Blood loss from the uterus, while normal in the context of menses and immediately postpartum, can and frequently does exceed “normal”, leading to modest to severe disruptions in a woman’s physical, emotional, social, and material quality of life. Worldwide, it has been reported that approximately one third of women are affected at some time in their life by abnormal uterine bleeding (AUB). AUB is perhaps the most common medical affliction in women with Postpartum haemorrhaged (PPH) is the leading direct cause of maternal mortality worldwide.

In a study conducted at Moi Teaching and Referral Hospital in 2018-2019 study to characterize abnormal bleeding patterns in women in Western Kenya, results showed that (41.7%) of women had prolonged bleeding and (35%) heavy bleeding patterns.

Despite the medicinal or interventional approaches for AUB, there is need for a novel treatment option geared towards treatment of PPH and reduction in maternal morbidity and mortality, while providing a reliable, safe, affordable, low-technology solution for treatment for AUB.

As such, we aim to conduct a phase 1, single-site, double-blind, randomized, placebo-controlled trial to assess the safety and initial efficacy of Polidocanol (AHCO1) delivered into the uterus through transcervical catheter among (n=20) adult females aged (25 to 55-years) who are actively experiencing heavy uterine bleeding at Kenyatta National Hospital (KNH) for a period of 6 months.

Title: A phase 1, single-center, double-blind, randomized, placebo-controlled trial to assess the safety, tolerability, and initial efficacy of AHC01 delivered via transcervical catheter in adult females (25-55 years), experiencing abnormal uterine bleeding and scheduled for a hysterectomy.

Rationale: To contribute to the development of treatments for important causes of morbidity and mortality among women and investigate the efficacy of AHC01 in the treatment of PPH to reduce maternal morbidity and mortality, while providing a reliable, safe treatment for abnormal uterine bleeding (AUB)

Primary Objective:

1. To assess the safety of a single 100 mg intra-uterine dose of ACH01 in adult females (25-55 years) that:

 a) consider themselves family complete,

 b) are actively experiencing heavy menstrual bleeding, and

c) are scheduled for a hysterectomy.

2. Bioavailability -To understand what fraction of the dose delivered into the uterus is absorbed into systemic circulation.

Primary Endpoints-Safety

1. The number and severity of solicited systemic adverse events collected on the day of study product administration and daily until day 7 thereafter.
2. The number, severity and relatedness of unsolicited AE and SAE from the day of study product administration until end of study (~30 days)
3. The number, severity and relatedness of biochemical and hematologic abnormalities occurring from the day of study product administration until end of study (~30 day)
4. Bioavailability- Blood samples will be collected serially for evaluation of serum polidocanol levels.

Study Design: This is a phase 1, single-site, double-blind, randomized, placebo-controlled trial to assess the safety and initial efficacy of AHC01 delivered into the uterus via transcervical catheter in adult females actively experiencing heavy uterine bleeding and scheduled for a hysterectomy. Two study groups, each consisting of 10 individuals will be enrolled. Group 1 subjects (treatment group) will receive intrauterine AHC01 (IU-ACH01) and Group 2 subjects (placebo group) will receive intrauterine normal saline (PLA-IU). In all, 20 women (25 to 55-years-of-age, inclusive) will be randomized in a 1:1 ratio.

Study Site: Kenyatta National Hospital (KNH)

Number of Assessment: The study has five assessment visits namely:

1. V0- Screening visit
2. V1- Qualification Phase visit
3. V2 - Final eligibility, randomization, and study product administration
4. At all scheduled (V3, V4,) visits- At all scheduled (V3, V4,) visits

Study Duration: 6 months with 45-60 days study duration per participant.

Target Population: The trial seeks to treat a total of 20 adult females aged (25 to 55 years) as defined eligibility criteria (Section 5.2)

Statistical Analysis: The primary safety and BPAC data will be presented in groups based on treatment received (IU-ACH01 or IU-PLA). All safety data subsequently collected based on these groups will be included in the analysis irrespective of any subsequent protocol deviations. A supportive per protocol analysis to confirm the robustness of the findings will also be performed. Full details of the final statistical analysis will be set out in the statistical analysis plan (SAP) which will be finalized prior to database lock and unblinding.