Clinical trial NCT02296775: Comparative Pharmacokinetic, Pharmacodynamic, Safety and Efficacy Study of Three Anti-CD20 Monoclonal Antibodies in Patients With Moderate to Severe Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid arthritis
Rituximab
Pharmacokinetics
Lead sponsor: Dr. Reddy's Laboratories Limited
Sponsor class: INDUSTRY
First posted: 2014-11-20
Enrollment: 276
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

1. Male or female patients, 18 to 65 years of age
2. Diagnosis of RA, according to ACR criteria (1987), of at least 6 months duration
3. At randomization, tender joint count ≥ 6 and swollen joint count ≥ 6
4. Evidence of at least moderate disease activity
5. 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
6. Patients must be on a stable dose of folic acid or equivalent (≥5 mg per week)
7. Chest X-ray not suggestive of any lung infections including pulmonary tuberculosis (TB)
8. Contraception required per protocol

Exclusion Criteria:

1. 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
2. Any clinically relevant abnormality detected on screening history, physical examination, clinical laboratory, chest X-ray, or electrocardiogram (ECG), other than values consistent with RA
3. Evidence of active, suspected or inadequately treated TB
4. Positive serological test for hepatitis C virus antibodies, hepatitis B surface antigen, hepatitis B core antibody, or human immunodeficiency virus
5. History of cardiovascular disease, history of stroke, or uncontrolled hypertension
6. History of lymphoproliferative disease or organ allograft
7. History of cancer (except for in situ cancer, excised, or limited stage, curatively treated cancer with no sign of disease for \>5 years)
8. History of allergy (medication history) to any of the compounds used in the study
9. Pregnant or lactating women or women planning to become pregnant during the study

Primary outcomes:
measure: Area Under the Concentration-Time Curve From Time 0 to 336 Hours (AUC0-336) Post First Dose
timeFrame: 2 weeks
measure: AUC0-∞ Over the Entire Course of Therapy (2 Doses) From Day 1 Through Week 16.
timeFrame: 16 weeks
measure: Area Under Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-t) (Second Dose).
timeFrame: 16 weeks
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) After First Dose
timeFrame: 2 weeks
measure: Maximum Plasma Concentration (Cmax) After Second Dose
timeFrame: 2 weeks
measure: Time to Cmax (Tmax) After First Dose.
timeFrame: 2 weeks
measure: Time to Cmax (Tmax) After Second Dose
timeFrame: 2 weeks
measure: Volume of Distribution (Vz)
timeFrame: 24 weeks
measure: Systemic Clearance (CL)
timeFrame: 24 weeks
measure: Terminal Half-life (t1/2)
timeFrame: 24 weeks
measure: Mean Change in Disease Activity Score-C Reactive Protein (DAS28-CRP) From Baseline Per Unit Time at Weeks 4
timeFrame: Baseline and 4 weeks
measure: Mean Change in DAS28-CRP From Baseline Per Unit Time at 8 Weeks.
timeFrame: Baseline and 8 weeks
measure: Mean Change in DAS28-CRP From Baseline Per Unit Time at Week 12.
timeFrame: Baseline and 12 weeks
measure: Mean Change in Disease Activity Score- C Reactive Protein (DAS28-CRP) From Baseline Per Unit Time at Week 16.
timeFrame: Baseline and 16 weeks
measure: Percentage of Patients With B-cell Counts 20% Below the Lower Limit of Normal
timeFrame: 48 hours
measure: Percentage of Patients With Peripheral B-cell Counts Depletion at Week 16.
timeFrame: 16 weeks
measure: Percentage of Patients With Peripheral B-cell Counts Depletion at Week 24.
timeFrame: 24 weeks
measure: Percentage of Patients With ACR20 at Week 24
timeFrame: 24 weeks
measure: Percentage of Patients With ACR50 at Week 24
timeFrame: 24 weeks
measure: Percentage of Patients With ACR70 Response at Week 24
timeFrame: 24 weeks
measure: Change From Baseline in HAQ-DI at Week 24.
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Hyderabad
country: India
facility: Gurunank Care Hospital
state: Andhra Pradesh
city: Hyderabad
country: India
facility: Care Hospitals
state: Andhra Pradesh
city: Secunderabad
country: India
facility: Krishna Institute of Medical Sciences Ltd.
state: Andhra Pradesh
city: Secunderabad
country: India
facility: Yashoda Hospital
state: Andhra Predesh
city: New Delhi
country: India
facility: Maulana Azad Medical College & Associated Lok Nayak Hospitals
state: Delhi
city: New Delhi
country: India
facility: lndraprastha Apollo Hospitals
state: Delhi
city: Ahmedabad
country: India
facility: Shalby Hospitals
state: Gujarat
city: Surat
country: India
facility: Government Medical College & New Civil Hospital
state: Gujarat
city: Bangalore
country: India
facility: Chanre Rheumatology & Immunology Center & Research
state: Karnataka
city: Hubli
country: India
facility: Sushruta Multispeciality Hospital & Research Centre Pvt. Ltd
state: Karnataka
city: Mysore
country: India
facility: Jagadguru Sri Shivarathreeshwara Hospital
state: Karnataka
city: Mumbai
country: India
facility: Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute
state: Maharashtra
city: Pune
country: India
facility: Jehangir Clinical Development Centre Pvt. Ltd.
state: Maharashtra
city: Pune
country: India
facility: Deennath Mangeshkar Hospital and Research Centre
state: Maharashtra
city: Pune
country: India
facility: Oyster & Pearl Hospital
state: Maharashtra
city: Pune
country: India
facility: lnamdar Multispeciality Hospital
state: Maharashtra
city: Ludhiana
country: India
facility: Dayanand Medical College & Hosptial
state: Punjab
city: Jaipur
country: India
facility: S. R. Kalla Memorial Gastro & General Hospital
state: Rajasthan
city: Jaipur
country: India
facility: Shri Nidaan Hospital & Hope Fertility Centre
state: Rajasthan
city: Madurai
country: India
facility: Apollo Specialty Hosptials
state: Tamil Nadu
city: Lucknow
country: India
facility: King George's Medical University
state: Uttar Pradesh
city: Kharkiv
country: Ukraine
facility: Communal Healthcare Institution Kharkiv City Clinical Hospital #8
city: Kyiv
country: Ukraine
facility: State Institution National Scientific Center Acad. Strazhesko Institute of Cardiology of National Academy of Medical Science
city: Kyiv
country: Ukraine
facility: State Institution D.F. Chebotariov Institute of Gerontology of NAMS of Ukraine
city: Poltava
country: Ukraine
facility: M.V. Sklifosovskyi Poltava Regional Clinical Hospital
city: Vinnytsia
country: Ukraine
facility: Vinnytsia M.I. Pyrogov Regional Clinical Hospital
city: Vinnytsia
country: Ukraine
facility: Medical Clinical Investigational Center MC LLC Health Clinic
city: Zaporizhzhia
country: Ukraine
facility: Communal Institution Zaporzhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council
Study officials:
References:
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.