PGL5001 Proof of Concept Study in Inflammatory Endometriosis

Study Overview
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Brief Summary
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This is a prospective, three-part (Part A1, Part A2 and Part B),Phase II study investigating the efficacy, safety, pharmacokinetics and pharmacodynamics of the JNK inhibitor PGL5001 orally administered for up to 5 months with concomitant DMPA administration for the treatment of laparoscopically diagnosed inflammatory endometriosis. The part A1 is open-label, the parts A2 and B are double-blind. The target population will be women of reproductive age and suffering from newly diagnosed peritoneal and/or ovarian endometriosis.

Official Title
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A Phase IIa Efficacy and Safety Study of PGL5001 Versus Placebo Administered for up to 5 Months With Concomitant Administration of Depot Medroxyprogesterone Acetate for the Treatment of Peritoneal and/or Ovarian Endometriosis With an Inflammatory Component.

Conditions
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Endometriosis

Intervention / Treatment
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* Drug: PGL5001
* Drug: Placebo
* Drug: PGL5001
* Drug: Placebo
* Drug: PGL5001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The Subject must provide written informed consent prior to initiation of any study related procedures. The Subject must be an adult woman of reproductive age, aged from 18 and above. The Subject must be a newly diagnosed patient suffering from peritoneal and/or ovarian endometriosis with at least 15% of the endometriotic lesions observed at the study diagnostic laparoscopy being red inflammatory lesions and with a proven histological diagnosis. The Subject must consent to the scheduling of a second laparoscopy for surgical treatment at the study end. The Subject must have a history of pelvic pain for at least 3 months prior to the screening visit. Exclusion Criteria: The Subject is over 40 years old and has a FSH serum level during Day 2-4 of her cycle ≥ 21.5 mIU/ml. The Subject has a positive pregnancy test at baseline or is breast-feeding or planning a pregnancy during the course of the study. The Subject is known for having a cause of chronic abdominal/pelvic pain other than endometriosis (e.g. inflammatory bowel disease, fibromyalgia, interstitial cystitis). The Subject has a history of surgical treatment for endometriosis prior to the study diagnostic laparoscopy. The Subject is requiring urgent surgical excision of endometriotic lesions at the time of first diagnostic laparoscopy. The Subject has a history (in the past 12 months) of or a current medical treatment for endometriosis other than NSAID (e.g. GnRH agonist or antagonist, danazol, continuous oral combined oestroprogestogens).

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Part A2 - Active Treatment arm<br>PGL5001 for 8 weeks + one DMPA injection | Drug: PGL5001<br>* PGL5001 320mg/day (160 mg twice a day) for 8 weeks + one unique DMPA 150 mg injection<br>|
| Placebo Comparator: Part A2 - Placebo Treatment arm<br>PGL5001 matching placebo for 8 weeks + one DMPA injection | Drug: Placebo<br>* PGL5001 matching placebo (twice a day) for 8 weeks + one unique DMPA 150 mg injection<br>|
| Active Comparator: Part B - Active treatment arm<br>PGL5001 for 20 weeks + two DMPA injections | Drug: PGL5001<br>* PGL5001 320mg/day (160 mg twice a day) for 20 weeks + DMPA 150mg injection. Second DMPA injection between 85 to 89 days after first injection<br>|
| Placebo Comparator: Part B - Placebo Treatment arm<br>PGL5001 matching placebo for 20 weeks + two DMPA 150mg injections | Drug: Placebo<br>* PGL5001 matching placebo (twice a day) for 20 weeks + DMPA 150mg injection. Second DMPA injection between 85 to 89 days after first injection<br>|
| Experimental: Part A1 - Active Treatment arm<br>PGL5001 for 8 weeks + one unique DMPA 150 mg injection | Drug: PGL5001<br>* PGL5001 320mg/day (160 mg twice a day) for 8 weeks + one unique DMPA 150 mg injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to end of treatment in the number and percentage of red lesions (and/or inflammatory lesions), based on total number of red and black lesions. |  | at week 8, week 20 |