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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 354
- 试验地点
- 170
- 主要终点
- Safety and tolerability of OG-6219
研究概览
简要总结
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.
详细描述
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 visit.
Pre-menopausal females aged 18 to 49 years old (inclusive), who have been surgically diagnosed with endometriosis will be screened and randomly assigned 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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 V
- •In participants of ≥40 years mammography or contrast-enhanced breast MRI performed within the last 12 months prior to Screening (V1) without clinically significant abnormal findings.
- •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
排除标准
- •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 (except for basal cell or squamous cell skin cancer) before signing informed consent.
- •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, and/or acute or active, recurrent/relapsing, 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.
研究组 & 干预措施
Group D: Placebo
Group D: Placebo BID
干预措施: Placebo (Drug)
Group B: OG-6219 Dose 2
Group B: OG-6219 Dose 2 BID
干预措施: OG-6219 (Drug)
Group A: OG-6219 Dose 1
Group A: OG-6219 Dose 1 BID
干预措施: OG-6219 (Drug)
Group C: OG-6219 Dose 3
Group C: OG-6219 Dose 3 BID
干预措施: OG-6219 (Drug)
结局指标
主要结局
Safety and tolerability of OG-6219
时间窗: First treatment cycle through completion of follow-up, an average of 20 weeks (each cycle is approximately 28 days).
Safety and tolerability of the treatment is assessed by proportion of participants who experienced any AEs/SAEs, abnormalities in clinical laboratory assessments, vital signs, and physical examination, and by proportion of participants who prematurely discontinued study treatment due to AEs/SAEs.
Change from first treatment cycle to last planned treatment cycle in the mean OPP (endometriosis-related overall pelvic pain) score. The OPP measures endometriosis-related pain using NRS with range 0 (no pain) to 10 (worst imaginable).
时间窗: First treatment cycle to last planned treatment cycle, an average of 16 weeks (each cycle is approximately 28 days).
次要结局
- Change from first treatment cycle to last planned treatment cycle in the mean(First treatment cycle through completion of last planned treatment cycle, an average of 16 weeks (each cycle is approximately 28 days).)
- Change in Patient Global Impression of Severity (PGI-S) Score from V4 to Phone Contact 1, V6, and V7.(Visit 4 through V7, an average of 12 weeks (each cycle is approximately 28 days).)
- Percentage of participants with any improvement on the Patient Global Impression of Change at second, third and last planned treatment cycle.(Visit 4 through V7, an average of 12 weeks (each cycle is approximately 28 days).)
- Change from first treatment cycle to last planned treatment cycle in the Endometriosis Health Profile-30 (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)
- Change from first treatment cycle to remaining treatment cycles in the mean number of tablets of rescue medication for endometriosis-related pain (ERP) and in the proportion of days participant has used rescue medication for ERP.(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).)
- Mean change from V1 to V7 in serum hormone levels(Screening through end of treatment, an average of 24 weeks)
- Cmax, for both OG-6219 and FOR-1011.(At 2 visits approximately 3 weeks apart beginning at second treatment cycle.)
- Tmax for both OG-6219 and FOR-1011(At 2 visits approximately 3 weeks apart beginning at second treatment cycle)
- AucTAU for both OG-6219 and FOR-1011(At 2 visits approximately 3 weeks apart beginning at second treatment cycle)
- Change from first treatment cycle to last planned treatment cycle in the mean 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 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).)
- Plasma concentrations of OG-6219 and FOR-1011 at scheduled assessments using sparse PK sampling.(Second treatment cycle through completion of last planned treatment cycle, an average of 12 weeks (each cycle is approximately 28 days).)
- Change from first treatment cycle to last planned treatment cycle in the mean dyspareunia score.(First treatment cycle through completion of last planned treatment cycle, an average of 16 weeks (each cycle is approximately 28 days).)
- 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.)
- Serum hormone levels at V7 comparing each treatment group(At V7 approximately 24 weeks after patient consents to the study.)
- Mean change from Visit 1 to Visit 7 in bone biomarker levels(Screening through end of treatment, an average of 24 weeks.)
- Serum hormone levels at V5 comparing each treatment group(Visit 5)