PGL4001 Efficacy Assessment in Reduction of Symptoms Due to Uterine Leiomyomata

Study Overview
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Brief Summary
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This is a multicentre, Phase III, efficacy and safety open-label study with PGL4001 10mg once daily for 3 months, blinded towards the administration of progestin or placebo after end of PGL4001 treatment.

Detailed Description
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PGL4001 will be administered daily to all subjects in an open-label manner with no control group. The three months open label treatment period will be followed by a ten day double blind treatment with progestin or matching placebo. Subjects will be randomly assigned to progestin or matching placebo arm with a 1:1 ratio.

Official Title
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A Phase III, Multicentre, Clinical Study Investigating the Efficacy and Safety of 3-months Open-label Treatment With PGL4001, Followed by a Randomised, Double-blind Placebo Controlled Period of 10 Days Treatment With Progestin, in Subjects With Myomas and Heavy Uterine Bleeding.

Conditions
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Uterine Fibroids

Intervention / Treatment
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* Drug: PGL4001, placebo
* Drug: PGL4001, progestin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is a pre-menopausal woman aged between 18 and 48 years inclusive. Subject with a Body Mass Index ≥18 and ≤40. Subject with myomatous uterus size < 16 weeks. Subject must have at least one uterine myoma of at least 3 cm diameter in size and no myoma larger than 10 cm diameter diagnosed by ultrasound. Subject complained of strong uterine bleeding. Subject is eligible for hysterectomy or myomectomy. Females of childbearing potential have to practice a non-hormonal method of contraception. Exclusion Criteria: Subject has a history of or current uterus, cervix, ovarian or breast cancer. Subject has a history of endometrium hyperplasia or adenocarcinoma in a biopsy performed within the past 6 months or similar lesions in the screening biopsy. Subject has a known severe coagulation disorder. Subject has a history of treatment for myoma with a SPRM, including ulipristal acetate. Subject has abnormal hepatic function at study entry.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 48 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Drug: PGL4001 10mg (oral tablets) for 3 months followed by a period of 10 days of placebo (oral tablets). | Drug: PGL4001, placebo<br>* PGL4001 10mg once daily (oral tablets) for 3 months followed by a period of 10 days of placebo (oral tablets).<br>* Other names: Ulipristal acetate;|
| Experimental: B<br>Drug: PGL4001 10mg (oral tablets) for 3 months followed by a period of 10 days of progestin (oral tablets). | Drug: PGL4001, progestin<br>* PGL4001 10mg once daily (oral tablets) for 3 months followed by a period of 10 days of progestin Norethisterone acetate 10mg once daily (oral tablets).<br>* Other names: Ulipristal acetate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy endpoints | Investigate efficacy of PGL4001 on uterine bleeding (% of subjects in amenorrhea at end of PGL4001 treatment), myoma size (transvaginal ultrasound), pain (short Mc Gill questionnaire) and quality of life (specific UFS-QoL questionnaire and general EQ-5D questionnaire). | From baseline to end of PGL4001 treatment (3months treatment) and to approximately 2 weeks after double blind treatment with progestin/placebo. | 
| Number and proportion of subjects experiencing open label treatment-emergent adverse events |  | From baseline to end of PGL4001 treatment (3months treatment) |