Comparative Pharmacokinetic, Pharmacodynamic, Safety and Efficacy Study of Three Anti-CD20 Monoclonal Antibodies in Patients With Moderate to Severe Rheumatoid Arthritis
1 other identifier
interventional
276
2 countries
28
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 rheumatoid-arthritis
Started Nov 2014
Longer than P75 for phase_1 rheumatoid-arthritis
28 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2014
CompletedFirst Submitted
Initial submission to the registry
November 18, 2014
CompletedFirst Posted
Study publicly available on registry
November 20, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
October 5, 2017
CompletedResults Posted
Study results publicly available
January 13, 2020
CompletedJanuary 13, 2020
December 1, 2019
2 years
November 18, 2014
August 28, 2019
December 27, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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.
2 weeks
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.
16 weeks
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
16 weeks
Secondary Outcomes (18)
Maximum Plasma Concentration (Cmax) After First Dose
2 weeks
Maximum Plasma Concentration (Cmax) After Second Dose
2 weeks
Time to Cmax (Tmax) After First Dose.
2 weeks
Time to Cmax (Tmax) After Second Dose
2 weeks
Volume of Distribution (Vz)
24 weeks
- +13 more secondary outcomes
Study Arms (3)
DRL_RI
EXPERIMENTALRituxan
ACTIVE COMPARATORMabThera
ACTIVE COMPARATORInterventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (28)
Gurunank Care Hospital
Hyderabad, Andhra Pradesh, 500020, India
Care Hospitals
Hyderabad, Andhra Pradesh, 500034, India
Krishna Institute of Medical Sciences Ltd.
Secunderabad, Andhra Pradesh, 500003, India
Yashoda Hospital
Secunderabad, Andhra Predesh, 500003, India
Shalby Hospitals
Ahmedabad, Gujarat, 380015, India
Government Medical College & New Civil Hospital
Surat, Gujarat, 395001, India
Chanre Rheumatology & Immunology Center & Research
Bangalore, Karnataka, 560079, India
Sushruta Multispeciality Hospital & Research Centre Pvt. Ltd
Hubli, Karnataka, 5880021, India
Jagadguru Sri Shivarathreeshwara Hospital
Mysore, Karnataka, 570004, India
Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute
Mumbai, Maharashtra, 400053, India
Jehangir Clinical Development Centre Pvt. Ltd.
Pune, Maharashtra, 411001, India
Deennath Mangeshkar Hospital and Research Centre
Pune, Maharashtra, 411004, India
Oyster & Pearl Hospital
Pune, Maharashtra, 411005, India
lnamdar Multispeciality Hospital
Pune, Maharashtra, 411040, India
Maulana Azad Medical College & Associated Lok Nayak Hospitals
New Delhi, National Capital Territory of Delhi, 110002, India
lndraprastha Apollo Hospitals
New Delhi, National Capital Territory of Delhi, 110076, India
Dayanand Medical College & Hosptial
Ludhiana, Punjab, 141001, India
S. R. Kalla Memorial Gastro & General Hospital
Jaipur, Rajasthan, 302001, India
Shri Nidaan Hospital & Hope Fertility Centre
Jaipur, Rajasthan, 302006, India
Apollo Specialty Hosptials
Madurai, Tamil Nadu, 625020, India
King George's Medical University
Lucknow, Uttar Pradesh, 226018, India
Communal Healthcare Institution Kharkiv City Clinical Hospital #8
Kharkiv, 61176, Ukraine
State Institution National Scientific Center Acad. Strazhesko Institute of Cardiology of National Academy of Medical Science
Kyiv, 03680, Ukraine
State Institution D.F. Chebotariov Institute of Gerontology of NAMS of Ukraine
Kyiv, 04114, Ukraine
M.V. Sklifosovskyi Poltava Regional Clinical Hospital
Poltava, 36011, Ukraine
Vinnytsia M.I. Pyrogov Regional Clinical Hospital
Vinnytsia, 21018, Ukraine
Medical Clinical Investigational Center MC LLC Health Clinic
Vinnytsia, 21029, Ukraine
Communal Institution Zaporzhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council
Zaporizhzhia, 69600, Ukraine
Related Publications (1)
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.
PMID: 32052313DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Ankit Ranpura, MD (Associate Director- Clinical Development)
- Organization
- Dr. Reddy's Laboratories Ltd, Biologics Survey No. 47, Bachupally Village, Bachupally Mandal, Medchal Malkajgiri District Telangana, India - 500 090
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 18, 2014
First Posted
November 20, 2014
Study Start
November 1, 2014
Primary Completion
November 1, 2016
Study Completion
October 5, 2017
Last Updated
January 13, 2020
Results First Posted
January 13, 2020
Record last verified: 2019-12