week 12.
Description
In clinical studies, Disease Activity Score (DAS) is used to assess improvement in disease activity in RA patients over time. The assessment involved an examination of 28 joints for swelling, tenderness, blood C-reactive protein (CRP), and a one on one consultation between the patient and healthcare professional. The results were combined to produce a score which indicated how active the RA was at that particular time. The disease activity is interpreted as low (DAS <2.6), mild (2.6 to <3.2), moderate (3.2 to <5.1), and severe with DAS > 5.1. A DAS score between 0 and 2.6 corresponds to remission. The analysis of DAS28-CRP was based on a generalized estimating equation model in RA patients with DAS28 score > 3.2. The mean change was calculated from two time points (Value at 12 weeks minus baseline value).
Time Frame
Baseline and 12 weeks
Title
Mean Change in Disease Activity Score- C Reactive Protein (DAS28-CRP) From Baseline Per Unit Time at Week 16.
Description
In clinical studies, Disease Activity Score (DAS) is used to assess improvement in disease activity in RA patients over time. The assessment involved an examination of 28 joints for swelling, tenderness, blood C-reactive protein (CRP), and a one on one consultation between the patient and healthcare professional. The results were combined to produce a score which indicated how active the RA was at that particular time. The disease activity is interpreted as low (DAS <2.6), mild (2.6 to <3.2), moderate (3.2 to <5.1), and severe with DAS > 5.1. A DAS score between 0 and 2.6 corresponds to remission. The analysis of DAS28-CRP was based on a generalized estimating equation model in RA patients with DAS28 score > 3.2. The mean change was calculated from two time points (Value at 16 weeks minus baseline value).
Time Frame
Baseline and 16 weeks
Title
Percentage of Patients With B-cell Counts 20% Below the Lower Limit of Normal
Description
The time to depletion and repletion of peripheral blood cell counts (determined by CD19+ cell counts) as well as the B-cell counts at selected time points (taking into consideration the patient baseline count) were used to assess the PD of the study drugs.
Time Frame
48 hours
Title
Percentage of Patients With Peripheral B-cell Counts Depletion at Week 16.
Description
Analysis of the PD parameter peripheral B-Cell count was performed by evaluating the 95% CI for the difference between treatment arms in the percentage of patients with B-cell depletion at 48 hours after dose 1, Week 16, and at Week 24. Percentage of patients with B-cell repletion at each evaluation time is also reported and descriptively compared.
Time Frame
16 weeks
Title
Percentage of Patients With Peripheral B-cell Counts Depletion at Week 24.
Description
Analysis of the PD parameter peripheral B-Cell count was performed by evaluating the 95% CI for the difference between treatment arms in the percentage of patients with B-cell depletion at 48 hours after dose 1, Week 16, and at Week 24. Percentage of patients with B-cell repletion at each evaluation time is also reported and descriptively compared.
Time Frame
24 weeks
Title
Percentage of Patients With ACR20 at Week 24
Description
Percentage of the patients with at least 20% improvement in counts of tender, swollen joints and in 3 of the following: patient's assessment of pain, patient's global assessment of disease activity, patient's assessment of physical function, the physician's global assessment of disease activity, and acute phase reactant. Adjusted response rates for the treatment arms using the logistic regression analysis including treatment, gender and region as fixed effects and patients as random effect in the model.
Time Frame
24 weeks
Title
Percentage of Patients With ACR50 at Week 24
Description
Percentage of the patients with at least 50% improvement in counts of tender, swollen joints and in 3 of the following: patient's assessment of pain, patient's global assessment of disease activity, patient's assessment of physical function, the physician's global assessment of disease activity, and acute phase reactant. Adjusted Response rates for the treatment arms using the logistic regression analysis including treatment, gender and region as fixed effects and patients as random effect in the model.
Time Frame
24 weeks
Title
Percentage of Patients With ACR70 Response at Week 24
Description
Percentage of the patients with at least 70% improvement in counts of tender, swollen joints and in 3 of the following: patient's assessment of pain, patient's global assessment of disease activity, patient's assessment of physical function, the physician's global assessment of disease activity, and acute phase reactant. Adjusted Response rates for the treatment arms using the logistic regression analysis including treatment, gender and region as fixed effects and patients as random effect in the model.
Time Frame
24 weeks
Title
Change From Baseline in HAQ-DI at Week 24.
Description
The health assessment questionnaire disability index (HAQ-DI) was assessed at Week 24. The disability assessment component of the HAQ, the HAQ-DI, assessed a patient's level of functional ability and included questions about fine movements of the upper extremities, locomotor activities of the lower extremities, and activities that involved both upper and lower extremities. There were 20 questions in 8 categories of functioning which represented a comprehensive set of functional activities-dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. The stem of each item asked over the past week "Were you able to" perform a particular task. The patient's responses were made on a scale from 0 (no disability) to 3 (completely disabled). Each category contained at least 2 specific component questions.
Physical function was measured using the HAQ-DI Scores, which range from 0-3, with lower scores reflecting better physical function and thus, less disability.
Time Frame
24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female patients, 18 to 65 years of age
Diagnosis of RA, according to ACR criteria (1987), of at least 6 months duration
At randomization, tender joint count ≥ 6 and swollen joint count ≥ 6
Evidence of at least moderate disease activity
Patients receiving oral or parenteral MTX with a dose of 15 to 25 mg per week when given alone or 10 to 25 mg per week in combination with additional non-biologic DMARD(s) for at least 6 months and on stable dose for at least 3 months
Patients must be on a stable dose of folic acid or equivalent (≥5 mg per week)
Chest X-ray not suggestive of any lung infections including pulmonary tuberculosis (TB)
Contraception required per protocol
Exclusion Criteria:
Prior therapy with
Rituximab, abatacept, tocilizumab, anakinra or an agent/antibody targeting CD20, CD19 or B cells
Tumor necrosis factor (TNF) alfa antagonists or other biologic DMARDs
Other prior or concurrent therapies may also be excluded
Any clinically relevant abnormality detected on screening history, physical examination, clinical laboratory, chest X-ray, or electrocardiogram (ECG), other than values consistent with RA
Evidence of active, suspected or inadequately treated TB
Positive serological test for hepatitis C virus antibodies, hepatitis B surface antigen, hepatitis B core antibody, or human immunodeficiency virus
History of cardiovascular disease, history of stroke, or uncontrolled hypertension
History of lymphoproliferative disease or organ allograft
History of cancer (except for in situ cancer, excised, or limited stage, curatively treated cancer with no sign of disease for >5 years)
History of allergy (medication history) to any of the compounds used in the study
Pregnant or lactating women or women planning to become pregnant during the study
Facility Information:
Facility Name
Gurunank Care Hospital
City
Hyderabad
State/Province
Andhra Pradesh
ZIP/Postal Code
500020
Country
India
Facility Name
Care Hospitals
City
Hyderabad
State/Province
Andhra Pradesh
ZIP/Postal Code
500034
Country
India
Facility Name
Krishna Institute of Medical Sciences Ltd.
City
Secunderabad
State/Province
Andhra Pradesh
ZIP/Postal Code
500003
Country
India
Facility Name
Yashoda Hospital
City
Secunderabad
State/Province
Andhra Predesh
ZIP/Postal Code
500003
Country
India
Facility Name
Maulana Azad Medical College & Associated Lok Nayak Hospitals
City
New Delhi
State/Province
Delhi
ZIP/Postal Code
110002
Country
India
Facility Name
lndraprastha Apollo Hospitals
City
New Delhi
State/Province
Delhi
ZIP/Postal Code
110076
Country
India
Facility Name
Shalby Hospitals
City
Ahmedabad
State/Province
Gujarat
ZIP/Postal Code
380015
Country
India
Facility Name
Government Medical College & New Civil Hospital
City
Surat
State/Province
Gujarat
ZIP/Postal Code
395001
Country
India
Facility Name
Chanre Rheumatology & Immunology Center & Research
City
Bangalore
State/Province
Karnataka
ZIP/Postal Code
560079
Country
India
Facility Name
Sushruta Multispeciality Hospital & Research Centre Pvt. Ltd
City
Hubli
State/Province
Karnataka
ZIP/Postal Code
5880021
Country
India
Facility Name
Jagadguru Sri Shivarathreeshwara Hospital
City
Mysore
State/Province
Karnataka
ZIP/Postal Code
570004
Country
India
Facility Name
Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute
City
Mumbai
State/Province
Maharashtra
ZIP/Postal Code
400053
Country
India
Facility Name
Jehangir Clinical Development Centre Pvt. Ltd.
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411001
Country
India
Facility Name
Deennath Mangeshkar Hospital and Research Centre
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411004
Country
India
Facility Name
Oyster & Pearl Hospital
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411005
Country
India
Facility Name
lnamdar Multispeciality Hospital
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411040
Country
India
Facility Name
Dayanand Medical College & Hosptial
City
Ludhiana
State/Province
Punjab
ZIP/Postal Code
141001
Country
India
Facility Name
S. R. Kalla Memorial Gastro & General Hospital
City
Jaipur
State/Province
Rajasthan
ZIP/Postal Code
302001
Country
India
Facility Name
Shri Nidaan Hospital & Hope Fertility Centre
City
Jaipur
State/Province
Rajasthan
ZIP/Postal Code
302006
Country
India
Facility Name
Apollo Specialty Hosptials
City
Madurai
State/Province
Tamil Nadu
ZIP/Postal Code
625020
Country
India
Facility Name
King George's Medical University
City
Lucknow
State/Province
Uttar Pradesh
ZIP/Postal Code
226018
Country
India
Facility Name
Communal Healthcare Institution Kharkiv City Clinical Hospital #8
City
Kharkiv
ZIP/Postal Code
61176
Country
Ukraine
Facility Name
State Institution National Scientific Center Acad. Strazhesko Institute of Cardiology of National Academy of Medical Science
City
Kyiv
ZIP/Postal Code
03680
Country
Ukraine
Facility Name
State Institution D.F. Chebotariov Institute of Gerontology of NAMS of Ukraine
City
Kyiv
ZIP/Postal Code
04114
Country
Ukraine
Facility Name
M.V. Sklifosovskyi Poltava Regional Clinical Hospital
City
Poltava
ZIP/Postal Code
36011
Country
Ukraine
Facility Name
Vinnytsia M.I. Pyrogov Regional Clinical Hospital
City
Vinnytsia
ZIP/Postal Code
21018
Country
Ukraine
Facility Name
Medical Clinical Investigational Center MC LLC Health Clinic
City
Vinnytsia
ZIP/Postal Code
21029
Country
Ukraine
Facility Name
Communal Institution Zaporzhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council
City
Zaporizhzhia
ZIP/Postal Code
69600
Country
Ukraine
12. IPD Sharing Statement
Citations:
PubMed Identifier
32052313
Citation
Haridas VM, Katta R, Nalawade A, Kharkar S, Zhdan V, Garmish O, Lopez-Lazaro L, Batra SS, Kankanwadi S. Pharmacokinetic Similarity and Comparative Pharmacodynamics, Safety, Efficacy, and Immunogenicity of DRL_RI Versus Reference Rituximab in Biologics-Naive Patients with Moderate-to-Severe Rheumatoid Arthritis: A Double-Blind, Randomized, Three-Arm Study. BioDrugs. 2020 Apr;34(2):183-196. doi: 10.1007/s40259-020-00406-1.
Results Reference
derived
Learn more about this trial
Comparative Pharmacokinetic, Pharmacodynamic, Safety and Efficacy Study of Three Anti-CD20 Monoclonal Antibodies in Patients With Moderate to Severe Rheumatoid Arthritis
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