A First-in-human Safety Trial of BNT331 Administered as Single Ascending Doses in Healthy Women and as Multiple Ascending Doses in Women Diagnosed With Bacterial Vaginosis

Bacterial Vaginosis Clinical Trial

Official title:

A Phase I Randomized, Double-blind, Placebo-controlled, Safety, Tolerability, and Pharmacokinetic Trial of BNT331 Administered in Single Ascending Doses in Healthy Women and Multiple Ascending Doses in Women Diagnosed With Bacterial Vaginosis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06469164
• Other study ID #: BNT331-01
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: July 2024
• Est. completion date: May 2025

Study information

• Verified date: June 2024
• Source: BioNTech SE
• Contact: BioNTech clinical trials patient information
• Phone: +49 6131 9084
• Email: patients[@]biontech.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a two-part, randomized, double-blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy (for Part B) of BNT331 in healthy women (Part A) and in women diagnosed with bacterial vaginosis (BV) (Part B).

Description:

Part A will include single ascending dose levels and will assess the safety of BNT331 and describe the incidence of adverse events (AEs) for participants randomized at a ratio of 3:1 to BNT331 or placebo. Participants will receive one single dose of study treatment.

Part B will include multiple ascending dose levels. Participants will be randomized at a ratio of 2:1 to BNT331 or placebo. Participants with BV will receive study treatment for five consecutive days.

The vaginal inserts will be self-administered by the participant. The participants will receive detailed instructions from the investigator on how to self-administer the vaginal inserts at home.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 96
• Est. completion date: May 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have given written informed consent by signing and dating the informed consent form (ICF) before initiation of any study-specific procedures.

• Participant reported assigned female sex at birth, at least 18 years of age and pre-menopausal, as determined by the investigator.

• Not menstruating or having vaginal bleeding:

• Part A and Part B: At Visit 0 and Visit 1 and do not expect to menstruate within the study period.

• Part B only: At Visit 0 and Visit 1 and do not expect to menstruate within the next 6 days, until the Early Response Visit (Visit 2).

• Part A only: Are healthy according to screening procedures. Part B only: Participants suffering from BV but who are otherwise healthy in the clinical judgement of the investigator.

• Note: Participants with pre-existing stable disease (e.g., obesity, hypertension, etc.), defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 90 days before Visit 0, can be included.

• Part A only: Should not have any clinical signs of BV as assessed by the absence of all Amsel's criteria and a normal Nugent score at screening, or other vaginal symptoms, including symptomatic vulvo-vaginal candidiasis (VVC) or infection with sexually transmitted infection (STI) pathogens including Chlamydia trachomatis, Trichomonas vaginalis, or Neisseria gonorrhoeae.

• Able to participate in the study as an outpatient, to attend all required visits, and to comply with all study requirements.

• Women of childbearing potential must have a negative highly sensitive urine pregnancy test result prior to study treatment initiation.

• The participant must have been on the same form of highly effective contraception for at least 3 months prior to dosing (Visit 1) and must agree to keep this method until:

• Part A: 60 days after Follow-up Visit (Visit 3)

• Part B: at least 60 days after Test of Cure (ToC) Visit (Visit 3).

• Women of childbearing potential who agree not to donate or cryopreserve eggs (ova, oocytes) for the purposes of assisted reproduction during study:

• Part A: Within 3 months prior to dosing (Visit 1) and continuously until 60 days after Follow-up Visit (Visit 3)

• Part B: Starting at Visit 0 and continuously until the Late Follow-up Visit (Visit 5).

• Agree to abstain from vaginal intercourse until:

• Part A: The Follow-up Visit (Visit 3)

• Part B: For the duration of treatment (~5 days) and until ToC Visit (Visit 3).

• Agree to not use any vaginal products, e.g., creams, gels, foams, sponges, douches, and tampons (except during menstruation), until:

• Part A: The Follow-up Visit (Visit 3)

• Part B: ToC Visit (Visit 3).

• Part B only: Have a clinical diagnosis of BV, defined as having all the following Amsel's criteria (4/4):

1. Off-white (milky or gray), thin, homogeneous vaginal discharge.

2. Vaginal pH >4.5.

3. Presence of clue cells =20% of the total epithelial cells/high power field on microscopic examination of the vaginal saline wet mount.

4. A positive 10% KOH Whiff test.

• Part B only: Have a sample collected within 72 h prior to first dose for a Gram stain slide to assess Nugent score by the central laboratory.

Exclusion Criteria:

• Pregnant, lactating, or planning to become pregnant during their study participation and for at least:

• Part A: 60 days after Follow-up Visit (Visit 3)

• Part B: 60 days after ToC Visit (Visit 3).

• Have genital lesions, including active herpes simplex virus or syphilitic lesions, or other vaginal or vulvar conditions.

• Part A only: Have active STI.

• Had received antifungal or antimicrobial therapy (in Part A, systemic or topical; in Part B, systemic or vaginal) within 14 days prior to the Visit 1.

• Are using a Copper intrauterine device, or any vaginal hormonal products (including NuvaRing®) as a form of contraception.

• Had a history of drug or alcohol abuse within the past 12 months, as determined by the investigator.

• Had participated in any investigational study within 30 days before the Visit 1 or is currently participating or plans to participate in any investigational, or observational study.

• Has any history of allergies, hypersensitivities, or intolerance to the study treatments including any excipients thereof.

• Has any history of an abnormal Pap smear which required cervical biopsy and/or cervical cauterization within 6 months of Visit 1

• Malignancy within 5 years of screening, including but not limited to cervical carcinoma and carcinomas of the vagina and vulva.

• Has any condition including psychiatric illnesses that could interfere with their ability to understand or comply with the requirements of the study as determined by the investigator.

• Part B only: Currently suspected clinically (or confirmed diagnostically) of having alternative causes of vaginal disease symptoms including symptomatic VVC or infection with STI including Chlamydia trachomatis, Trichomonas vaginalis, or Neisseria gonorrhoeae.

Related Conditions & MeSH terms

• Bacterial Vaginosis
• Vaginal Diseases
• Vaginosis, Bacterial

Intervention

Drug:
• BNT331
Vaginal insert

Other:
• Placebo
Vaginal insert

Locations

Country	Name	City	State
United States	Nucleus Network	Saint Paul	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
BioNTech SE

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A - Percentage of participants with adverse events (AEs) with onset after first treatment dose and until the Follow-up Visit	In participants who have received at least one dose of BNT331 or placebo. For each dose level cohort of BNT331 and for the combined placebo group.	from first dose of study treatment up to 12 days post-dose
Primary	Part B - Percentage of participants with adverse events (AEs) with onset after first treatment dose and until Late Follow-up Visit	In participants who have received at least one dose of BNT331 or placebo. For each dose level cohort of BNT331 and for the combined placebo group.	from first dose of study treatment up to 127 days post-first dose
Primary	Part A - Percentage of participants with serious adverse events (SAEs) with onset after first treatment dose and until the Follow-up Visit	In participants who have received at least one dose of BNT331 or placebo. For each dose level cohort of BNT331 and for the combined placebo group.	from first dose of study treatment up to 12 days post-dose
Primary	Part B - Percentage of participants with SAEs with onset after first treatment dose and until the Late Follow-up Visit	In participants who have received at least one dose of BNT331 or placebo. For each dose level cohort of BNT331 and for the combined placebo group.	from first dose of study treatment up to 127 days post-first dose
Secondary	Part A - Serum concentrations of BNT331 active substance at pre-specified timepoints	For each dose level cohort of BNT331. In participants who received one single administration.	from pre-dose up to 12 days post-dose
Secondary	Part B - Serum concentrations of BNT331 active substance at pre-specified timepoints	For each dose level cohort of BNT331. In participants who received all scheduled administrations.	from pre-dose up to 30 days post-first dose
Secondary	Part A - Anti-drug antibody (ADA) prevalence or change of binding titers against BNT331 active substance in blood before study treatment and at the Follow-up Visit	For each dose level cohort of BNT331	from pre-dose up to 12 days post-dose
Secondary	Part B - ADA prevalence or change of binding titers against BNT331 active substance in blood before study treatment and at the Test of Cure (ToC) Visit	For each dose level cohort of BNT331	from pre-dose up to 30 days post-first dose
Secondary	Part B - Number of participants with clinical cure	For each dose level cohort of BNT331 and for the combined placebo group. Normalization of the vaginal discharge, a negative potassium hydroxide (KOH) "Whiff" test, and clue cells <20% of the total epithelial cells/high power field on microscopic examination of the vaginal fluid.	from 6 days post-first dose up to 30 days post-first dose
Secondary	Part B - Number of participants with Nugent score cure/Microbiological cure	For each dose level cohort of BNT331 and for the combined placebo group. Nugent score of <4.	from 6 days post-first dose up to 30 days post-first dose
Secondary	Part B - Responder outcome - Number of participants with clinical cure and normal Nugent score of <4	For each dose level cohort of BNT331 and for the combined placebo group.	from 6 days post-first dose up to 30 days post-first dose