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
概览
- 阶段
- 1 期
- 干预措施
- Test Product
- 疾病 / 适应症
- Rheumatoid Arthritis
- 发起方
- Dr. Reddy's Laboratories Limited
- 入组人数
- 330
- 试验地点
- 3
- 主要终点
- Single-dose pharmacokinetic parameter Maximum observed serum concentration (Cmax) will be derived from serum concentration versus time data [Time frame over 85 days]
- 状态
- 招募中
- 最后更新
- 2年前
概览
简要总结
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.
详细描述
This will be a randomised, double-blind, single dose, parallel groups study to compare the PK, safety and immunogenicity of 3 abatacept products (DRL_AB, RP and RMP) in Male NHV. 330 subjects will be randomised 1:1:1 to receive a single 125 mg SC dose of abatacept administered as either DRL_AB or RP or RMP. A BSSR (blinded sample size re-estimation) will be performed when the data from approximately 132 NHV (44 per arm) is available. Study randomisation will be stratified by body weight (lower half of the allowed range and upper half of the allowed range i.e. 60.0 to \<80 kg and ≥80.0 to 100.0 Kg).
研究者
入排标准
入选标准
- •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).
- •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).
- •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;
排除标准
- •Positive test result for Quantiferon- TB Gold test, syphilis, hepatitis B, hepatitis C, or Human Immunodeficiency Virus (HIV)-1 or
- •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.
研究组 & 干预措施
DRL_AB
Drug: Abatacept Prefilled Syringe Each pre-filled syringe contains 125 mg of abatacept in 1 mL Other Name: Dr. Reddy's Abatacept
干预措施: Test Product
RP
Drug: Abatacept Prefilled Syringe Each pre-filled syringe contains 125 mg of abatacept in 1 mL Other Names: Orencia
干预措施: Reference product
RMP
Drug: Abatacept Prefilled Syringe Each pre-filled syringe contains 125 mg of abatacept in 1 mL Other Names: Orencia
干预措施: Reference Medicinal Product
结局指标
主要结局
Single-dose pharmacokinetic parameter Maximum observed serum concentration (Cmax) will be derived from serum concentration versus time data [Time frame over 85 days]
时间窗: 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)
Pharmacokinetic parameters - Cmax
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]
时间窗: 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)
Pharmacokinetic parameters - AUC (0-∞)
次要结局
- Change from baseline in body temperature(At screening and 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))
- Number of participants with abnormal well being assessment.(At screening and Day 85 (End Of Study))
- Vz/f(1hour prior to the drug administration till Day 85 (End Of Study))
- %AUCext(1hour prior to the drug administration till Day 85 (End Of Study))
- Number of Participants With Positive Abatacept-induced Immunogenicity Response(pre-dose and Day 85 (End Of Study))
- Change from baseline measurement of respiratory rate in breaths/ minute(At screening and Day 85 (End Of Study))
- Number of Participants With Adverse Events (AEs)(At screening and Day 85 (End Of Study))
- 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))
- t1/2(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))
- CL/f(1hour prior to the drug administration till Day 85 (End Of Study))
- Change From Baseline in Systolic and diastolic Blood Pressure(At screening and Day 85 (End Of Study))
- Change from baseline measurement of pulse rate in beats/ minute(At screening and Day 85 (End Of Study))
- Number of participants with abnormal physical examination(Day -1 (before to dosing), Day 5 and End of study)
- Number of Participants with abnormally marked hematology laboratory parameters.(At screening and Day 85 (End Of Study))
- Number of Participants with abnormally marked Serum Chemistry laboratory parameters.(At screening and Day 85 (End Of Study))
- Number of Participants with abnormally marked urinalysis laboratory parameters(At screening and Day 85 (End Of Study))
- Number of participants with post dose ECG parameters reported as an Adverse event(At screening and Day 85 (End Of Study))
- Number of participants with injection site reactions reported as an Adverse event.(At screening and Day 85 (End Of Study))