Healthy volunteers Other
Conditions
Interventions
This was a Phase 1, first-in-human, randomised, double-blind study to evaluate the safety, tolerability, PK, pharmacodynamics (PD) and immunogenicity of different dose levels of GS-0272, a monoclonal
however, Part B was considered optional and following discussions with the study Sponsor, it was determined that the conduct of Part B was not required. The study enrolled 80 participants in Part A an
Sponsors
Gilead Sciences (United States)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Healthy males and female participants, between =18 and =65 years of age, inclusive. 2. Female participant of non-childbearing potential. For the purposes of this study, this is defined as the participant being amenorrhoeic for at least 12 consecutive months or at least 4 months post-surgical sterilisation (including bilateral oophorectomy with or without hysterectomy). 3. Female participant with a negative pregnancy test at screening. 4. Female participant of menopausal status as defined by no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level falls within the respective postmenopausal pathology reference range may be used to confirm a postmenopausal state in females not using hormonal contraception or hormonal replacement therapy. A single FSH measurement is insufficient in the absence of 12 months of amenorrhea. 5. Participants assigned male at birth (and partner of childbearing potential) willing to use a highly effective method of contraception or 2 effective methods of contraception, if applicable (unless anatomically sterile or where abstaining from heterosexual intercourse is in line with the preferred and usual lifestyle of the participant) from first dose until 3 months after last dose of IMP. 6. Participant with a body mass index (BMI) of 18-30 kg/m². BMI = body weight (kg) /[height (m)]². 7. No clinically significant history of previous allergy / sensitivity to GS-0272 or any of the excipients contained within the IMP. 8. No clinically significant abnormal test results for serum biochemistry, haematology and/or urine analyses within 28 days before the first dose administration of the IMP. 9. Participant with a negative urinary drugs of abuse (DOA) screen (including alcohol) test results, determined within 28 days before the first dose administration of the IMP (N.B.: A positive test result may be repeated at the Investigator’s discretion). 10. Participant with negative human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCV Ab) test results at screening. 11. No clinically significant abnormalities in 12-Lead electrocardiogram (ECG) (e.g. a PR interval = 220 ms, QRS width = 120 ms, QT interval corrected using Fredericia’s formula QTcF = 450 ms) determined within 28 days before first dose of IMP. 12. No clinically significant abnormalities in vital signs (e.g., blood pressure, systolic blood pressure = 140 mmHg, diastolic blood pressure = 90 mmHg, heart rate = 40 or = 100 bpm, oral temperature) determined within 28 days before first dose of IMP. 13. Participant must be available to complete the study (including all follow-up visits). 14. Participant must satisfy an Investigator about his/her fitness to participate in the study. 15. Participant must provide written informed consent to participate in the study. 16. Participants with a negative COVID-19 test on admission (if required).
Exclusion criteria
Exclusion criteria: 1. Presence of any significant acute or chronic, uncontrolled medical/ psychiatric illness. 2. History or evidence of clinically relevant immunological disorders, or other autoimmune disease, or known immunodeficiency of any cause (e.g., rheumatoid arthritis, lupus erythematosus, scleroderma, etc). 3. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 28 days or 5 half-lives (whichever is longer) prior to the first dose of IMP. 4. Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction. 5. A clinically significant history of drug or alcohol abuse (defined as the consumption of more than 14 units [for male and female participants] of alcohol a week) within the past two years. 6. Inability to communicate well with the Investigators (i.e., language problem, poor mental development or impaired cerebral function). 7. Participation in a New Molecular Entity (NME) clinical study within the previous 3 months or five half-lives, whichever is longer, or a marketed drug clinical study within the 30 days or five half-lives, whichever is longer, before the first dose of IMP. (Washout period between studies is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study). 8. Receipt of immunoglobulin or other blood products within 3 months prior to screening. 9. Receipt of a vaccine within 60 days prior to screening. 10. Receipt of any systemic immunosuppressant agent, antibody or biologic medicinal product within 6 months prior to screening. 11. Receipt of any systemic steroid within 2 months prior to screening. 12. Donation of 450 mL or more blood within the 3 months before the first dose of IMP. 13. History of allergic disease or reactions likely to be exacerbated by any component of GS-0272. 14. Malignancy within 5 years prior to screening with the exception of specific cancers that are cured by surgical resection (e.g. except basal cell skin carcinoma of the skin and cervical carcinoma). Participants under evaluation for possible malignancy are not eligible. 15. Significant cardiac disease or unstable uncontrolled cardiac disease. 16. Any other finding that, in the opinion of the Investigator, deems the participant unsuitable for the study. 17. Vegans, vegetarians or other dietary restrictions (e.g., restrictions for medical, religious or cultural reasons, etc). 18. Users of nicotine products i.e., current smokers or users of cigarette replacements (i.e., ecigarettes, nicotine patches or gums) with consistent use of > 5 cigarettes/replacements per day. 19. Female participants who are pregnant, breastfeeding or lactating.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Adverse Events are recorded from the point of informed consent up to final post-study follow up visit in each part 2. Laboratory safety (biochemistry, haematology, coagulation and urinalysis) is measured at set timepoints from screening through to post-study follow up visit (Day 85) 3. Vital signs (systolic/diastolic blood pressure, heart rate, oral body temperature) are measured at set timepoints from screening through to post-study follow up visit (Day 85) 4. 12 lead ECG (heart rate, RR interval, PR interval, QRS duration, QT interval, QTcF interval) is measured at set timepoints from screening through to post-study follow up visit (Day 85) 5. Infusion/Injection Site Reaction is measured at set timepoints from screening through to post-study follow up visit (Day 85) | — |
Secondary
| Measure | Time frame |
|---|---|
| Measured using plasma concentration analysis at set timepoints from screening through to post-study follow up visit (Day 85): 1. Cmax 2. Tmax 3. ?z 4. t1/2 5. AUC0-tlast 6. AUC0-inf 7. AUC%extrapolated 8. Total body clearance (CL) 9. Vz 10. CL/F (SC administration only) 11. Vz/F (SC administration only) | — |
Countries
United Kingdom, Wales
Contacts
Public ContactKanika Chhabra
Outcome results
None listed