Clinical trial NCT05502367: A Study of ABI-2280 Vaginal Insert (Previously Referred to as ABI-2280 Vaginal Tablet) in Participants With Cervical Intraepithelial Neoplasia
Official title: An Open-Label Single and Multiple-dose, Study to Evaluate Safety, Tolerability and Efficacy of ABI-2280 Vaginal Insert (Previously Referred to as ABI-2280 Vaginal Tablet) in Participants With Cervical Squamous Intraepithelial Lesions
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Cervical Intraepithelial Neoplasia
Lead sponsor: Antiva Biosciences
Sponsor class: INDUSTRY
First posted: 2022-08-16
Enrollment: 110
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is an open-label study to evaluate the safety, tolerability, and efficacy of ABI-2280 in participants with cervical squamous intraepithelial lesions. This study is divided into 2 parts - Part A and Part B.

Part A consists of up to 9 dose escalation cohorts. Part B consists of dose expansion cohorts.

Participants will self-administer ABI-2280.


Eligibility criteria: Inclusion Criteria:

* Women, 25 to 55 years old.
* For Cohorts A1 and A2 in Part A, participants with biopsy-confirmed CIN (with visible lesions) regardless of p16 positivity may be enrolled upon consultation with PI and Medical Monitor. These participants will not be required to get LLETZ if not medically necessary, as determined by the PI in consultation with the Medical Monitor.
* For Cohorts A3 and above in Part A and Part B POC cohorts, biopsy-confirmed cHSIL that is p16+ (p16INK4a expressed) within 60 days of enrollment (dosing) with no evidence of invasive cancer in any specimen. If biopsy was performed ≥ 60 days before planned enrollment, participants must agree to have another biopsy performed at the Screening visit, unless approved by the Medical Monitor.
* A positive high-risk HPV (hrHPV) result by provider-obtained cervical swab at screening or previously obtained and documented within the past 3 months.
* No prior treatment for Cervical intraepithelial neoplasia (CIN).
* Generally, in good health with no clinically significant pulmonary, cardiac, gastro-enterologic, neurologic, renal, musculoskeletal, rheumatologic, metabolic, neoplastic, or endocrine disease.

Exclusion Criteria:

* Women who are pregnant, plan to become pregnant in the next 4 months, or lactating females.
* Unwilling to use stringent methods of contraception (including barrier method, as well as another acceptable method) throughout the course of the study.
* History of cancer, except basal cell or squamous cell carcinoma of the skin.
* History of genital herpes with outbreak within prior 12 months.
* Have an active pelvic or non-HPV (Human papillomavirus) vaginal infection (e.g., that was detected by a positive urine screen for gonorrhea or chlamydial infection, bimanual exam consistent with pelvic inflammatory disease, positive bedside testing criteria for bacterial vaginosis, candida vaginitis or trichomonal vaginitis, etc).
* Current or recent abnormal vaginal discharge and /or abnormal vaginal bleeding.
* Had a therapeutic abortion or miscarriage less than 3 months prior.
* Any clinically significant immune suppressing condition.
* Participants with a significant acute condition or any other condition that in the opinion of the Investigator might interfere with the evaluation of the study objectives.
* Women who, in the PI's judgment, would be harmed by the delay in undergoing definitive treatment as a result of study participation and the ABI-2280 Vaginal Tablet dosing schedule.
* Vaccination (even 1 dose) with a prophylactic HPV vaccine (i.e., Gardasil®, Gardasil®-9 or Cervarix®) in the last 3 months.
* Vaccination with a therapeutic HPV vaccine.

  * Other inclusion/exclusion criteria may apply

Primary outcomes:
measure: Incidence of Adverse Events (Safety and Tolerability)
timeFrame: From Baseline to Day 42 post dose administration
Secondary outcomes:
measure: Histopathologic changes in cHSIL by large loop excision of the transformation zone (LLETZ) speciment
timeFrame: 12 weeks after the first dose of ABI-2280 Vaginal Tablet
measure: Pharmacokinetics of ABI-2280 after single and multiple doses
timeFrame: PK time points will begin on Day 1 and will continue up to Day 49 (depending on the Cohort)
Other outcomes:
measure: Exploratory Endpoint
timeFrame: hrHPV testing to occur at baseline up to end of study (Day 84)
Locations:
city: Darlinghurst
country: Australia
facility: East Sydney Doctors
state: New South Wales
city: Cusco
country: Peru
facility: CerviCusco
city: Lima
country: Peru
facility: Ginobs S.A.
city: Bloemfontein
country: South Africa
facility: Farmovs
state: Free State
city: Sunnyside
country: South Africa
facility: Nafasi Integrated Solutions
state: Gauteng
city: Waltloo
country: South Africa
facility: Botho ke Bontle Health Services
state: Gauteng
city: Ga-Mothapo
country: South Africa
facility: Gole Biomedical Research Centre
state: Limpopo
Study officials:
References: