Safety and Efficacy Study in in Vitro Fertilisation (IVF) Patients

Safety and Efficacy Study Comparing a New hMG Formulation (hMG-IBSA) to a Reference Product (Menopur®) in Patients Undergoing Ovarian Stimulation for in Vitro Fertilisation (IVF)

The purpose of the non-inferiority study is to evaluate the clinical efficacy and the safety of two different subcutaneous hMG preparations when administered to patients undergoing controlled ovarian stimulation for IVF.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Drug: Menotropins

• Study Type: Interventional
• Enrollment (Actual): 270
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen
    • Hvidovre, Copenhagen, Denmark, 2650
      • Fertility clinic at Hvidovre Hospital
  • Odensee C
    • Odense, Odensee C, Denmark, 5000
      • Odense Universitetshospital
• France
  • Paris, France, 75014
    • Groupe Hospitalier Cochin - Saint Vincent de Paul
• Hungary
  • Budapest, Hungary, 1088
    • First Dept. Obstetric and Gynaecology, Semmelweiss University
• Switzerland
  • BS
    • Basel, BS, Switzerland, 4031
      • Universitatsspital Basel
• United Kingdom
  • West Midlands
    • Aldridge, West Midlands, United Kingdom, WS9 8LT
      • Midland Fertility Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women undergoing ovarian stimulation for IVF with the following characteristics:

  • Able and willing to sign the Patient Consent Form and adhere to the study visitation schedule
  • >18 and <40 years old
  • BMI between 18 and 30 kg/m2
  • less than 3 previously completed IVF cycles (i.e. completed cycle = egg recovery)
  • basal FSH <10 IU/L and E2 <80 pg/ml (~290 pmol/l)
  • Within 12 months of the beginning of the study, uterine cavity consistent with expected normal function as assessed through transvaginal ultrasound, hysterosalpingogram, sonohysterogram or hysteroscopic examination
  • Successful down-regulation performed with a standard GnRH-Agonist long protocol (Criteria for successful down-regulation: endometrial thickness < 7mm or serum E2 level <50 pg/ml (~185 pmol/l).

Exclusion Criteria:

• age <18 and >40 years
• primary ovarian failure or women known as poor responders (i.e. requiring more than 225 IU of hMG as a starting dose in previous treatment cycles or having less than 3 oocytes retrieved, or with a pre-ovulatory E2 serum concentration <500pg/ml (~1800 pmol/l))
• PCOS
• one or both ovaries inaccessible for oocyte retrieval
• ovarian cysts >10 mm
• hydrosalpinx that have not been surgically removed or ligated;
• stage 3 or 4 endometriosis
• oocyte donation
• implantation of previously frozen embryos
• patients affected by pathologies associated with any contraindication of being pregnant
• hypersensitivity to the study medication
• abnormal bleeding of undetermined origin
• uncontrolled thyroid or adrenal dysfunction
• neoplasias
• severe impairment of renal and/or hepatic function
• use of concomitant medications that might interfere with study evaluations (e.g. non-study hormonal medications, prostaglandin inhibitors, psychotropic agents)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: hMG-IBSA; New hMG preparation.	Drug: Menotropins; Daily administration, SC, starting dose 150 IU or 225 IU depending on patient age.
ACTIVE_COMPARATOR: Menopur	Drug: Menotropins; Daily administration, SC, starting dose 150 IU or 225 IU depending on patient age.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Total Number of Oocytes Retrieved	up to 24 days after treatment start

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean hMG Dose (Total);		up to 22 days after treatment start
Embryo Quality (Percentage of Patients With at Least One Top Quality Embryo)	Assessed by counting the total number of embryos obtained, the number of embryos transferred, frozen and discarded.	up to 28 days after treatment start
Positive b-hCG Test		up to 5 weeks after treatment start
Controlled Ovarian Stimulation Duration (Days)		up to 23 days after treatment start
17-β Estradiol (E2) Serum Concentration on the Monitoring Day Before hCG Injection;		up to 23 days after treatment start
Implantation Rate	defined as the mean of the total number of implanted embryos (presence of gestational sac assessed by ultrasound) divided by the total number of transferred embryos x 100;	10-11 weeks after embryo transfer
Clinical Pregnancy Rate,	defined as a pregnancy showing ultrasound embryonic heart activity at 10 - 11 weeks after embryo transfer;	10 - 11 weeks after embryo transfer
Number of Mature (Grade III Metaphase II) Oocytes Retrieved.		at the end of the stimulation.
Ratio Mature/Total Number of Oocytes Retrieved.	Percentage of retrieved oocytes considered to be mature.	at the end of the stimulation.
Total Number of Inseminated Oocytes (IVF and ICSI)	number of oocytes that were inseminated via IVF or injected via ICSI technique.	on the day of oocyte retrieval
Number of Cleaved Embryos		two days after insemination
Live Birth Rate		9 months after treatment

Collaborators and Investigators

• Sponsor: IBSA Institut Biochimique SA
• Investigators: Principal Investigator: Dominique De Ziegler, MD, Prof, Hopital Cochin

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (ACTUAL): April 1, 2013
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: March 7, 2011
• First Submitted That Met QC Criteria: March 9, 2011
• First Posted (ESTIMATE): March 11, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): July 22, 2016
• Last Update Submitted That Met QC Criteria: June 10, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Physiological Effects of Drugs; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Menotropins
• Other Study ID Numbers: 10EU/hMG02; 2010-021021-13 (EUDRACT_NUMBER)