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
- Trial ID
- 2022-501310-57-00
- Protocol
- OG-6219-P001
- Sponsor
- Organon LLC
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical study is to evaluate the **efficacy** of three dose levels of OG-6219 (Groups A, B, C) compared to a placebo (Group D) in reducing overall pelvic pain associated with **endometriosis** during Treatment Cycle 3 (TRC3). This is measured using a Numeric Rating Scale (NRS) in an electronic diary. Additionally, the study aims to assess the safety and tolerability of OG-6219. The clinical relevance of this objective lies in addressing the significant pain management needs of women suffering from moderate to severe endometriosis-related pain, potentially offering a new therapeutic option.
Secondary objectives include:
- Evaluating the efficacy of OG-6219 in reducing dysmenorrhea, non-menstrual pelvic pain, and dyspareunia during TRC3, as measured by NRS in the eDiary.
- Assessing the daily use of rescue medication for endometriosis-related pain across treatment cycles.
- Evaluating changes in Patient Global Impression of Severity (PGI-S) and Change (PGI-C) scores at various time points.
- Assessing changes in the Endometriosis Health Profile-30 (EHP-30) domains from baseline to TRC3.
- Evaluating clinically significant changes in bone biomarkers and laboratory parameters over specified visits.
- Assessing vaginal bleeding patterns over three menstrual cycles as recorded in the eDiary.
- Evaluating potential changes in Electrocardiogram (ECG) parameters and serum hormone concentrations at specified visits.
- Assessing the pharmacokinetics (PK) of OG-6219 and its active metabolite FOR-1011.
Participants
The clinical trial involves a total of **28 participants** who are pre-menopausal females aged between **18 to 49 years**. The study population is specifically selected to evaluate the efficacy and safety of OG-6219 in reducing endometriosis-related pelvic pain. Participants were chosen based on their diagnosis of endometriosis, confirmed through surgical methods such as laparoscopy or laparotomy within the last 4 months to 10 years prior to the screening visit. The trial includes individuals who have experienced moderate to severe endometriosis-related pelvic pain, as measured by a numeric rating scale, and who have demonstrated compliance with study procedures, including eDiary entries and placebo tablet intake. Participants are required to have a regular menstrual cycle and are not expected to undergo any planned gynecological surgery during the study. The trial exclusively involves female subjects, and the population is considered vulnerable. Lifestyle considerations such as diet and physical activity are not specified, but participants must agree to use non-hormonal contraception and adhere to study protocols, including the use of study-provided rescue medication for pain management.
Plans and Procedures
The clinical trial is a **Phase 2a/b**, randomized, double-blind, placebo-controlled, parallel group, multicenter study designed to evaluate the efficacy and safety of OG-6219 in women aged 18 to 49 years with moderate to severe **endometriosis-related pain**. The trial involves three dose levels of OG-6219 and a placebo group, with the primary objective of assessing the reduction in overall pelvic pain during the third treatment cycle, as measured by a numeric rating scale in an electronic diary. The trial is expected to run from May 24, 2023, to December 20, 2024.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, pain severity, and compliance with eDiary entries. Following the screening, participants will enter a placebo run-in phase to ensure adherence to study protocols. Randomization occurs at Visit 4, where participants are assigned to one of the treatment groups. Subsequent visits will monitor safety, efficacy, and compliance, with assessments including transvaginal ultrasound, ECG, and pharmacokinetic sampling. The end-of-study visit will conclude the trial, evaluating the overall outcomes and any adverse events experienced by participants.
The expected length of participant involvement is approximately 94 days, with conditions for early termination including non-compliance with study procedures, adverse events, or withdrawal of consent. Participants are required to adhere to study protocols, including the use of non-hormonal contraception and the exclusive use of study-provided rescue medication for pain management. The trial's design ensures rigorous monitoring and data collection to achieve its objectives while maintaining participant safety and data integrity.
Treatment
The clinical trial involves the administration of **OG-6219**, an experimental medication, in the form of a tablet. The active substance in OG-6219 is **FOR-6219**, a chemical compound. The pharmaceutical form is a standard tablet, and the route of administration is oral. Participants will receive OG-6219 in three different dose levels, designated as Groups A, B, and C, to evaluate its efficacy and safety in reducing moderate to severe endometriosis-related pain. The maximum treatment period for OG-6219 is 94 days. The dosing schedule and specific dosage amounts are not detailed in the provided data.
In addition to the experimental medication, a **placebo** tablet is used as a comparator treatment in this study. The placebo is designed to match the OG-6219 tablet in appearance and is administered orally. Participants in Group D will receive the placebo to assess the efficacy of OG-6219 against a non-active control. The placebo administration follows the same schedule as the experimental medication, ensuring blinding and maintaining the integrity of the study design.
Furthermore, **Nalgesin S**, a non-experimental treatment, is included in the trial. Nalgesin S contains **naproxen sodium** as its active substance and is provided in the form of film-coated tablets. The route of administration is oral. Although the specific role of Nalgesin S in the trial is not explicitly stated, it may serve as an auxiliary treatment to manage pain symptoms. The maximum treatment period for Nalgesin S is 6 days, and the dosing schedule is not specified in the available data.
Participant compliance with the medication regimen will be monitored throughout the trial. The study is designed to ensure that all treatments, including the experimental medication, placebo, and any auxiliary treatments, are administered consistently and according to the protocol. This approach aims to accurately assess the efficacy and safety of OG-6219 in the target population.
Efficacy
The efficacy of OG-6219 in the treatment of moderate to severe **endometriosis-related pain** will be assessed through a series of primary and secondary endpoints. The primary efficacy endpoint is the change from the baseline cycle (BC) to Treatment Cycle 3 (TRC3) in the mean Overall Pelvic Pain (OPP) score, as measured by a Numeric Rating Scale (NRS) in the eDiary. Secondary endpoints include changes from BC to TRC3 in the mean dysmenorrhea (DYS) score, non-menstrual pelvic pain (NMPP) score, and dyspareunia score. Additionally, changes in the mean number of tablets of rescue medication for endometriosis-related pain (ERP) and the proportion of days participants use rescue medication will be evaluated across TRC1, TRC2, and TRC3.
Further secondary endpoints involve changes in the Patient Global Impression of Severity (PGI-S) score from Visit 4 to subsequent visits, and the percentage of participants with any improvement in the Patient Global Impression of Change (PGI-C) at TRC1, TRC2, and TRC3. The study will also assess changes in the Endometriosis Health Profile-30 (EHP-30) Domain Scores, mean changes in bone biomarker levels from Visit 1 to Visit 7, and clinical parameters of significance from Visit 1 to Visit 8. Serum hormone levels and plasma concentrations of OG-6219 and FOR-1011 will be measured at scheduled assessments using sparse pharmacokinetic (PK) sampling during the treatment period, with intensive PK sampling conducted on Visit 4 and Visit 5 to determine Cmax, Tmax, and AUCtau for both compounds.
Inclusion and Exclusion Criteria
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 within the last 4 months to 10 years prior to Screening Visit (V1), as documented by medical records
- Has moderate to severe endometriosis-related pelvic pain in recent menstrual cycle(s) using a cutoff score of ≥4 in a numeric rating scale (NRS) and likely meets eligibility criterion # 10 at Randomization Visit (V4)
- Has had spontaneous (ie, without hormonal therapy), regular, menstrual cycle with a cycle length between 21 to 32 days (inclusive) for the past 1 month before V1
- Is not expected to undergo a planned gynecological surgery or other surgical procedures for treatment of endometriosis during study participation.
- Has a normal breast examination at V1. In participants of ≥40 years mammography or contrast-enhanced breast magnetic resonance imaging (MRI) performed within the last 12 months prior to Screening (V1) without clinically significant abnormal findings.
- Agrees not to participate in another interventional study while participating in the present study.
- Is able and willing (in the opinion of the Investigator) to adhere to all required study procedures, including: a) Study visits schedule, b) Agree to switch from their usual analgesic to ONLY the rescue medication provided by the study and agree to discontinue their hormone treatment for ERP as outlined in Table 2 of the protocol. c) Agree to timely and duly complete eDiary entries, d) To cooperate and comply with the protocol requirements, including, Transvaginal ultrasound (TVUS), ECG, PK, and pharmacodynamic (PD) assessment among others. e) Agree to use 2 forms of non-hormonal contraception throughout the study (from V1 thorough V8). f) Not planning to relocate during the study (such that the participant would not be able to continue participation at the study site).
- Must be willing and able to provide signed informed consent before any study-related activities.
- At Visit 4: Has moderate to severe ERP, determined by the NRS (0 to 10 anchored, with 0 [no pain] and 10 [extremely severe pain]), at V4 (before Randomization), based on the eDiary entries from the participant’s last menstrual cycle (BC), as follows: a) An OPP (DYS and NMPP) score of ≥4, OR b) For DYS at least 2 days with ≥4 and NMPP score of ≥4 on at least 7 days (not necessarily consecutive), OR c) For DYS at least 2 days with ≥4 and NMPP score of ≥7 on at least 3 days (not necessarily consecutive).
- At Visit 4: Has demonstrated compliance with ≥75% of eDiary entries (ie, pelvic pain score, vaginal bleeding, rescue medication intake) during both the screening cycle (SC) and the BC.
- At Visit 4: Is ≥80% compliant with the Placebo tablets over the BC (Placebo Run-in), as determined by tablet accountability at the site.
- At Visit 4: Has taken only the study provided rescue medication, at a dose not exceeding the maximum dose determined by the Investigator, for control of ERP during the BC as evidenced in the eDiary.
- Have a negative pregnancy test as outlined in the Schedule of activity of the protocol
Exclusion Criteria
- Has a surgical history of hysterectomy and/or bilateral oophorectomy.
- Has chronic pelvic and/or non-pelvic pain NOT CAUSED by endometriosis that requires chronic analgesic or other chronic therapy (including, but not limited to, pain caused by interstitial cystitis, bladder pain syndrome, irritable bowel syndrome, hysteroscopic sterilization, adenomyosis [as confirmed by previous MRI], vaginismus, chronic pelvic infection, fibromyalgia, chronic headaches, chronic back pain). Participants using or who will be using frequent opioid analgesics, cannabis, or non-opioids analgesics for chronic pain or recurring pain other than that due to ERP should also be excluded.
- Has a clinically significant gynecologic condition identified in the screening (including, but not limited to, endometriomas larger than 4 cm, complex ovarian cysts larger than 3 cm, simple ovarian cysts larger than 5 cm, single fibroid larger than 4 cm, symptomatic submucosal fibroid of any size, polyp >2 cm, hyperplasia, or endometrial cancer or any clinically significant endometrial pathology).
- Has a history of ERP that was not responsive at all (refractory) to treatment with CHCs, GnRH agonists and antagonists, progestins, or aromatase inhibitors alone or in combination. The participant that required >2 weeks of continuous use of narcotics for treatment of ERP within 6 months of V1 should also be excluded.
- Had undiagnosed (unexplained), abnormal, vaginal bleeding not associated with the baseline condition (endometriosis) within the past 6 months before screening.
- Has an active sexually transmitted infection (STI) (eg, gonorrhea, chlamydia, or trichomonas) is exclusionary
- Has no documented normal Papanicolaou (PAP) test within the timeline of current standard of care guidelines or has a significantly abnormal PAP test at Screening (V1) (low grade squamous intraepithelial lesion, high grade squamous intraepithelial lesion, atypical glandular cells [any type], squamous cell carcinoma, or adenocarcinoma [in situ or invasive]). The presence of high-risk human papillomavirus (HPV), regardless of PAP result, is exclusionary (e.g. atypical squamous cells)
- Intends to become pregnant during study participation or has a known or suspected pregnancy or has a positive β hCG or urine pregnancy test at any time before randomization.
- Has a history of malignancy (except basal cell or squamous cell skin cancer) before signing informed consent. Note: Any history of hormonal sensitive malignancy (e.g., breast or ovarian cancers) excludes the participant
- Has a history or family history of a hereditary abnormal hemoglobin or an enzyme deficiency that can result in methemoglobinemia (with an alteration in skin; color, pale, gray, or blue), or after receiving certain common drugs (ie, benzocaine, lidocaine, sulfonamides).
- Has a medical condition associated with hemolytic anemia such as sickle cell anemia, thalassemia, glucose-6-phosphate dehydrogenase deficiency, thrombotic thrombocytopenic purpura among other conditions previously diagnosed and confirmed.
- Has an allergy/sensitivity/intolerance to rescue medication provided by Sponsor or any contraindication to its use and in the setting of coronary artery bypass grafting surgery, or has experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other Nonsteroidal anti-inflammatory drug (NSAIDs)
- Has a history or current evidence of any unstable medical condition (including cardiovascular, bone, musculoskeletal, thyroid, diabetes), or other circumstance that in the opinion of the Investigator might confound the results of the study, affect participant’s safety or well-being, or interfere with the participant’s participation for the full duration of the study
- Has a known human immunodeficiency virus infection, and/or an acute or active, recurrent/relapsing or chronic infection (eg, hepatitis A, B, or C virus)
- Has a gastrointestinal, liver, kidney, or other disorder that would significantly interfere with the absorption, distribution, metabolism, or excretion of drugs in the opinion of the Investigator
- Has a clinically significant abnormal ECG or QT interval prolongation at Screening Visit (V1) or Randomization Visit (V4). Any participant with the following conditions must be excluded: a) A marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc interval >450 milliseconds) b) A history of additional risk factors for Torsade de Pointes (eg, heart failure, hypokalemia, family history of Long QT Syndrome) c) Use of concomitant medications that prolong the QT/QTc interval (such as but not limited to: ibutilide, quinidine, imipramine, erythromycin, and droperidol).
- Plans to schedule elective surgery during the study execution or had surgery in the past 4 months before screening that continues to require pain management.
- Suspected active Coronavirus Disease 2019 (COVID-19) infection a) Have tested positive for severe acute respiratory syndrome–related coronavirus 2 (SARS-CoV-2) based on a validated test per local guidelines at Screening and Baseline b) Have to comply with quarantine requirements per local Public Health directive
- Has been vaccinated with live or live-attenuated virus vaccine within 30 days prior to Screening
- Has an uncontrolled hypertension as diagnosed by participant’s treating physician.
- Has any of the following abnormal laboratory values at Screening a)Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase >2 × upper limit of normal (ULN) Alkaline Phosphatase >1.5 × ULN, provided cholestatic or other liver disease is excluded b) Total bilirubin (TBL) >1.0 × ULN (participants with Gilbert’s syndrome can be enrolled if other liver function tests are within stated limits)c) Impaired renal function as indicated by estimated glomerular filtration rate <30 mL/min/1.73 m2 (CKD-EPI 2009 calculation) d)Hemoglobin <10 gm/dL, white blood cell count <2500 mm3, neutrophil count <1500 mm3, platelet count <100 × 103/mm3.
- Based on the known metabolism of OG-6219 there are no effects of alcohol, caffeine, or tobacco associated with study treatment. However, during the study participants are asked to refrain from: a) Excessive tobacco use and smoking (including cannabis-derived and cannabis-related compounds based on Investigator’s discretion). Note: Short term use (ie, ≤ 3 days per cycle) of cannabis-derived and cannabis-related compounds are permitted. b) Active use of illicit drugs and/or alcohol abuse/dependance, as determined by the Investigator.
- Has a prior or current history of drug or alcohol abuse disorder according to Diagnostic and Statistical Manual of Mental Disorders 5 (DSM5).
- Has undergone blood transfusion within 2 weeks of V1. In addition, has lost ≥1 unit of blood (approximately 300 mL) within 8 weeks before the first dose of OG-6219.
- Use of treatments that might interfere with the conduct of the study or interpretation of the results
- Used any medication listed in the protocol 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. Participants must not consume other substances known to be potent inhibitors or inducers of CYP P450s such as grapefruit or Seville oranges containing products in 2 weeks before the planned first dose of study treatment administration.
- Current or a history of psychiatric disorder in the 3 years prior to Screening that would, in the opinion of the Investigator, affect the ability to participate in the study or would impair interpretation of data. Participants with current major depression, posttraumatic stress disorder, bipolar disorder, schizophrenia, or other psychotic disorders are excluded. Participant has a history of suicidal ideation or attempt within 3 years of Screening (V1).
- Has been a participant in an investigational drug or device study within 30 days prior to the Screening Visit.
- A study site employee or relative of a study site employee.
- Participant is pregnant, breast feeding, or planning a pregnancy within the next 7 months.
- Participants has received any treatment listed in the table of Prohibited Medication and Other Substances more recently than the “Last Allowable Use”, as indicated in the table, or must continue to receive any treatment listed in that table during the study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 24 May 2023 | 19 |
 Bulgaria | Not Recruiting | 24 May 2023 | 30 |
 Czechia | Not Recruiting | 24 May 2023 | 11 |
 France | Not Recruiting | 24 May 2023 | 3 |
 Germany | Not Recruiting | 24 May 2023 | 3 |
 Hungary | Not Recruiting | 24 May 2023 | 5 |
 Italy | Not Recruiting | 24 May 2023 | 3 |
 Latvia | Not Recruiting | 24 May 2023 | 16 |
 Poland | Not Recruiting | 24 May 2023 | 258 |
 Sweden | Not Recruiting | 24 May 2023 | 4 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo Tablet for OG-6219 | Placebo | N/A | — | — | — | N/A |
Nalgesin S 275 mg plėvele dengtos tabletės | Other | PLĖVELE DENGTOS TABLETĖS | ORAL | 00 | 6 | PRD2541114 |