A comparative study with Abatacept products in healthy male volunteers
- Registration Number
- CTRI/2024/05/067154
- Lead Sponsor
- Dr. Reddys Laboratories Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
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.
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 syndr
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Pharmacokinetic parameters (calculated by standard non-compartmental methods on actual sampling times): AUC(0-8) and Cmax.Timepoint: 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 Measures
Name Time Method Pharmacokinetic parameters: AUC(0-t), tmax, apparent terminal decline rate constant ?z (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. <br/ ><br> Safety & tolerability of all treatments <br/ ><br> Comparative incidence of anti-abatacept antibodiesTimepoint: 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.