Phase 3 Trial to Evaluate the Efficacy and Safety of COL-1620 Vaginal Progesterone Gel

Study Overview
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Brief Summary
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The primary objective of this trial is to demonstrate the non-inferiority of the clinical pregnancy rate per embryo transfer to the historical standard value in in-vitro fertilization (IVF)/embryo transfer (ET) cycles in Japan (Japan Society of Obstetrics and Gynecology [JSOG] 2009 registry data: 24.3 percent [%]). The secondary objectives of this trial are to assess the biochemical pregnancy rate per ET, pharmacokinetics, and safety of COL-1620.

Official Title
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Open-label, Single-arm, Multicenter Phase III Trial to Evaluate the Efficacy and Safety of COL-1620 8% Vaginal Progesterone Gel for Luteal Phase Support in In-vitro Fertilization and Embryo Transfer (IVF/ET) Cycles in Japanese Women

Conditions
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Luteal Hormone Supplementation in In-vitro Fertilization, Embryo Transfer

Intervention / Treatment
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* Drug: COL-1620
* Drug: Gonadotropin-releasing hormone (GnRH) analogue
* Drug: Follicle-stimulating hormone (FSH)
* Drug: Human Chorionic Gonadotropin (hCG)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese race Woman with a history of infertility and in whom In-vitro fertilization and embryo transfer (IVF/ET) is indicated The controlled ovarian stimulation (COS) therapy is gonadotropin-releasing hormone (GnRH) analogue (agonist or antagonist) in combination with a follicle-stimulating hormone (FSH) containing preparation Healthy premenopausal woman aged between 20 and 45 years (inclusive) and wishing to conceive Body mass index (BMI) of 17.0 to 25.0 kilogram per square meter (kg/m^2) (inclusive) A negative pregnancy test (urinary beta-human chorionic gonadotropin [hCG]) prior to starting COS Normal cervical smear result (Papanicolaou [PAP] test: Negative for Intraepithelial Lesion or Malignancy [NILM] or [Atypical Squamous Cells of Undetermined Significance {ASC-US} and Human Papillomavirus {HPV} negative]) within 12 months prior to the date of informed consent. If not available, a cervical smear and HPV test will be performed as part of Screening No clinically significant abnormal findings in the screening hematology, biochemistry and urinalysis parameters Full comprehension of the study and voluntary written informed consent obtained in writing prior to any trial-related activities Exclusion Criteria: History of recurrent pregnancy loss (defined as 3 or more previous spontaneous abortions) History of 3 or more consecutive cancelled or failed (no clinical pregnancy) IVF/ET cycles Abnormal hemorrhage of the reproductive tract of undetermined origin Any contraindication to being pregnant and/or carrying a pregnancy to term (for example, malformations of sexual organs or fibroid tumors of the uterus incompatible with pregnancy) Uterine myoma requiring treatment Extra-uterine pregnancy within the last 3 months prior to the date of informed consent History or presence of intracranial tumor (for example, hypothalamic or pituitary tumor) Presence of or suspected gonadotropin- or estrogen-dependent malignancy (for example, ovarian, uterine or mammary carcinoma) Ovarian enlargement or cyst of unknown etiology Breast-feeding or lactation History of severe Ovarian Hyperstimulation Syndrome (OHSS) (Classification of OHSS Severity, as per Japan Reproductive/Endocrine Working Group) Known Human Immunodeficiency Virus (HIV)-positive status, or a history of or current active infection with Hepatitis B or C Known allergy or hypersensitivity to progesterone preparations or gonadotropin preparations and/or their excipients, or any contraindication to receive medication for controlled ovarian stimulation (for example, gonadotropin, GnRH analogues, combined oral contraceptive pill, as appropriate) History of or suspected alcohol or substance abuse within 5 years prior to the date of informed consent Clinically significant systemic disease (for example, insulin-dependent diabetes, epilepsy, severe migraine, acute porphyria, hepatic, renal or cardiovascular disease, severe corticosteroid-dependent asthma) Active thrombophlebitis, thromboembolic disorder or cerebral apoplexy, or a history of such conditions Other significant disease that in the Investigator's or Sub-Investigator's opinion would exclude the subject from the trial Participation in another clinical trial within 3 months prior to the date of informed consent or simultaneous participation in another clinical trial Legal incapacity or limited legal capacity

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COL-1620<br> | Drug: COL-1620<br>* The subjects will be administered with COL-1620 vaginal progesterone gel (1.125 grams of progesterone gel containing 90 milligram that is 8 percent [%] gel) vaginally once daily, from the day of ovum pick-up (OPU) until Week 12.<br>Drug: Gonadotropin-releasing hormone (GnRH) analogue<br>* Subjects will undergo conventional controlled ovarian stimulation (COS) therapy for in-vitro Fertilization and Embryo Transfer (IVF/ET) according to the Investigator's discretion using GnRH analogue (agonist or antagonist) preparation.<br>Drug: Follicle-stimulating hormone (FSH)<br>* Subjects will undergo conventional COS therapy for IVF/ET according to the Investigator's discretion using FSH containing preparation.<br>Drug: Human Chorionic Gonadotropin (hCG)<br>* Subjects will undergo conventional COS therapy for IVF/ET according to the Investigator's discretion using hCG preparation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Pregnancy Rate Per Embryo Transfer | Clinical pregnancy was defined as the presence of a fetal sac on transvaginal ultrasound (TVUS) during Week 5 or the presence of an extra-uterine pregnancy (as confirmed during surgery or by 2 positive serum beta-human chorionic gonadotropin (beta-hCG) results from Week 5). The clinical pregnancy rate was calculated as number of subjects who were clinically pregnant divided by the number of subjects who had at least 1 embryo transferred. | Week 5 post embryo transfer (2-6 days after Ovum Pick-up [OPU]) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical Pregnancy Rate Per Embryo Transfer | Biochemical pregnancy was defined as any miscarriage without any evidence of a fetal sac on TVUS during Visit 6 (Week 5), but with a positive serum beta-hCG pregnancy test result at Visit 5 (Day 14+/-3). Biochemical pregnancy rate was calculated as the number of subjects who had no fetal sac observed during Visit 6 (Week 5) TVUS assessment or subjects who had a positive serum pregnancy test at Visit 5 (Day 14+/-3) and no data recorded at Visit 6 (Week 5) divided by the number of subjects who has at least 1 embryo transferred. | Week 5 post embryo transfer (2-6 days after Ovum Pick-up [OPU]) | 
| Serum Progesterone Level | Two pharmacokinetic (PK) samples were collected per subject for the measurement of serum progesterone concentrations; 1st sample at Visit 2-2 (prior to hCG administration) and second sample during Visit 5 (Day 14+/-3, 7 hours after the morning of investigational medicinal product administration). | Visit 2-2 (Prior to hCG administration) and Visit 5 (Day 14+/-3) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infertility, COL-1620, progesterone gel, Fertilization in Vitro, Embryo Transfer