Comparative Pharmacokinetic Study of Three Abatacept Products in Male Normal Healthy Volunteers by the Subcutaneous Route

NCT06126042 | Unknown Phase 1 FDA Drug

• 1 other identifier: AB-01-001
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 3

Brief Summary

This is a randomised, double-blind, single dose, parallel groups study to compare the PK, immunogenicity, and safety of 3 abatacept products (DRL\_AB, RP and RMP) in male NHV.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (2)

• Single-dose pharmacokinetic parameter Area under the serum concentration-time curve from time zero extrapolated to infinity [AUC(INF)] will be derived from serum concentration versus time data [Time frame over 85 days as mentioned]

  Pharmacokinetic parameters - AUC (0-∞)

  1hour prior to the drug administration and at hours 1,4,12,24,36,48,60,72,84,96,108,120,132,144,156,168,216, post study drug administration & on days 15, 22, 29, 36, 43, 50, 57,71, 85 (End Of Study)

• Single-dose pharmacokinetic parameter Maximum observed serum concentration (Cmax) will be derived from serum concentration versus time data [Time frame over 85 days]

  Pharmacokinetic parameters - Cmax

  1hour prior to the drug administration, at hours 1,4,12,24,36,48, 60,72,84,96,108,120,132,144,156,168,216 post study drug administration & on days 15, 22, 29, 36, 43, 50, 57,71,85 (End Of Study)

Secondary Outcomes (20)

• Area under the serum concentration-time curve from zero to the last time of the last quantifiable concentration will be derived from serum concentration versus time data

  1hour prior to the drug administration till Day 85 (End Of Study)

• Time to reach Cmax in serum of will be derived from serum concentration versus time data

  1hour prior to the drug administration till Day 85 (End Of Study)

• apparent terminal decline rate constant λz

  1hour prior to the drug administration till Day 85 (End Of Study)

• t1/2

  1hour prior to the drug administration till Day 85 (End Of Study)

• CL/f

  1hour prior to the drug administration till Day 85 (End Of Study)

Study Arms (3)

DRL_AB

EXPERIMENTAL

Drug: Abatacept Prefilled Syringe Each pre-filled syringe contains 125 mg of abatacept in 1 mL Other Name: Dr. Reddy's Abatacept

Drug: Test Product

RP

ACTIVE COMPARATOR

Drug: Abatacept Prefilled Syringe Each pre-filled syringe contains 125 mg of abatacept in 1 mL Other Names: Orencia

Drug: Reference product

RMP

ACTIVE COMPARATOR

Drug: Abatacept Prefilled Syringe Each pre-filled syringe contains 125 mg of abatacept in 1 mL Other Names: Orencia

Drug: Reference Medicinal Product

Interventions

Test Product DRUG

DRL\_AB, Pre Filled Syringe; Solution for injection

Also known as: Proposed Biosimilar

DRL_AB

Reference product DRUG

USA licenced ORENCIA®, Pre Filled Syringe; Solution for injection

Also known as: US Orencia

RP

Reference Medicinal Product DRUG

EU approved ORENCIA®, Pre Filled Syringe; Solution for injection

Also known as: EU Orencia

RMP

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: The current study will be performed only in male subjects to avert gender-related variability.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy Male volunteers, 18 to 50 years of age (both age inclusive), at the time of signing informed consent.
• In general, good health as determined by a qualified physician based on a comprehensive medical history, physical examination including vital signs, laboratory haematology, clinical chemistry, urinalysis and 12-lead electrocardiogram (ECG) before randomisation.
• Body mass index between 18.5-30.0 kg/m2 (both inclusive) and body weight of 60.0 - 100.0 kg (both inclusive; stratified as 60.0 to \<80 kg and ≥80.0 to 100.0 Kg).
• Subjects or their female partner (if they are women of childbearing potential \[WOCBP\]) must be willing to use at least 1 highly effective method of contraception as described below from the time of study drug administration until 3 months after dosing. Subjects should also refrain from sperm donation during the period from the time of study drug administration until 3 months after dosing. Highly effective birth control measures per Clinical Trials Facilitation and coordination Group (CTFG) guidelines (adopted and implemented on 21/09/2020) include the following:
• For a subject:
• Permanently sterile by bilateral orchidectomy;
• Sexual abstinence.
• For the female partner of a male subject:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation - oral, intravaginal, and transdermal;
• Progestogen-only hormonal contraception associated with inhibition of ovulation - oral, injectable, implantable;
• Intrauterine device;
• Intrauterine hormone-releasing system;
• Bilateral tubal occlusion;
• Vasectomised partner;
• Sexual abstinence.

You may not qualify if:

• Positive test result for Quantiferon- TB Gold test, syphilis, hepatitis B, hepatitis C, or Human Immunodeficiency Virus (HIV)-1 or 2.
• Vaccination with live vaccines within 3 months prior to Screening or intention to receive live vaccines during the trial or up to 3 months after the administration of the study drug. Non-live vaccines should be administered at least a week before the study drug administration to avoid interference with vaccine immunity development (and to get clean readout of test drug related immunogenicity development).
• Any prior exposure to abatacept or to any other agent directly acting on CTLA4 or the CD28-CD80 co-stimulation pathway \[eg. pembrolizumab (Keytruda), ipilimumab (Yervoy), nivolumab (Opdivo) and atezolizumab (Tecentriq)\] including investigational products (to prevent interaction and resultant safety concerns).
• History of Immunodeficiency or other clinically significant immunological disorders, or auto-immune disorders.
• History of systemic fungal infection for the last 6 months.
• Subject with ongoing or frequent/ recurring infection (defined as more than 3 infections requiring treatment per year) or prior herpes zoster infection not fully healed (including the post-herpetic neuralgia period if occurring) within 1 year prior to randomisation.
• Allergy or hypersensitivity to any recombinant human or humanized antibodies, other therapeutic proteins or any excipients (dibasic sodium phosphate anhydrous, monobasic sodium phosphate monohydrate, L-Histidine, sodium chloride, poloxamer and sucrose) in the study formulations.
• History and/or current presence of clinically significant (in the opinion of the Investigator) atopic allergy (e.g., asthma including childhood asthma, urticaria, angioedema, eczematous dermatitis), hypersensitivity or allergic reactions or any history or presence of vasculitis or psoriasis.
• Non-suitable skin at planned injection site for dosing or changes in the injection site interfering with its evaluation, including presence of tattoos, pigmentation or lesions obscuring the injection site.
• Blood donation, participation in any study requiring repeated blood sampling or haemorrhage requiring treatment or any transfusion in the past 3 months or Plasma donation within the 14 days prior to screening.
• Screening blood pressure higher than 140 mm Hg (systolic) or higher than 90 mm Hg (diastolic) or volunteers currently on antihypertensive drugs. Higher values are allowed at baseline (at Day -1 and/or Day 1) if considered as clinically not relevant at the discretion of Investigator. At screening, blood pressure assessment up to 2 repeats in different days (2 repeats on the same day are also allowed if white coat hypertension is suspected) are allowed and, in this case, the mean of the measurements will be used to decide on eligibility. Blood pressure is to be measured on the same arm in the sitting position after 5 minutes' rest.
• History of relevant (in the Opinion of the Investigator) orthostatic hypotension, fainting spells, or blackouts as well as history of difficulties with blood sampling which potentially may interfere with the study objectives, as per the opinion of the Investigator.
• QTc (Fridericia correction) longer than 450 milliseconds or other clinically relevant ECG abnormalities such as atrial fibrillation, atrial flutter, Wolf-Parkinson-White syndrome, presence of a cardiac pacemaker or other abnormalities that are clinically relevant as per investigator assessment.
• History or presence of any clinically relevant nervous system disease including, but not restricted to any stroke/ transient ischaemic attack or of seizures (other than history of febrile seizures before the age of 5 years, which now have subsided).
• History of and/or current cardiovascular (including history of or presence of angina, exertional dyspnea, orthopnea, congestive heart failure or myocardial infarction and thrombotic or embolic episode requiring treatment), hematological (including pancytopenia, aplastic anemia or blood dyscrasia and coagulopathies or an International Normalized Ratio \[INR\] higher than 1.5), neurological, pulmonary (including chronic obstructive pulmonary disease), gastrointestinal, hepatic, renal, endocrine, metabolic (including known diabetes mellitus) disorder or condition. This criterion includes any disorder or condition that, in the investigator's opinion, may interfere with the safety of the subject, the study evaluations or the subject compliance to the study procedures and limitations.

Sponsors & Collaborators

• Dr. Reddy's Laboratories Limited: lead

Study Sites (3)

ICON, plc.

Lenexa, Kansas, 66219, United States

RECRUITING

ICON Early Phase Services, LLC

San Antonio, Texas, 78209, United States

RECRUITING

ICON

Salt Lake City, Utah, 84124, United States

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Naveen Reddy, MD

  Dr. Reddy's Laboratories

  STUDY CHAIR

Central Study Contacts

Vinu Jose, MD DM

CONTACT

+91 - 40-4464-4000; vinujosem@drreddys.com

Dharma Rao Uppada, MD DM

CONTACT

+91 - 40-4464-4000; Dharmaraou@drreddys.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2023
• First Posted: November 13, 2023
• Study Start: October 3, 2023
• Primary Completion: April 1, 2024
• Study Completion: July 1, 2024
• Last Updated: November 13, 2023

Record last verified: 2023-11

Locations

US (3)