Healthy Participants
Conditions
Keywords
Pharmacokinetics
Brief summary
This phase 1 study compared the pharmacokinetics of a single intravenous dose of SHR-8068 injection with ipilimumab (YERVOY®) in healthy Chinese men. Safety and immunogenicity were also evaluated.
Detailed description
The study comprised an open-label pilot stage and a double-blind formal stage. In the pilot stage, 12 healthy Chinese men were randomized in parallel to receive a single 0.3 mg/kg intravenous infusion of SHR-8068 (n=6) or ipilimumab (n=6). The pilot evaluated safety, pharmacokinetic characteristics and variability, and immunogenicity, and informed optimization of pharmacokinetic and immunogenicity sampling for the formal stage. In the formal stage, 112 healthy Chinese men were randomized in a 1:1 ratio, under double-blind conditions, to receive a single 0.3 mg/kg intravenous infusion of SHR-8068 (n=56) or ipilimumab (n=56) in a single-period, parallel design. The primary pharmacokinetic parameters were maximum serum concentration (Cmax) and area under the serum concentration-time curve from time zero extrapolated to infinity (AUC0-inf). Other pharmacokinetic parameters, safety, and immunogenicity were also evaluated. Formal-stage pharmacokinetic equivalence was assessed using the 90% confidence intervals for the geometric mean ratios of Cmax and AUC0-inf, with prespecified limits of 80.00% to 125.00%.
Interventions
BIOLOGICALSHR-8068
SHR-8068 injection, 0.3 mg/kg, administered once by intravenous infusion over 30 ± 10 minutes.
BIOLOGICALIpilimumab
Ipilimumab injection (YERVOY®), 0.3 mg/kg, administered once by intravenous infusion over 30 ± 10 minutes.
Sponsors
The Affiliated Hospital of Qingdao University
Suzhou Suncadia Biopharmaceuticals Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The pilot stage was open-label. In the formal stage, participants, investigators, outcome evaluators, data management personnel, and statisticians remained blinded; designated unblinded staff prepared study treatment when required.
Intervention model description
The study had two stages with the same two parallel intervention groups: an open-label pilot stage (12 participants) followed by a double-blind formal stage (112 participants).
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Provides written informed consent and is willing and able to comply with all protocol requirements. * Healthy male, 18 to 45 years of age, inclusive, on the date of informed consent. * Body weight 50 to 80 kg, inclusive, and body mass index 19.0 to 26.0 kg/m², inclusive. * Has no reproductive plans during the study and for 3 months after the last dose; agrees to use effective contraception and not donate sperm during this period.
Exclusion criteria
* History of autoimmune disease. * History of malignancy, except successfully resected cutaneous squamous cell carcinoma, basal cell carcinoma, or localized cervical carcinoma in situ without evidence of metastasis. * Positive test for human immunodeficiency virus antibody, hepatitis B surface antigen, hepatitis B e antigen, hepatitis C virus antibody, or Treponema pallidum antibody. * Known history of recurrent or chronic infection, including but not limited to chronic renal infection, chronic chest infection such as bronchiectasis, sinusitis, recurrent urinary tract infection, or an open, draining, or infected skin wound. * Acute infection within 2 weeks before screening. * Opportunistic infection within 6 months before screening, including herpes zoster or active cytomegalovirus, Pneumocystis, Histoplasma, Aspergillus, or mycobacterial infection. * Known history of tuberculosis, clinical findings suspicious for tuberculosis, or a positive tuberculosis laboratory test. * History of chronic or serious disease, or current disease, involving the respiratory, cardiovascular, digestive, urinary, hematologic, endocrine, immune, neurologic, or psychiatric systems, or otherwise considered unsuitable by the investigator. * Allergic constitution, including a history of severe drug allergy or hypersensitivity, a definite allergy history, or allergy to either study drug or its components; untreated asymptomatic seasonal allergy or an isolated positive skin test is not exclusionary. * Any surgery within 6 months before screening or planned surgery during the study. * Blood loss or donation of at least 400 mL within 3 months before screening, or at least 200 mL within 1 month before screening, or receipt of a blood transfusion within 3 months before screening. * Clinically significant abnormality in physical examination, vital signs, laboratory tests, 12-lead electrocardiogram, abdominal ultrasonography, or chest radiography during screening. * History of illicit drug use or drug abuse within 1 year before screening, or a positive drug screen. * Habitual alcohol or tobacco use (an average of at least 14 units of alcohol per week within 6 months before screening, where 1 unit equals 285 mL beer, 25 mL spirits, or 100 mL wine; or an average of at least 5 cigarettes per day) and inability to abstain during the study. * Previous use of ipilimumab or an ipilimumab biosimilar. * Use of any medication within 2 weeks before the first study dose or within 5 half-lives of the medication, whichever is longer, or planned use of other medication during the study, including prescription or nonprescription drugs, Chinese herbal medicines, and dietary supplements. * Participation in a drug or medical-device clinical trial within 3 months before screening, ongoing follow-up in another clinical study, or exposure within 5 half-lives of the prior investigational drug, whichever is longer. * Receipt of a live vaccine within 6 months before screening or planned receipt of a live vaccine during the study. * History of needle or blood phobia, difficult blood collection, or inability to tolerate venipuncture. * Any other factor considered by the investigator to make participation unsuitable, or withdrawal for the participant's own reasons.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Serum Concentration (Cmax) | From start of infusion through 1344 hours (Day 57) after dosing | Cmax of SHR-8068 and ipilimumab in the formal study. Pharmacokinetic equivalence was assessed using the 90% confidence interval for the geometric mean ratio (SHR-8068/ipilimumab), with prespecified limits of 80.00% to 125.00%. |
| Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) | From start of infusion through 1344 hours (Day 57) after dosing | AUC0-inf of SHR-8068 and ipilimumab in the formal study. Pharmacokinetic equivalence was assessed using the 90% confidence interval for the geometric mean ratio (SHR-8068/ipilimumab), with prespecified limits of 80.00% to 125.00%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Serum Concentration-Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) | From start of infusion through 1344 hours (Day 57) after dosing | AUC0-t of SHR-8068 and ipilimumab in the formal study. |
| Number of Participants With Adverse Events and Serious Adverse Events | From dosing through Day 78 | Incidence and severity of adverse events and serious adverse events after a single intravenous dose of SHR-8068 or ipilimumab. |
| Number of Participants With Anti-Drug Antibodies | Predose and Days 15, 36, and 57 after dosing | Anti-drug antibodies against SHR-8068 or ipilimumab were assessed in serum. |
| Time to Maximum Serum Concentration (Tmax) | From start of infusion through 1344 hours (Day 57) after dosing | Tmax of SHR-8068 and ipilimumab in the formal study. |
| Terminal Elimination Half-Life (t1/2) | From start of infusion through 1344 hours (Day 57) after dosing | Terminal elimination half-life (t1/2) of SHR-8068 and ipilimumab in the formal study. |
| Clearance (CL) | From start of infusion through 1344 hours (Day 57) after dosing | Clearance (CL) of SHR-8068 and ipilimumab in the formal study. |
| Volume of Distribution at Steady State (Vss) | From start of infusion through 1344 hours (Day 57) after dosing | Volume of distribution at steady state (Vss) of SHR-8068 and ipilimumab in the formal study. |
Countries
China
Outcome results
None listed