A Trial to Compare the Efficacy and Safety of Ovarian Stimulation With GONAL-f® and Luveris® Starting on Day 1 Versus Day 6 in Women Undergoing Assisted Reproductive Technique

NCT01497197 | Terminated Phase 3 Results

• 1 other identifier: EMR200061-506
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase IIIb, interventional, multicenter, multinational, randomised, open-label, comparative trial which primary objective is to generate data on the ovarian stimulation profile obtained when Luveris® is started either on Day 1 or Day 6 in women in advanced reproductive age (36-42) undergoing Assisted Reproductive Technique (ART).

Conditions

Infertility; Fertility; Follicle Stimulating Hormone Deficiency

Keywords

Reproduction Techniques; Reproductive Medicine; Assisted Reproductive Technics; Pregnancy Rate; Ovulation Induction; Ovarian Stimulation; Oocytes; Implantation

Outcome Measures

Primary Outcomes (1)

• Total Number of Oocytes Retrieved Per Subject Following Ovarian Stimulation

  Ovarian stimulation was performed using in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). The total number of oocytes collected per subject following stimulation was reported.

  34-38 hours post r-hCG administration

Secondary Outcomes (10)

• Total Dose and Mean Daily Dose of Follicle Stimulating Hormone (FSH)

  Screening

• Total Number of Stimulation Treatment Days

  6 days post stimulation (Number of stimulation days+6 days)

• Implantation Rate

  35-42 days post r-hCG administration

• Number of Fetal Sacs With Activity

  35-42 days post r-hCG administration

• Number of Fetal Sacs With Detectable Heart Beats

  35-42 days post r-hCG administration

Study Arms (2)

Gonal-f®+Luveris®

EXPERIMENTAL

GONAL f® 300 international units \[IU\] per day as subcutaneous injection using liquid pen from stimulation Day 1-5 followed by Luveris® 150 IU per day lyophilized powder for subcutaneous injection from stimulation Day 1 until required recombinant human chorionic gonadotropin (r-hCG) level is met. The dose will be adjusted from stimulation Day 6 (increased or decreased) based upon the subject's ovarian response and according to the center's standard practice.

Drug: GONAL-f®; Drug: Luveris®; Biological: Recombinant human chorionic gonadotropin (r-hCG)

Gonal-f® Followed by Luveris®

EXPERIMENTAL

GONAL-f® 300 IU per day as subcutaneous injection using liquid pen from stimulation Day 1-5 followed by Luveris® 150 IU per day lyophilized powder for subcutaneous injection from stimulation Day 6 until required r-hCG level is met. The dose will be adjusted from stimulation Day 6 (increased or decreased) based upon the subject's ovarian response and according to the center's standard practice.

Drug: GONAL-f®; Drug: Luveris®; Biological: Recombinant human chorionic gonadotropin (r-hCG)

Interventions

GONAL-f® DRUG

GONAL f® 300 international units \[IU\] per day as subcutaneous injection using liquid pen.

Gonal-f® Followed by Luveris®; Gonal-f®+Luveris®

Luveris® DRUG

Luveris® 150 IU per day lyophilized powder for subcutaneous injection.

Gonal-f® Followed by Luveris®; Gonal-f®+Luveris®

Recombinant human chorionic gonadotropin (r-hCG) BIOLOGICAL

A single injection of r-hCG (Ovidrel®/Ovitrelle®) 250 mcg to induce final oocyte maturation.

Gonal-f® Followed by Luveris®; Gonal-f®+Luveris®

Eligibility Criteria

• Age: 36 Years - 42 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Should be a female subject justifying an In Vitro Fertilization/Embryo transfer (IVF)/ET treatment
• Should be between 36th and 42nd birthday (both included) at the time of the randomization visit
• Have early follicular phase (day 2-4) serum level of basal FSH \<= 12 IU/L measured in the center's local laboratory during the screening period (i.e. within 2 months prior to down regulation start)
• Have a regular spontaneous ovulatory menstrual cycle between 21 and 35 days in length
• Presence of both ovaries
• Normal uterine cavity, which in the investigator's opinion is compatible with Pregnancy
• Have a negative cervical Papanicolaou (PAP or smear) test within the last 6 months prior to randomization
• Have at least one wash-out cycle (defined as \>=30 days since the last dose of clomiphene citrate or gonadotrophin treatment) since the last ART cycle and/or clomiphene citrate or gonadotrophin treatment prior to starting GnRH agonist therapy
• Be willing and able to comply with the protocol for the duration of the trial
• Have given written informed consent, prior to any trial-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to her future medical care
• Have a male partner with semen analysis within the past 6 months prior to randomization considered adequate to proceed with regular insemination or intra-cytoplasmic sperm injection (ICSI) according to the center's standard practice

You may not qualify if:

• Had 2 (or more) previous ART cycles with a poor response to gonadotrophin stimulation defined as 6 (or less) mature follicles and/or 4 (or less) oocytes collected in any previous IVF cycle or previous cycles with a hyper response defined as 25 (or more) oocytes retrieved
• Any medical condition, which in the judgment of the investigator may interfere with the absorption, distribution, metabolism or excretion of the drug. In case of doubt, the subject in question should be discussed with Merck Serono's Medical responsible
• Had previous severe ovarian hyperstimulation syndrome (OHSS)
• Polycystic ovary syndrome (PCOS; Rotterdam criteria) to reduce the risk of the occurrence of OHSS
• Presence of endometriosis requiring treatment
• Uterine myoma requiring treatment
• Any contraindication to being pregnant and/or carrying a pregnancy to term
• Extra-uterine pregnancy within the last 3 months prior to screening
• History of 3 or more miscarriages (early or late miscarriages) due to any cause
• Tumours of the hypothalamus and pituitary gland
• Ovarian enlargement or cyst of unknown etiology
• Ovarian, uterine or mammary cancer
• A clinically significant systemic disease
• Known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or C virus in the trial subject or her male partner
• Abnormal gynecological bleeding of undetermined origin

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead
• Merck Serono Middle East FZ LLC: collaborator

Study Sites (1)

Merck Serono Research Site

Dubai, United Arab Emirates

Location

MeSH Terms

Conditions

Infertility

Interventions

follitropin alfa; Luteinizing Hormone, beta Subunit; Chorionic Gonadotropin

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Luteinizing Hormone; Gonadotropins, Pituitary; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Peptides; Amino Acids, Peptides, and Proteins; Placental Hormones; Pregnancy Proteins; Proteins

Limitations and Caveats

Study was terminated as per sponsor's decision.

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 Director

  Merck Serono Middle East FZ LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2011
• First Posted: December 22, 2011
• Study Start: May 1, 2012
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: November 9, 2015
• Results First Posted: November 9, 2015

Record last verified: 2015-10

Locations

AE (1)