None listed
Conditions
Brief summary
Antiva is developing ABI-2280, a potent human DNA polymerase inhibitor, for topical treatment of several precancerous conditions related to human papillomavirus (HPV) infection, including high grade squamous intraepithelial lesions (HSIL) of the cervix. The purpose of this study is to assess the safety, tolerability and PK of ABI-2280 Vaginal Gel and Tablet, applied to the cervix of healthy female participants. The study will be conducted in two parts: Part A (Single Ascending Dose) and Part B (Multiple Ascending Dose). Part A There will be 4 Cohorts in this part, A1 -A4, each consisting of 8 participants. 6 participants will receive a single dose of ABI-2280 and 2 will receive a single dose of placebo. No participant will be enrolled in more than one cohort. Participants will be screened up to 49 days prior to dose administration. Participants may be admitted to research unit on Day -1 or morning of Day 1 and remain admitted until Day 2. On Day 1 participants will receive a single dose of ABI-2280 Vaginal Gel or Tablet or placebo. They will return to the clinic on Day 4 for safety follow up visit and Day 8 for end of study visit. Part B Up to approximately 16 participants will be enrolled into two cohorts- B1 and B2. Each cohort will consist of 8 participants (6 to receive ABI-2280 Vaginal Gel or Tablet and 2 to receive placebo). Participants will be screened up to 49 days prior to Day 1 dose administration. For cohorts B1 and B2, participants may be admitted to the research unit on Days -1 and 4 and discharged on Days 2 & 6 or if feasible, may be admitted through Day -1 to Day 5 and discharged on Day 6. On Days 1 & 5, they will receive the first and last doses of ABI-2280 Vaginal Gel or Tablet or placebo. Participants will have safety assessments and ABI-2280 or placebo administration on Days 3, safety follow-up visit on Day 9, and the End of Study (EOS) visit on Day 15.
Interventions
This is a randomized, double-blind, placebo-controlled, single and multiple dose
escalation first-in-human study in healthy female participants. The study is designed to assess the safety, tolerability and PK of ABI-2280 Vaginal Gel and Tablet, applied to the cervix of healthy participants. Participants who meet all inclusion and none of the exclusion criteria will be evaluated throughout the study.
The study will be conducted in 2 parts: Part A (single ascending dose) and Part B (multiple asc
This is a randomized, double-blind, placebo-controlled, single and multiple dose escalation first-in-human study in healthy female participants. The study is designed to assess the safety, tolerability and PK of ABI-2280 Vaginal Gel and Tablet, applied to the cervix of healthy participants. Participants who meet all inclusion and none of the exclusion criteria will be evaluated throughout the study. The study will be conducted in 2 parts: Part A (single ascending dose) and Part B (multiple ascending dose). Investigational Product (IP): ABI-2280 Presentation: Vaginal Gel and Vaginal Tablet Mode of administration: Intravaginal on the cervix Part A Up to approximately 32 participants will be enrolled in one of four cohorts-A1 to A4. Each cohort will consist of 8 participants (6 to receive a single dose of ABI-2280 and 2 to receive a single dose of placebo). No participant will be enrolled in more than one cohort. For all cohorts in Part A, two sentinel participants will be enrolled. Cohort A1: Participants will receive ABI-2280 vaginal gel, 0.01% or placebo gel Cohort A2: Participants will receive ABI-2280 vaginal gel, 0.03% or placebo gel Cohort A3: Participants will receive ABI-2280 vaginal gel 0.1% or placebo gel OR Cohort A3: Participant will receive ABI-2280 vaginal tablet, up to 0.3 mg or placebo tablet Cohort A4: Participants will receive ABI-2280 vaginal tablet, up to 1 mg or placebo tablet Dose levels in part A are: 0.01%, 0.03%, 0.1% of ABI-2280 vaginal gel or placebo gel and Vaginal tablet up to 0.3 mg and 1 mg of ABI-2280 or Placebo tablet Part B Up to approximately 16 participants will be enrolled into two cohorts-B1 and B2. Each cohort will consists of 8 participants (6 to receive ABI-2280 vaginal tablet and 2 to receive placebo). The following treatments are planned: Cohort B1: ABI-2280 Vaginal tablet, up to 0.3 mg or placebo tablet administered 3 times over a 1 week period. Cohort B2: ABI-2280 Vaginal Tablet, up to 1 mg or placebo tablet administered 3 times over a 1 week period. Cohort B1 and B2 will be enrolled sequentially and enrollment into next higher dose cohort will not begin until key safety and PK data up to Day 9 from at least 6 participants in the cohort B1 become available. Additionally, all available cumulative safety and PK data from earlier cohorts in Part A and B will also be reviewed by the safety monitoring committee. For Cohorts B1 and B2, participants may be admitted to the research unit on Days-1 and 4 and discharged on Days 2 and 6, respectively. Alternatively, they may be admitted to clinical research unit on Day-1 and discharged on Day 6. On Days 1 and 5 participants will receive the first and last doses and complete the procedures as detailed in schedule of assessment in the protocol.
Sponsors
Antiva Biosciences Inc.
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver)
Eligibility
Sex/Gender
All
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Women, 18 to 50 years old, with an intact uterus 2. Generally in good health with no clinically significant pulmonary, cardiac, gastroenterologic, neurologic, renal, musculoskeletal, rheumatologic, metabolic, neoplastic, or endocrine disease 3. Able and willing to use stringent methods of contraception from at least 1 month prior to the required abstinence period (up to Day 7) through to Day 28. 4. Agree to provide coital history at study visits, and any local adverse reactions for sexual partner 5. Agree to abstain from sexual activities such as oral sex or sexual intercourse, vaginal douching or insertion of any vaginal products other than the study drug for at least 48 hours prior to enrollment through 7 days after dosing 6. Generally regular menstrual cycles 7. Negative cervical screening test within 3 months of enrollment, and no history of cervical intraepithelial lesions at any time 8. Good physical and mental health on the basis of medical history, physical examination, clinical laboratory, ECG, and vital signs at screening and admission (day-1) 9. Willing and able to adhere to the study visit schedule, other protocol requirements, including pelvic examination and cervical image acquisition
Exclusion criteria
1. Pregnant women, plan to become pregnant in next 3 months, lactating females 2. History of cancer, except basal cell or squamous cell carcinoma of the skin 3. History of genital herpes with more than 3 outbreaks per year 4. Have an active pelvic infection 5. Current or recent abnormal vaginal discharge and/or abnormal vaginal bleeding, abortion or miscarriage within the 3 months prior to randomization 6. Any clinically significant immune suppressing condition 7. Taking medications like inhaled or oral corticosteroids, systemic immunomodulatory treatments, over-the-counter intra-vaginal preparation or any prescription that in the opinion of investigator can interfere with the interpretation of the results 8. Hypersensitivity to any component of placebo formulation excipients or other nucleoside analogues (such as cidofovir, etc.) 9. Menses expected to start within 7 days of dosing for participants in Part A or 14 days for participants in Part B 10. Participants who test positive for HIV, Hepatitis B, or Hepatitis C at screening 11. Substance or alcohol abuse, history of anaphylaxis, or severe allergy to any food, drug or other exposure
Outcome results
None listed