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

NCT01863680 | Completed Phase 3 Results

• 1 other identifier: EMR200113_001
• Study Type: interventional
• Target: 178
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Luteal Hormone Supplementation in In-vitro Fertilization; Embryo Transfer

Keywords

Infertility; COL-1620; progesterone gel; Fertilization in Vitro; Embryo Transfer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Biochemical Pregnancy Rate Per Embryo Transfer

  Week 5 post embryo transfer (2-6 days after Ovum Pick-up [OPU])

• Serum Progesterone Level

  Visit 2-2 (Prior to hCG administration) and Visit 5 (Day 14+/-3)

Study Arms (1)

COL-1620

EXPERIMENTAL

Drug: COL-1620; Drug: Gonadotropin-releasing hormone (GnRH) analogue; Drug: Follicle-stimulating hormone (FSH); Drug: Human Chorionic Gonadotropin (hCG)

Interventions

COL-1620 DRUG

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.

COL-1620

Gonadotropin-releasing hormone (GnRH) analogue DRUG

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.

COL-1620

Follicle-stimulating hormone (FSH) DRUG

Subjects will undergo conventional COS therapy for IVF/ET according to the Investigator's discretion using FSH containing preparation.

COL-1620

Human Chorionic Gonadotropin (hCG) DRUG

Subjects will undergo conventional COS therapy for IVF/ET according to the Investigator's discretion using hCG preparation.

COL-1620

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (5)

Research site

Fujimino, Japan

Location

Research site

Kobe, Japan

Location

Research site

Osaka, Japan

Location

Research site

Sagamihara, Japan

Location

Research site

Yokohama, Kanagawa, Japan

Location

MeSH Terms

Conditions

Infertility

Interventions

Gonadotropin-Releasing Hormone; Follicle Stimulating Hormone; Chorionic Gonadotropin

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Gonadotropins, Pituitary; Gonadotropins; Pituitary Hormones, Anterior; Pituitary Hormones; Placental Hormones; Pregnancy Proteins

Limitations and Caveats

This study was not a randomized controlled study and did not included an active control arm, however it was designed to allow for comparison with historical IVF-ET data from Japan.

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Serono, a division of Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck Serono Co., Ltd., Japan

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2013
• First Posted: May 29, 2013
• Study Start: July 1, 2013
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: December 21, 2015
• Results First Posted: December 21, 2015

Record last verified: 2015-11

Locations

JP (5)