Low-dose Gonal-f® in Ovulation Induction

NCT01871532 | Terminated Phase 4 Results

• 2 other identifiers: EMR700623_5352012-003227-38
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 10

Brief Summary

This is a prospective, multicenter, open-label, comparative and parallel-group study of ovulation induction evaluating tailoring of Recombinant follicle stimulating hormone (FSH) treatment using the Gonal-f® prefilled pen in World Health Organization (WHO) Type 2 anovulatory subjects who have previously failed to conceive with clomifene treatment.

Conditions

Infertility; Monofollicular Development

Keywords

Monofollicular Development; Gonal-f®; Recombinant Follicle Stimulating Hormone; Ovarian hyperstimulation syndrome (OHSS)

Outcome Measures

Primary Outcomes (1)

• Percentage of Cycles With Monofollicular Development

  The monofollicular development was defined as the number of cycles with monofollicular development only one Follicle Greater Than or Equal (\>= to 17 millimeter (mm) and no other follicles Greater than or equal to 14 mm following up to 4 weeks Gonal-f treatment.

  Baseline up to 4 weeks

Secondary Outcomes (14)

• Percentage of Cycles With Bifollicular Development

  Baseline up to 4 weeks

• Percentage of Cycles With Multifollicular Development

  Baseline up to 4 weeks

• Percentage of Ovulatory Cycles

  Baseline up to 42 days post human chorionic gonadotrophin (hCG) administration

• Percentage of Cycles Wherein Human Chorionic Gonadotropin (hCG) Was Not Administered

  Baseline up to 4 weeks

• Percentage of Cycles Resulting in Clinical Pregnancy

  35-42 days post hCG administration

Study Arms (2)

Low Dose Gonal-f® Protocol

EXPERIMENTAL

Gonal-f was administered subcutaneously daily at a starting dose of 50 International unit (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, with a final increase of 25 IU, up to maximum dose of 100 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion.

Drug: Gonal-f®

Standard Low Dose Gonal-f® Protocol

ACTIVE COMPARATOR

Gonal-f was administered subcutaneously daily at a starting dose of 50 International Units (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, up to maximum dose of 125 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion.

Drug: Gonal-f®

Interventions

Gonal-f® DRUG

Also known as: Recombinant follicle stimulating hormone (r-FSH)

Low Dose Gonal-f® Protocol; Standard Low Dose Gonal-f® Protocol

Eligibility Criteria

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

You may qualify if:

• Subjects eligible for ovulation induction treatment, where monofollicular development is the desired treatment outcome and the dose schedule outlined in the protocol is deemed appropriate
• Premenopausal female subjects, aged between 18 and 37 years inclusive
• Subjects desirous of pregnancy/willing to conceive
• Subjects who are infertile due to chronic anovulation demonstrated by cycle duration of greater than 35 days.
• Subjects who have been treated with clomifene citrate therapy, according to standard site practice, and have failed to ovulate and/or conceive
• Subjects with follicle stimulating hormone (FSH) and prolactin (PRL) serum values within the normal range in the early follicular phase
• Subjects with an overall total antral follicle count greater than 10 (of follicle size greater than or equal to 2 millimeter \[mm\] and less than 11 mm) (that is, total between both ovaries)
• Subjects with at least one patent tube, as documented by recent (within 2 years before treatment assignment) hysterosalpingography (HSG) or hysterosalpingo contrast sonography (HyCoSy)
• 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) greater than 20 and less than or equal to 32 kilogram per square meter (kg/m\^2) (BMI is equal to body weight \[kilogram {kg}\] divided by Height \* Height \[square meter {m\^2}\])
• Subjects with negative cervical Papanicolaou (PAP) test conducted according to national guidelines and/or standard site practice
• Male partners of female subjects with sperm compatible with non-assisted fertilization or availability of donor sperm, as confirmed by the Investigator
• Subjects who are willing and able to comply with protocol requirements and have provided written, informed consent

You may not qualify if:

• Subjects with history of hypersensitivity to the investigational medicinal product (IMP) (active substance follitropin alpha, FSH, or to any of the excipients of Gonal-f®) or any other drug used in the trial (that is, Ovitrelle)
• Subjects with ovarian enlargement or ovarian cyst unrelated to Polycystic Ovary Syndrome (PCOS), and of unknown origin on ultrasound
• Subjects with evidence of diminished ovarian reserve (cycle length less than 26 days; FSH above the upper limit of local serum FSH values, total antral follicle count \[AFC\] in both ovaries less than 10)
• Subjects with uterine pathology/abnormalities, which in the opinion of the Investigator could impair pregnancy evolution
• Subjects who have undergone three 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 ovarian hyper stimulation syndrome (OHSS) (after clomifene treatment)
• Subjects who have evidence of current or previous pelvic inflammatory disease before treatment assignment
• Subjects with tumors of the hypothalamus and pituitary gland
• Subjects with ovarian, uterine or mammary carcinoma
• Subjects treated with clomifene 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

Study Sites (10)

Research Site

Cork, Ireland

Location

Research Site

Dublin, Ireland

Location

Research Site

Galway, Ireland

Location

Research Site

Cambridge, United Kingdom

Location

Research site

Cheshunt, United Kingdom

Location

Research Site

Derby, United Kingdom

Location

Research Site

Edinburgh, United Kingdom

Location

Research Site

Glasgow, United Kingdom

Location

Research site

London, United Kingdom

Location

Research Site

Nottingham, United Kingdom

Location

MeSH Terms

Conditions

Infertility; Ovarian Hyperstimulation Syndrome

Interventions

follitropin alfa; Glycoprotein Hormones, alpha Subunit

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases; 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

Limitations and Caveats

Study was terminated because of delays in sourcing replacement Investigational Medicinal Product (IMP) for the study due to manufacturing delays hence the outcome measure was not assessed.

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck Serono Limited, UK

  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: June 4, 2013
• First Posted: June 6, 2013
• Study Start: July 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: November 1, 2014
• Last Updated: August 11, 2016
• Results First Posted: August 11, 2016

Record last verified: 2016-06

Locations

GB (7); IE (3)