CTRI/2024/05/067154 [Registered on: 10/05/2024] Trial Registered Prospectively
Last Modified On:
29/10/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Biological
Study Design
Randomized, Parallel Group Trial
Public Title of Study
A comparative study with Abatacept products in healthy male volunteers
Scientific Title of Study
A Single Dose, Double-Blind, Parallel Arm, Comparative Pharmacokinetic Study of DRL_AB, US licensed Reference Abatacept (Orencia®) and EU approved Reference (Orencia®), Administered by the Subcutaneous Route to Male Normal Healthy Volunteers.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
AB-01-001 V.05 dated 13 Oct 2023
Protocol Number
NCT06126042
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Bharath N
Designation
Principal Investigator
Affiliation
Human Pharmacology Unit, Syngene International Ltd
Address
Syngene International Limited, Clinical Development, Tower I, Semicon Park, Electronic City, Phase- II, Hosur Road
Bangalore KARNATAKA 560100 India
Phone
9900906630
Fax
Email
Bharath.N101@syngeneintl.com
Details of Contact Person Scientific Query
Name
Narendra Maharaj
Designation
Head - Clinical Development
Affiliation
Dr. Reddys Laboratories Ltd
Address
Dr. Reddys Laboratories Ltd.
Biologics
Survey No.47 and 44(PART), Bachupally Village,
Bachupally Mandal,
Medchal Malkajgiri District,
Medchal TELANGANA 500090 India
Phone
04044644000
Fax
04023041418
Email
narendramaharaj@drreddys.com
Details of Contact Person Public Query
Name
Naveen Reddy
Designation
Head - Insourced Clinical Operations
Affiliation
Dr. Reddys Laboratories Ltd
Address
Dr. Reddys Laboratories Ltd.
Biologics
Survey No.47 and 44(PART), Bachupally Village,
Bachupally Mandal,
Medchal Malkajgiri District,
Medchal TELANGANA 500090 India
Phone
04044644000
Fax
04023041418
Email
naveenreddy@drreddys.com
Source of Monetary or Material Support
M/s Dr Reddys Laboratories Limited, 8-2-337, Road No. 3 Banjara Hills, Hyderabad (India) – 500034.
Primary Sponsor
Name
Dr. Reddys Laboratories Ltd.
Address
Biologics, Survey No. 47 and 44(Part), Bachupally Village, Bachupally Mandal,Medchal Malkajgiri District, Telangana, INDIA – 500 090
SRM Medical College Hospital and Research Centre, SRM Nagar, Potheri, Kattankulathur, Kancheepuram, Chennai Kanchipuram, Tamil Nadu- 603203
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Healthy Human Volunteers
Not applicable
Intervention / Comparator Agent
Type
Name
Details
Intervention
Dr Reddys Abatacept (DRL_AB)
Subjects will receive 1 dose of either treatment DRL_AB or RP or RMP as per the randomisation schedule. Single SC injection of 125 mg will be administered.
Comparator Agent
EU approved Reference (Orencia®)
Subjects will receive 1 dose of either treatment DRL_AB or RP or RMP as per the randomisation schedule. Single SC injection of 125 mg will be administered.
Comparator Agent
US licensed Reference Abatacept (Orencia®)
Subjects will receive 1 dose of either treatment DRL_AB or RP or RMP as per the randomisation schedule. Single SC injection of 125 mg will be administered.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
50.00 Year(s)
Gender
Male
Details
1. Healthy Male volunteers, 18 to 50 years of age (both age inclusive), at the time of signing informed consent.
2. 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.
3. 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 less than 80 kg and greater than or equal to 80.0 to 100.0 Kg).
4. Screening parameters (vital signs, physical examination, clinical laboratory tests, 12-lead ECG, thyroid function) within the normal range or if outside the normal range then assessed as clinically non-significant by the Investigator (unless the value constitutes an explicit exclusion criterion).
5. 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.
6. Capable, and amenable to providing written informed consent to the study requirements.
7. Willing to stay on study restrictions for up to 16 weeks (from the time of Screening until 3 months after dosing for contraception), and abide by the study procedures during the follow up if and as applicable.
ExclusionCriteria
Details
1. Positive test result for Quantiferon- TB Gold test, syphilis, hepatitis B, hepatitis C, or Human Immunodeficiency Virus (HIV)-1 or 2.
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).
3. 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).
4. History of Immunodeficiency or other clinically significant immunological disorders, or auto-immune disorders.
5. History of systemic fungal infection for the last 6 months.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. Screening blood pressure higher than 140 mm Hg (systolic) or higher than 90 mm Hg (diastolic) or volunteers currently on anti-hypertensive 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.
Note: At screening, blood pressure assessment up to 2 repeats in different days (2 repeats on the same day are also allowed if white coathypertension 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.
12. 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.
13. 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.
14. 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).
15. 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.
16. Impaired hepatic function (alanine transaminase [ALT] or aspartate transaminase [AST] value greater than 1.5 times the upper limit of the reference range and/or serum bilirubin 1.5 times the upper limit of the reference range at the screening visit). A single repeat in a different day is allowed. Subjects who have documented evidence of presence of Gilbert’sdisease may be included in the study if they have total bilirubin of less than 3 mg/dL (or less than 51.3 μmol/L) with indirect bilirubin contributing to greater than 80% of the total bilirubin as per the laboratory test.
17. Any active infection assessed by Investigator including Coronavirus disease of 2019 (COVID-19) infection, even if minor, ongoing at the time of Screening or dosing.
18. Participation in an interventional or Phase 1 study in the last 3 months, participation in more than 3 studies of experimental drug products in the past 12 months or intake of an investigational drug in another trial within 3 months or 5 t1/2 (whichever is longer with 6-months period required for experimental drugs with unknown t1/2) prior to intake of study drug in this trial or planned intake of another investigational drug during the course of this trial.
Some examples of drugs, as exceptions to these criteria with adequate washout period (either as an investigational product or for treatment) are provided for reference:
a. Medications which require longer washout:
10 weeks: Bismuth salts, digitoxin, fluoxetine, flurazepam,medazepam, mephenytoin, mephobarbital, phenprocoumone, phenylbutazone, pimozide, pirimethamine, phenobarbital, primidone, protryptiline, teicoplanin.
18 weeks: flunarizine, mefloquine, trimethadione.
26 weeks: gold salts, immunoglobulins (antitetanus and antirabies post-exposure prophylaxis allowed until 3 weeks predose) or antibodies (monoclonal or not) systemic retinoids, chloroquine, hydroxychloroquine and amiodarone.
Note: In case of USA located sites: Participants participating in an interventional or Phase 1 study in the last 30 days, participation in more than 4 studies of experimental drug products in the past 12 months or intake of an investigational drug in another trial within 30 days or 5 t1/2 of that drug (whichever is longer [6-months period required for experimental drugs with unknown t1/2]), prior to intake of the current study drug in this trial, or planned to take another investigational drug during the course of this trial will be excluded.19. History of any cancer, including carcinoma in situ, lymphoma or leukaemia.
20. Major surgery within the past 6 months, or any surgery including dental interventions planned within 3 months of study enrolment and during study period.
21. Current smokers or those who gave up smoking less than 3 months prior to screening, tobacco chewer or those who gave up tobacco chewing less than 3 months prior to screening, (thus 3 months cessation required at screening time), or positive in the urine cotinine test at screening or predose.
22. Positive test for ethanol in breath or in urine (following the site/ clinical facility standard) or drugs of abuse (benzodiazepine, amphetamines, barbiturates, cocaine, methadone, phencyclidine, 3, 4 methylenedioxymethamphetamine (ecstasy), tetrahydrocannabinol, and opiates) in urine at screening or at check-in/ admission to clinical facility.
Method of Generating Random Sequence
Stratified randomization
Method of Concealment
Not Applicable
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Pharmacokinetic parameters (calculated by standard non-compartmental methods on actual sampling times): AUC(0-∞) and Cmax.
Samples for PK analysis will be obtained within 1 hour prior to the administration of study drug, and at 1h, 4h, 12h, 24h, 36h, 48h (Day 3), 60h (Day 3), 72h (Day 4), 84h (Day 4), 96h (Day 5), 108h (Day 5), 120h (Day 6), 132h (Day 6), 144h (Day 7), 156h (Day 7), 168h (Day 8), 216 h (Day 10) and on days 15, 22, 29, 36, 43, 50, 57, 71 and 85 (EOS).
Secondary Outcome
Outcome
TimePoints
Pharmacokinetic parameters: AUC(0-t), tmax, apparent terminal decline rate constant λz (also known as apparent terminal elimination rate constant Kel), half-life (t1/2), CL/f, & Vz/f; %AUCext will be reported to evaluate the coverage of AUC by the sampling schedule but is not considered a PK endpoint.
Safety & tolerability of all treatments
Comparative incidence of anti-abatacept antibodies
A total of 5 blood samples for immunogenicity assessment will be collected; time points should be pre-dose, on days 15, 29, 43 & at the EOS (85 days) visit post-dose for all subjects.
Target Sample Size
Total Sample Size="330" Sample Size from India="140" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a Phase 1 comparative study conducted by Dr. Reddy’s Laboratories Ltd in male volunteers with DRL_AB vs. US licensed Reference Abatacept (Orencia®) and EU approved Reference (Orencia®) to compare the Pharmacokinetic parameters.
Dr.Reddy’s Abatacept (company product code: DRL_AB) is being developed as a biosimilar to the US licensed Reference Abatacept (Orencia®) and EU approved Reference (Orencia®) as a part of global development program.
Normal healthy volunteers (NHV) are the population of choice (unless precluded for safety reasons) to establish PK similarity. The current study will be performed only in male subjects to avert gender-related variability. The 125 mg SC single dose is known to be safe for administration to NHV as it has been tested with appropriate safety and tolerability in prior studies.