Recombinant Follicle Stimulating Hormone (FSH) (Gonal-f®): Use in Ovulation Induction

NCT01081626 | Completed Phase 4 Results

• 1 other identifier: EMR 700623-501
• Study Type: interventional
• Target: 310
• Locations: 3 countries
• Sites: 3

Brief Summary

This is an open-label, prospective, randomized, controlled, multicentric, multinational, phase IV study to evaluate the use of Gonal-f in inducing ovulation in female subjects with chronic anovulation. It has been observed that conventional high dose set up regimen of gonadotropin and human chorionic gonadotropin (hCG) is effective in anovulatory subjects in terms of overall pregnancy rates. However, development of multiple follicles leading to multiple pregnancy and/or ovarian hyperstimulation syndrome (OHSS) is the major complications associated with this high dose set up. Chronic low-dose (CLD) protocols of follicle stimulating hormone (FSH), aimed at finding the threshold amount of FSH necessary to promote monofolliculogenesis, have been found to be successful in reducing the rate of OHSS almost to nil and the rate of multiple pregnancies to a minimum. This post-marketing study will investigate tailoring of recombinant follicle stimulating hormone (r-FSH) in a large population (N=310) of subjects from a region (North Africa/Middle East) that has not been included in previous studies of ovulation induction in subjects with chronic anovulation. The study aims to increase current knowledge of the efficacy and safety of Gonal-f, and provide fertility physicians with experience in Gonal-f treatment in anovulatory infertility, thereby contributing to the development of FSH dosing guidelines for ovulation induction by defining the optimal CLD and Low dose (LD) regimens.

Conditions

Ovulation Induction

Keywords

Infertility; Ovulation induction; Gonal-f; Follitropin alpha; Polycystic ovarian syndrome; Anovulatory infertility

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a Mono-follicular Development

  Mono-follicular development was defined as the development of only 1 follicle of greater than or equal to (\>=) 17 millimeter (mm) diameter and no more than 2 other follicles larger than 14 mm in diameter at or before Days 35-42 of stimulation period assessed by means of a transvaginal ultrasound scan.

  Day 0 (first dose) up to Days 35-42 post human chorionic gonadotropin [hCG] administration (end of stimulation cycle {less than or equal to [<=] 35 days})

Secondary Outcomes (10)

• Number of Participants With Multi-follicular Development

  Day 0 (first dose) up to Days 35-42 post hCG administration (end of stimulation cycle {less than or equal to [<=] 35 days})

• Number of Participants With Adverse Events (AEs)

  Day 0 (first dose) up to Days 35-42 post hCG administration (end of stimulation cycle {less than or equal to [<=] 35 days})

• Number of Participants With Multiple Pregnancies

  Day 0 (first dose) up to Days 35-42 post hCG administration (end of stimulation cycle {less than or equal to [<=] 35 days})

• Number of Participants With Injection Tolerability

  Day 0 (first dose) up to Days 35-42 post hCG administration (end of stimulation cycle {less than or equal to [<=] 35 days})

• Number of Participants Who Received Human Chorionic Gonadotropin (hCG)

  End of stimulation cycle (less than or equal to [<=] 35 days)

Study Arms (2)

Group I: Chronic Low dose Protocol

EXPERIMENTAL

Gonal-f will be injected on the second or third day of a spontaneous or progestogen-induced menstrual cycle (Day 0), with a daily dose of 75 International Units (IU) for 7 days. Ovarian response will be assessed on Day 7 of stimulation by ultrasound scan. If no follicle has reached at least 10 to 12 millimeter (mm) diameter, stimulation will be continued with the same dose for further 7 days. On Day 14 of stimulation, if no ovarian response is seen, the dose will be increased by 37.5 IU (total 112.5 IU) and administered for the next 7 days. Subsequent increments of 37.5 IU, at intervals of 7 days up to Day 35 of stimulation would be made, depending on ovarian response.

Drug: Recombinant FSH (follitropin alpha)

Group II: Low dose Protocol

EXPERIMENTAL

Gonal-f will be administered on the second or third day of a spontaneous or progestogen-induced menstrual cycle (Day 0), with a daily dose of 75 IU for 7 days. Ovarian response will be assessed on Day 7 of stimulation by ultrasound scan. If no follicle has reached at least 10 to 12 mm diameter, the dose will be increased by 37.5 IU (total 112.5 IU) and administered for the next 7 days. Subsequent increments of 37.5 IU, at intervals of 7 days up to Day 35 of stimulation will be made, depending on ovarian response.

Drug: Recombinant FSH (follitropin alpha)

Interventions

Recombinant FSH (follitropin alpha) DRUG

A starting dose of 75 IU and a first adjustment on Day 14 or Day 7 of stimulation in Group I and II respectively, if no ovarian response is observed.

Also known as: Gonal-f®, Follitropin alpha

Group I: Chronic Low dose Protocol; Group II: Low dose Protocol

Eligibility Criteria

• Age: 18 Years - 37 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Premenopausal female subjects, aged between 18 and 37 years inclusive
• Subjects willing to conceive
• Subjects who are infertile due to chronic anovulation demonstrated by a cycle duration of \> 35 days, or regular cycles with progesterone (P4) levels \< 1 nanomole/milliliter (nmol/mL) during luteal phase (Day 25)
• Subjects who have experienced spontaneous menses, menses induced by clomiphene citrate therapy, or a positive progestin-induced withdrawal within the previous year
• Subjects with FSH and PRL serum values within the normal range in the early follicular phase
• Subjects with total antral follicle count (AFC) \> 10 (of follicle size ≥ 2 mm and \< 11 mm) in both ovaries
• Subjects with at least 1 patent tube, as documented by recent (within 2 years before treatment assignment) hysterosalpingography (HSG)
• Subjects with normal uterine cavity, as documented by recent (within 2 years before treatment assignment) hysteroscopy, HSG or ultrasound scan
• Subjects with body mass index (BMI) \>20 and ≤32 kilogram square per meter (kg/m\^2)
• Subjects with negative cervical Papanicolaou (PAP) test within the 6 months prior to screening
• Male partners of female subjects with sperm compatible with non assisted fertilization
• Subjects who are willing and able to participate in the study and have provided written, informed consent

You may not qualify if:

• Subjects with history of hypersensitivity to the active substance follitropin alpha, FSH, or to any of the excipients of Gonal-f
• Subjects with ovarian enlargement or ovarian cyst unrelated to PCOS, and of unknown origin on ultrasound
• Subjects with evidence of diminished ovarian reserve (cycle length \< 26 days; FSH above the upper limit of local serum FSH values, total AFC in both ovaries \< 10)
• Subjects with myomatous uterus, which in the opinion of the investigator could impair pregnancy evolution
• Subjects who have undergone 3 or more previous miscarriages
• Subjects with any previous extrauterine pregnancy
• Pregnant or lactating female subjects
• Subjects with abnormal gynecological bleeding of unknown etiology
• Subjects with previous history of severe OHSS
• Subjects who have undergone operative pelvic surgery which could induce mechanical infertility (e.g tubes blockage) or pelvic inflammatory disease (PID) before treatment assignment excluding curettage and hysteroscopy
• Subjects with tumors of the hypothalamus and pituitary gland
• Subjects with ovarian, uterine or mammary carcinoma
• Subjects treated with clomiphene citrate or gonadotropins within 1 month of the screening evaluation
• Subjects with any medical condition which, in the opinion of the investigator, would prevent an effective response, such as primary ovarian failure, or malformations of the reproductive organs incompatible with pregnancy
• Subjects with any medical condition which, in the opinion of the investigator, may interfere with the absorption, distribution, metabolism or excretion of the drug

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead
• Merck Serono Middle East FZ-LLC, United Arab Emirates, an affiliate of Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (3)

New Mowasat Hospital

As Sālimīyah, P.O.Box 6661, 22077, Kuwait

Location

Mount Lebanon Hospital

Hazmiyeh, P.O.Box 470, Lebanon

Location

King Abdel Aziz University Hospital

Jeddah, P.O.Box 80215, 21589, Saudi Arabia

Location

Related Publications (1)

• Serour GI, Aboulghar M, Al Bahar A, Hugues JN, Esmat K. Phase IV, open-label, randomized study of low-dose recombinant human follicle-stimulating hormone protocols for ovulation induction. Reprod Biol Endocrinol. 2014 Jun 18;12:52. doi: 10.1186/1477-7827-12-52.

  PMID: 24942155 DERIVED

MeSH Terms

Conditions

Infertility; Polycystic Ovary Syndrome

Interventions

Glycoprotein Hormones, alpha Subunit; follitropin alfa

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Chorionic Gonadotropin; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Luteinizing Hormone; Pituitary Hormones, Anterior; Pituitary Hormones; Thyrotropin; Placental Hormones; Peptides; Amino Acids, Peptides, and Proteins

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

• Khaled Esmat, MD

  Merck Serono Middle East FZ-LLC, United Arab Emirates, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2010
• First Posted: March 5, 2010
• Study Start: March 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: February 13, 2014
• Results First Posted: November 7, 2012

Record last verified: 2014-01

Locations

LE (1); SA (1); KU (1)