Evaluate the Safety & Assess Local and Systemic PK of DS003 Vaginal Tablets Administered to Healthy HIV-negative Women

NCT02877979 | Completed Phase 1

• 1 other identifier: IPM 042
• Study Type: interventional
• Target: 36
• Locations: 0 countries
• Sites: N/A

Brief Summary

A double-blind, randomised, placebo-controlled, dose escalation trial to evaluate the safety and to assess local and systemic pharmacokinetics of ds003 vaginal tablets administered to healthy HIV-negative women.

Conditions

HIV

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety of three escalating doses of DS003 (1 mg, 3 mg and 10 mg), administered in a vaginal tablet formulation, to healthy, HIV-negative female volunteers.

  Gynaecological assessments, including pelvic examination and colposcopy

  12 weeks

Secondary Outcomes (1)

• To assess the local (vaginal fluids) and systemic (plasma) DS003 PK profile and the 24 hour cervical tissue concentration when administered in three escalating doses of a vaginal tablet formulation.

  12 weeks

Study Arms (2)

DS003 vaginal tablet

EXPERIMENTAL

participants will be randomised in a 3:1 ratio to receive either DS003 or placebo on Day 0 and Day 17.

Drug: DS003 vaginal tablet

placebo

PLACEBO COMPARATOR

participants will be randomised in a 3:1 ratio to receive either DS003 or placebo on Day 0 and Day 17.

Drug: Placebo

Interventions

DS003 vaginal tablet DRUG

The trial will be conducted in three cohorts of 12 women each. In each cohort, participants will be randomised in a 3:1 ratio to receive either DS003 or placebo on Day 0 and Day 17. In each cohort, therefore, 9 participants will receive DS003 vaginal tablets and 3 participants will receive placebo vaginal tablets.

DS003 vaginal tablet

Placebo DRUG

placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women must meet all of the following criteria to be eligible for enrolment:
• Women ≥ 18 and ≤ 45 years of age who can give written informed consent
• BMI of ≥ 18 and \< 30 kg/m2
• Vital signs within normal limits and no clinically significant ECG findings
• Available for all visits and consent to follow all procedures scheduled for the trial
• Healthy, based on medical history, vital signs, physical examination, urinalysis (dipstick and microscopy), laboratory evaluations for genital infections (bacterial vaginosis, gonorrhoea, chlamydia and trichomonas) and laboratory evaluations for haematology and biochemistry
• HIV-negative as determined by an HIV test at the time of screening
• On a stable form of contraception, defined as:
• A stable oral contraceptive regimen for at least 2 months prior to enrolment, OR
• Transdermal contraceptive patch for at least 3 months prior to enrolment, OR
• Subcutaneous implant inserted at least 3 months prior to enrolment, OR
• Long-acting progestins for at least 2 consecutive injections, OR An IUD inserted (with no vaginal or gynaecological complaints associated with its use) at least 3 months prior to enrolment, OR
• Have undergone surgical sterilisation at least 3 months prior to enrolment AND be willing to use oral contraceptives if necessary to delay menstruation while taking part in the trial
• Upon pelvic examination and colposcopy at screening and visual inspection of the cervix at the time of enrolment, the cervix and vagina appear normal as determined by the Investigator
• Asymptomatic for urogenital infections at the time of screening (if a woman is diagnosed with any curable STI, either clinically or by laboratory test at the time of screening, she must complete the full course of treatment and have a healthy genital tract before being considered for potential re-screening)

You may not qualify if:

• Currently pregnant or had their last pregnancy outcome within 3 months prior to screening
• Currently breast-feeding
• Currently or within 2 months of participation in any other clinical research trial involving investigational or marketed products prior to screening
• Untreated symptomatic urogenital infections, e.g. urinary tract or other sexually transmitted infections, or other gynaecological conditions such as vaginal itching, pain, or discharge, prior to enrolment
• Have a Grade 2 or higher pelvic examination finding, according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events; Addendum 1 Female Genital Grading Table for Use in Microbicide Studies
• History of significant urogenital or uterine prolapse, undiagnosed vaginal bleeding, urethral obstruction, incontinence or urge incontinence
• Current vulvar or vaginal symptoms/abnormalities that could influence the trial results
• Cervical cytology at screening that requires cryotherapy, biopsy, treatment, or further evaluation
• Symptomatic genital herpes simplex virus (HSV) infection or a history of genital herpetic infection
• Any Grade 2, 3 or 4 haematology, biochemistry or urinalysis laboratory abnormality at baseline (screening) according to the current version of the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events
• Unexplained, abnormal bleeding per vagina during or following vaginal intercourse, or gynaecologic surgery within 90 days prior to enrolment
• Any history of anaphylaxis or severe allergy resulting in angioedema; or a history of sensitivity/allergy to latex
• Any serious acute, chronic or progressive disease (e.g. any known history of neoplasm, cancer, diabetes, epilepsy, cardiac disease, autoimmune disease, HIV, AIDS, or blood dyscrasias), or signs of cardiac disease, renal failure, or severe malnutrition
• Have undergone a hysterectomy
• History of drug or substance abuse within 1 year of enrolment

Sponsors & Collaborators

• International Partnership for Microbicides, Inc.: lead

Related Publications (1)

• Herrera C, Harman S, Aldon Y, Rogers P, Armanasco N, Ziprin P, Stieh D, Nuttall J, Shattock RJ. The entry inhibitor DS003 (BMS-599793): a BMS-806 analogue, provides superior activity as a pre-exposure prophylaxis candidate. AIDS. 2021 Oct 1;35(12):1907-1917. doi: 10.1097/QAD.0000000000002974.

  PMID: 34101626 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2016
• First Posted: August 25, 2016
• Study Start: November 18, 2015
• Primary Completion: August 26, 2016
• Study Completion: August 26, 2016
• Last Updated: August 24, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share