None listed
Conditions
Brief summary
This is a Phase 1, multi-centre, international, open-label study to evaluate the safety, tolerability, and pharmacokinetics of subcutaneously and intramuscularly administrated Lenacapavir in healthy participants. This study aims at further finding the drug concentration and dose required to support taking Lenacapavir monthly to twice-yearly, for use in the prevention of HIV-1 infection
Interventions
Every participant will be receiving a single dose of either SC or IM administered Lenacapavir and the formulations and dose level of Lenacapavir will vary between cohorts with or without an Optional 600 mg loading oral dose of Lenacapavir and/ or optional pretreatment/coadministration of up to 600 units/injection recombinant human hyaluronidase on Day 1 and Day 2 based on emerging data from previous cohorts.
Cohort 1 will receive a dose of 1200 mg SC LEN on Day 1
Cohort 2 will receive a dose of
Every participant will be receiving a single dose of either SC or IM administered Lenacapavir and the formulations and dose level of Lenacapavir will vary between cohorts with or without an Optional 600 mg loading oral dose of Lenacapavir and/ or optional pretreatment/coadministration of up to 600 units/injection recombinant human hyaluronidase on Day 1 and Day 2 based on emerging data from previous cohorts. Cohort 1 will receive a dose of 1200 mg SC LEN on Day 1 Cohort 2 will receive a dose of up to 1200 mg SC LEN on Day 1, with an optional tablet loading oral dosage of 600 mg of LEN on Day 1 and Day 2 Cohort 3 will receive a dose of up to 1200 mg SC LEN on Day 1 Cohort 4 will receive a dose of 100 mg SC LEN on Day 1 Cohort 5 will receive a dose of up to 300 mg SC LEN on Day 1, with an optional tablet loading oral dosage of 600 mg of LEN on Day 1 and Day 2 Cohort 6 will receive a dose of up to 800 mg SC LEN on Day 1, with an optional tablet loading oral dosage of 600 mg of LEN on Day 1 and Day 2 Cohort 7 will receive a dose of 125 mg SC LEN on Day 1 Cohort 8 will receive a dose of up to 375 mg SC LEN on Day 1, with an optional tablet loading oral dosage of 600 mg of LEN on Day 1 and Day 2 Cohort 9 will receive a dose of up to 1000 mg SC LEN on Day 1, with an optional tablet loading oral dosage of 600 mg of LEN on Day 1 and Day 2 Cohort 10 will receive a dose of 150 mg SC LEN on Day 1 Cohort 11 will receive a dose of up to 450 mg SC LEN on Day 1, with an optional tablet loading oral dosage of 600 mg of LEN on Day 1 and Day 2 Cohort 12 will receive a dose of up to 1200 mg SC LEN on Day 1, with an optional tablet loading oral dosage of 600 mg of LEN on Day 1 and Day 2 Cohort 13 will receive an oral tablet loading dose of 600 mg LEN with up to 600 mg SC LEN on Day 1. And oral tablet loading dose of 600 mg LEN ill be given on Day 2 Cohort 14 and 15 will receive up to 5000 mg IM LEN on Day 1, with an optional tablet loading oral dosage of 600 mg of LEN on Day 1 and Day 2 Cohorts 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38 and 39 will receive up to 5000 mg SC or IM LEN, with an optional tablet loading oral dosage of 600 mg of LEN and/ or optional pretreatment/coadministration of up to 600 units/injection recombinant human hyaluronidase on Day 1 and Day 2 The mode of administered to participants will be based on sponsor decision based on emerging data from previous cohorts. For the optional loading dose, the oral dosing of LEN tablet is sponsor decision based on emerging data from previous cohorts. For the optional pretreatment/coadministration of recombinant human hyaluronidase, the dosing of units/ injection is sponsor decision based on emerging data from previous cohorts. Strategies used to monitor adherence to the intervention if applicable is, all doses are administered by clinic by research nurse.
Sponsors
Gilead Sciences
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Be at aged 18 at screening. Be a nonsmoker. The use of nicotine-containing products must be discontinued 42 days prior to the administration of study drug. Have a creatinine clearance (CLcr) at least 90 mL/min (using the Cockcroft-Gault method {Cockcroft 1976}) based on serum creatinine and actual body weight, as measured at screening, Men and women of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception. Participants have not donated blood within 56 days of study entry or plasma within 7 days of study entry and must refrain from blood donation from clinic admission, throughout the study confinement period, and continuing for at least 253 days following the administration of study drug. Screening laboratory evaluations and 12-lead ECG evaluations must be without clinically significant abnormalities as assessed by the investigator. Have liver biometric tests of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin below or equal to 2.5 x the upper limit of normal at screening, (Grade 1 or below). Must be willing and able to comply with all study requirements. Must, in the opinion of the investigator, be in good health based upon medical history and physical examination, including vital signs.
Exclusion criteria
Positive serum or urine pregnancy test Breastfeeding woman. Is currently participating in or has participated in an interventional clinical study with an investigational medicinal product administered within 30 days prior to study dosing on Day 1 through the duration of the study. Has a tattoo or other dermatological condition overlying the injection site which in the opinion of the investigator, may interfere with interpretation of ISRs. Have current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance or participant safety, or a positive drug or alcohol test at screening or baseline. Have a positive test result for HIV at screening (antigen/antibody test) or Day -1 (rapid test). Have a positive test result for hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody at screening. Assessed by the investigator as being at risk for HIV infection in the past 6 months. This may include, but not limited to, one or more of the following risk factors: (a) unprotected vaginal or anal sex with a person with HIV; (b) sex work for money or drugs; (c) sexually transmitted infection; (d) injection of nonprescribed drugs for recreational use; (e) post- or pre-exposure prophylaxis (PEP or PrEP). Have poor venous access that limits phlebotomy. Have taken any prescription medications or over-the-counter medications, including herbal products, within 28 days prior to start of study drug dosing, with the exception of vitamins and/or acetaminophen and/or ibuprofen and/or hormonal contraceptive medications. Have been treated with systemic steroids, immunosuppressant therapies, or chemotherapeutic agents within 3 months prior to screening or is expected to receive these agents during the study. Have a history of: Significant serious skin disease, Significant drug sensitivity or drug allergy, Known hypersensitivity to the study drugs, their metabolites, or to formulation excipients, Significant cardiac disease, Syncope, palpitations, or unexplained dizziness. Implanted defibrillator or pacemaker. Liver disease, including Gilbert syndrome. Severe peptic ulcer disease, gastroesophageal reflux disease, or other gastric acid hypersecretory conditions requiring prolonged (> 6 months) medical treatment. Have any serious or active medical or psychiatric illness (including depression) that, in the opinion of the investigator, would interfere with participant treatment, assessment, or compliance with the protocol.
Outcome results
None listed