OB-002H Gel Administered Vaginally and Rectally in HIV-1 Seronegative Adults

Study Overview
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Brief Summary
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This is a monocentric phase I study in open-label and randomized, double-blind, placebo-controlled cohorts of HIV-1 seronegative adults to evaluate the safety, acceptability, and pharmacokinetic of OB-002H Gel administrated vaginally and rectally.

Official Title
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A Monocentric Phase I Safety, Acceptability, and Pharmacokinetic Trial of OB-002H Gel Administered Vaginally and Rectally in Open-Label and Randomised, Double- Blind, Placebo-Controlled Cohorts of HIV-1 Seronegative Adults

Conditions
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HIV Prevention

Intervention / Treatment
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* Drug: OB-002
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 45 years (inclusive). HIV-1 antibody negative as documented at screening. Understands and agrees to local sexually transmitted infection (STI) reporting requirements. Able and willing to provide written informed consent to take part in the trial. Willing and able to return for a follow-up visit one week after last IMP administration, barring unforeseen circumstances. Of good general health in the opinion of the investigator. Willing to be sexually abstinent (anal and vaginal sex) for 72 hours before and after each visit except Visit 1. No participation in other clinical trials within the last three months prior Visit 1 and throughout the trial. Willing to abstain from inserting any non-trial products for rectal or vaginal application for 72 hours prior to each trial visit. For female participants only: Using (or willing to use) highly effective (i.e. failure rate <1% per year) methods of contraception for the duration of trial participation. Such methods include combined oral or transdermal hormonal contraception associated with inhibition of ovulation, oral, injectable or implantable progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device [IUD] or intrauterine hormone-releasing system [IUS] inserted at least 28 days prior to the Screening Visit, bilateral tubal occlusion, surgical sterilization, successful vasectomisation of male partner or sexually abstinent for the past 90 days and during the trial. If the female participant has female partners only, the method of contraception will be noted as abstinence to heterosexual activities in the trial documentation. Not pregnant at the screening. Not breastfeeding at screening nor intending to breastfeed during trial participation per participant report. In addition, participants enrolled in the corresponding cohorts must meet the following criteria: Cohorts A1 and B1 only: Willing to stay at the site overnight for two nights. Cohort A2 only: Willing to stay at the site overnight for six nights. Cohort A3 only: Willing to stay at the site overnight from Day 1 to Day 2 and from Day 5 to Day 6 for PK blood sampling. Exclusion Criteria: Following laboratory findings at screening: Haemoglobin < 10.0 g/dL Platelet count < 100 000/mm3 White blood cell count < 2 000 cells/mm3 or > 15 000 cells/mm3 Glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 Alanine transaminase (ALT) and/or aspartate aminotransferase (AST) > 2.5× laboratory upper limit of normal (ULN) Abnormal glucose or protein on urinalysis (UA) Known allergy or intolerance to any of the IMP excipients (sodium sorbate, sodium chloride, acetic acid, natrasol). By participant report at screening: Use of post-exposure prophylaxis (PEP) for HIV exposure, systemic immunomodulatory medications vaginally or rectally administered medications, and vaginally or rectally administered products (including condoms) containing nonoxynol-9 (N-9) within the last four weeks prior to Visit 1. Any significant underlying medical condition or prior therapy that, in the opinion of the investigator, would preclude informed consent, make trial participation unsafe, make the individual unsuitable for the trial or unable to comply with the trial requirements. Such conditions may include, but are not limited to, current or recent history of severe, progressive, or uncontrolled renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, neurological, cardiovascular, immunological or cerebral disease. Abnormalities of the cervical (females only), vaginal (females only), or colorectal mucosa, or significant symptom(s), which in the opinion of the clinician represents a contraindication to protocol-required biopsies (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, and presence of symptomatic external haemorrhoids). Suspected or confirmed drug or alcohol abuse. Positive hepatitis B virus (HBV) or hepatitis C virus (HCV) test results. HSV-1 or HSV-2 seropositive diagnosis will only be allowed if no active lesions are present and since treatment is not required. Body mass index (BMI) < 18 or > 30 kg/m2. Previous enrolment to any preceding cohort of this trial. Persons committed to an institution by virtue of an order issued either by the judicial or other authorities. In addition to the criteria listed above, female participants will be excluded if they meet any of the following criteria: Last pregnancy outcome or gynaecological surgery within 90 days prior to screening Chronic and/or recurrent symptomatic vaginal candidiasis at screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single dose administration (Part 1)<br>the dose of the drug (4g OB-002H (8.0 mg/g)) administrated once vaginally or rectally | Drug: OB-002<br>* vaginal or rectal administration<br>|
| Experimental: Multidose administration (Part 2)<br>the dose of the drug (4g OB-002H (8.0 mg/g)) or placebo administered vaginally through five consecutive days | Drug: OB-002<br>* vaginal or rectal administration<br>Drug: Placebo<br>* vaginal or rectal administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety of OB-002H gel after single- and multiple-dose application based on the number of observed AEs | For the primary safety analysis, the number of ≥ Grade 2 AEs, as well as the number and the percentage of participants with corresponding AEs, will be tabulated overall and per cohort, by system organ class (SOC) and by preferred term (PT). Additional AE analyses will also tabulate the number of AEs ≥ Grade 2 observed overall, by relationship and by severity. AEs ≥ Grade 2 that lead to discontinuation of trial participation will be tabulated separately. The safety set will be used for the primary safety analysis. | approximately 5 weeks for single dose and approximately five to seven weeks for multi-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acceptability | Participants will receive a placebo sample to check and evaluate the OB-002H gel and will be asked to answer the questions in the questionnaire with Likert scale | assessment done on the visit conducted 24 hours after IMP administration | 
| OB-002 serum concentration at different time points for the calculation of PK parameters (area under the concentration-time curve (AUC). | In each Part of the trial, the parameters will be summarised descriptively by cohort and treatment arm (Part 2 only: OB-002H and placebo). | Serum samples collected within 24 hours after dosing | 
| OB-002 serum concentration at different time points for the calculation of PK parameters (maximum concentration (Cmax). | In each Part of the trial, the parameters will be summarised descriptively by cohort and treatment arm (Part 2 only: OB-002H and placebo). | Serum samples collected within 24 hours after dosing | 
| OB-002 serum concentration at different time points for the calculation of PK parameters (time to maximum concentration (tmax). | In each Part of the trial, the parameters will be summarised descriptively by cohort and treatment arm (Part 2 only: OB-002H and placebo). | Serum samples collected within 24 hours after dosing | 
| OB-002 serum concentration at different time points for the calculation of PK parameters (minimum concentration (Cmin). | In each Part of the trial, the parameters will be summarised descriptively by cohort and treatment arm (Part 2 only: OB-002H and placebo). | Serum samples collected within 24 hours after dosing | 
| OB-002 serum concentration at different time points for the calculation of PK parameters (concentration half-life (t½). | In each Part of the trial, the parameters will be summarised descriptively by cohort and treatment arm (Part 2 only: OB-002H and placebo). | Serum samples collected within 24 hours after dosing |