A Study to Investigate Efficacy and Safety of OG-6219 BID in 3 Dose Levels Compared With Placebo in Participants Aged 18 to 49 With Moderate to Severe Endometriosis-related Pain

Study Overview
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Brief Summary
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The purpose of this global Phase 2 study is to determine the efficacy, safety, and tolerability of 3 dose levels of OG-6219 in pre-menopausal women between 18 and 49 years of age (inclusive), who have moderate to severe endometriosis-related pain.

Detailed Description
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This is a global multicenter, Phase 2a/b, randomized, double-blind, Placebo-controlled study to assess the efficacy, safety, and tolerability of 3 dose levels of OG-6219, in pre-menopausal women 18 to 49 years of age (inclusive), who have been surgically diagnosed with endometriosis with moderate to severe endometriosis-related pain. This study includes treatment lasting approximately 16 weeks in total and is followed by a Safety Follow-up. Pre-menopausal females aged 18 to 49 years old (inclusive), who have been surgically diagnosed with endometriosis will be screened to randomly assign to study treatment. A minimum subset of 10 participants per treatment group (including Placebo group) will be voluntarily enrolled for optional intensive PK sampling for the entire duration of the study.

Official Title
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A Phase 2a/b, Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter, Clinical Study to Evaluate the Efficacy and Safety of OG-6219 in 3 Dose Levels, in Women 18 to 49 Years of Age With Moderate to Severe Endometriosis-related Pain

Conditions
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Endometriosis

Intervention / Treatment
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* Drug: OG-6219
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pre-menopausal females of age 18 to 49 years old (inclusive) at the time of signing Informed Consent (V1). Surgically (laparoscopy or laparotomy) diagnosed with endometriosis Moderate to severe endometriosis-related pelvic pain Regular menstrual cycles Is not expected to undergo a planned gynecological surgery or other surgical procedures for treatment of endometriosis during study participation. Normal breast exam at V1 Agree not to participate in another interventional study while participating in the present study. Able and willing to adhere to study procedures, including agree to use 2 forms of non-hormonal contraception throughout the study Must be willing and able to provide signed informed consent before any study-related activities Has demonstrated compliance with ≥75% of eDiary entries Has a negative pregnancy test Exclusion Criteria: Surgical history of hysterectomy and/or bilateral oophorectomy Chronic pelvic and/or non-pelvic pain not caused by endometriosis that requires chronic analgesic or other chronic therapy Undiagnosed (unexplained), abnormal vaginal bleeding not associated with endometriosis within the past 6 months before screening. Presence of high-risk human papillomavirus (HPV). Has an active sexually transmitted infection (STI) (eg, gonorrhea, chlamydia, or trichomonas). Intends to become pregnant or breast feed during study participation or has a known or suspected pregnancy. History of malignancy ≤5 years except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. History of family history of hereditary abnormal hemoglobin or an enzyme deficiency that can result in methemoglobinemia. Has a medical condition associated with hemolytic anemia Known human immunodeficiency virus infection, with active, recurrent, or chronic infection (eg, hepatitis A, B, or C virus) Has a clinically significant abnormal ECG or QT interval prolongation Used any medication that is either a sensitive substrate, moderate, or strong inhibitor or inducer of CYP3A4 within 30 days or 10 half-lives (whichever is longer) prior to the planned first day of dosing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 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 |
| --- | --- |
| Experimental: OG-6219 Dose 1<br>OG-6219 Dose 1 BID | Drug: OG-6219<br>* OG-6219 Dose 1, Dose 2, Dose 3 BID: Participants will receive (orally) OG-6219 during treatment cycles.<br>|
| Experimental: OG-6219 Dose 2<br>OG-6219 Dose 2 BID | Drug: OG-6219<br>* OG-6219 Dose 1, Dose 2, Dose 3 BID: Participants will receive (orally) OG-6219 during treatment cycles.<br>|
| Experimental: OG-6219 Dose 3<br>OG-6219 Dose 3 BID | Drug: OG-6219<br>* OG-6219 Dose 1, Dose 2, Dose 3 BID: Participants will receive (orally) OG-6219 during treatment cycles.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Participants will receive (orally) OG-6219 Placebo tablets BID during treatment cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from first treatment cycle to last planned treatment cycle of the daily OPP score. | The OPP measures endometriosis-related pain using NRS with range 0(no pain) to 10(worst imaginable). | First treatment cycle to last planned treatment cycle, an average of 16 weeks (each cycle is approximately 28 days). | 
| Safety and tolerability of OG-6219 | Safety and tolerability of the treatment is assessed by proportion of participants who experienced any AEs/SAEs, by abnormalities in clinical laboratory assessments, vital signs, and physical examination, and by proportion of participants who prematurely discontinued study treatment due to AEs/SAEs. | First treatment cycle through completion of follow-up, an average of 20 weeks (each cycle is approximately 28 days). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from first treatment cycle to last planned treatment cycle of the daily DYS score |  | First treatment cycle through completion of last planned treatment cycle, an average of 16 weeks (each cycle is approximately 28 days). | 
| Mean change from first treatment cycle to last planned treatment cycle of the daily NMPP score |  | First treatment cycle through completion of last planned treatment cycle, an average of 16 weeks (each cycle is approximately 28 days). | 
| Mean change from first treatment cycle to remaining treatment cycles in daily number of tablets of rescue medication for endometriosis-related pain. |  | First treatment cycle through completion of last planned treatment cycle, an average of 16 weeks (each cycle is approximately 28 days). | 
| Mean change from first treatment cycle to remaining treatment cycles in the proportion of days participant has used rescue medication for endometriosis-related pain. |  | First treatment cycle through completion of last planned treatment cycle, an average of 16 weeks (each cycle is approximately 28 days). | 
| Mean change from Visit 1 to Visit 7 in serum hormone levels. |  | Screening through end of treatment, an average of 24 weeks. | 
| Mean change at Visit 5 and Visit 7 in serum hormone levels. |  | Visit 5 through Visit 7, an average of 9 weeks. | 
| Plasma concentrations of OG-6219 and FOR-1011 at scheduled assessments using sparse PK sampling during the treatment period. |  | First treatment cycle through completion of last planned treatment cycle, an average of 16 weeks (each cycle is approximately 28 days). | 
| Mean change from Visit 1 to Visit 7 in bone biomarker levels |  | Screening through end of treatment, an average of 24 weeks. | 
| Proportion of participants with clinical parameters of significance from Visit 1 to Visit 5, Visit 6, Visit 7, and Visit 8. |  | Screening through safety follow-up, an average of 28 weeks. | 
| Mean change from first treatment cycle to second, third and fourth treatment cycles in the percentage of days with vaginal bleeding |  | First treatment cycle through completion of last planned treatment cycle, an average of 16 weeks (each cycle is approximately 28 days). | 
| ECG parameter changes at each of the four treatment cycle visits |  | First treatment cycle through completion of last planned treatment cycle, an average of 16 weeks (each cycle is approximately 28 days). | 
| Change from first treatment cycle to last planned treatment cycle in the Mean EHP-30 Domain Scores |  | First treatment cycle through completion of last planned treatment cycle, an average of 16 weeks (each cycle is approximately 28 days). | 
| Mean change in dyspareunia as measured by NRS from eDiary from first treatment cycle to last planned treatment cycle. |  | First treatment cycle through completion of last planned treatment cycle, an average of 16 weeks (each cycle is approximately 28 days). | 
| Change in PGI-S score from first treatment cycle to second, third and fourth treatment cycles. |  | First treatment cycle through completion of last planned treatment cycle, an average of 16 weeks (each cycle is approximately 28 days). | 
| Percent of participants with any improvement on the PGI-C from first treatment cycle to last planned treatment cycle. |  | First treatment cycle through completion of last planned treatment cycle, an average of 16 weeks (each cycle is approximately 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endometriosis Related Pain (ERP), Endometriosis, Pre-menopausal women