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

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

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.

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