Investigation of a Long Acting Follicle Stimulating Hormone in Women Undergoing Assisted Reproductive Technology (ART)

Condition(s) targeted: Infertility

Intervention: AS900672-Enriched (Drug); Gonal-f RFF® (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: EMD Serono

Official(s) and/or principal investigator(s):
Zourab Bebia, MD, Study Director, Affiliation: EMD Serono

Study to evaluate a new investigational long-acting follicle stimulating hormone in infertile women who are undergoing an assisted reproductive technology procedure (IVF/ICSI). This study will compare three doses of the investigational drug vs a currently marketed medication (Gonal-f® RFF Pen) in regards to the number of fertilized eggs.

Official title: A Phase II, Multicenter, Randomized, Assessor-Blinded, Active-Comparator, Dose-Finding Study to Evaluate AS900672 Enriched Versus Follitropin Alfa (Gonal-f®) in Stimulating Multiple Follicular Development in Infertile Women Undergoing Assisted Reproductive Technology (ART)

Study design: Treatment, Randomized, Single Blind (Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Number of fertilized oocytes.

Secondary outcome: Clinical Pregnancy data 3 weeks after the embryo transfer

Detailed description: Infertile women who are candidates for ART will be prospectively screened for enrollment at approximately 26 clinical trial sites in the United States, Chile and Argentina. Enrolled subjects will start treatment using oral contraceptives (OCP) and will then receive a GnRH-agonist (leuprolide acetate) for pituitary desensitization. Once down-regulation is achieved, the subjects will be randomized in a 1: 1:1: 1 ratio to begin ovarian stimulation with one of three doses of AS900672 Enriched or with follitropin alfa (Gonal-f®) daily injections. Subjects will be recruited to the four study arms in parallel. Beginning on stimulation day 1 (S1), the subjects will receive either a single injection of AS900672 Enriched or start daily injections of follitropin alfa. The subjects' response to treatment will be monitored by ovarian ultrasound (US) and estradiol (E2) levels. On stimulation day 6 (S6), subjects randomized to AS900672 Enriched may begin receiving supplemental follitropin alfa 150 IU, according to the each subject's ovarian response, and subjects randomized to follitropin alfa 150 IU daily injections will continue treatment at the same dose. Recombinant human chorionic gonadotropin (r hCG, Ovidrel®) will be administered to subjects meeting response criteria and who are not at risk for OHSS. Oocyte retrieval will occur within 34-38 hours after hCG administration and subjects will begin luteal phase support using vaginal progesterone (Crinone 8%® or Prochieve ® 8%) the following day. Fertilization will be done by conventional in vitro fertilization (IVF) or intra-cytoplasmic sperm injection (ICSI). Embryo transfer will occur in accordance with the specific requirements of each subject and the clinical trial site's standard practice, with the exception that a maximum of two embryos at the cleavage or blastocyst stage may be transferred. Subjects who undergo embryo transfer will be assessed for pregnancy and a follow-up visit will be performed 15-20 days post hCG administration. Subjects with a positive pregnancy test will

undergo a confirmatory ultrasound evaluation at day 35 - 42 post hCG. Additionally, all

subjects recruited at certain trial centers will participate in a pharmacokinetic (PK) sub-study..

Minimum age: 18 Years. Maximum age: 36 Years. Gender(s): Female.

Criteria:

Inclusion Criteria:

1. Infertility and desire to conceive, justifying ART treatment,

2. Age between 18 and 36 years, inclusive, at time of informed consent,

3. Body mass index 18 to 30 kg/m2, inclusive,

4. Regular spontaneous menstrual cycles of 21 to 35 days,

5. Presence of both ovaries,

6. Transvaginal ultrasound scan (US) within 6 weeks and hysterosalpingogram, hysterosonogram or hysteroscopy within 2 years prior to beginning OCP treatment, showing no clinically significant uterine abnormality, which, in the Investigator's opinion, could impair embryo implantation or pregnancy continuation,

7. Normal early follicular phase (Day 2-4) serum FSH level, according to the local laboratory,

8. Normal serum TSH level, according to the local laboratory, Note: Subjects with low TSH levels who receive replacement therapy can be enrolled at the discretion of the investigator if local laboratory results (T4) demonstrate satisfactory thyroid function.

9. PAP smear test without clinically significant abnormalities within the last 6 months prior to beginning oral contraceptive therapy,

10. Negative pregnancy test prior to beginning GnRH-agonist therapy,

11. Male partner with semen analysis which is at least adequate for ICSI within last 6 months prior to beginning GnRH agonist therapy, according to local laboratory, Note: Donor sperm is not allowed.

12. Willing and able to comply with the protocol,

13. Voluntary provision of written informed consent, prior to any study related procedure that was not part of normal medical care, with the understanding that the subject can withdraw consent at any time without prejudice to her future medical care, and

14. Willingness to provide follow-up information on babies born as part of this study.

Exclusion Criteria:

1. Subject would require a starting dose of FSH > 150 IU/day, in the opinion of the Investigator,

2. Screening ultrasound demonstrating more than 12 follicles < 11 mm mean diameter in either ovary,

3. Two or more previous ART cycles (consecutive or not) with poor response to gonadotrophin, defined as £ 3 oocytes retrieved,

4. Three or more previous consecutive ART cycles without a biochemical or clinical pregnancy,

5. Previous failure of fertilization with ICSI,

6. A previous ART attempt in which there were no adequate or motile sperm before or after the processing of ejaculated sperm Note: epididymal or testicular spermatozoa is not allowed for this study,

7. Previous severe ovarian hyperstimulation syndrome (OHSS),

8. History or presence of tumors of the hypothalamus or pituitary gland,

9. History or presence of ovarian, uterine or mammary cancer,

10. History or presence of ovarian enlargement or cyst of unknown etiology,

11. Presence of endometriosis grade III - IV,

12. Presence of uni- or bilateral hydrosalpinx,

13. Abnormal gynecological bleeding of undetermined origin,

14. Contraindication to being pregnant and/or carrying a pregnancy to term,

15. History of ³ 3 clinical or preclinical (absence of gestational sac) miscarriages due to any cause,

16. Extra-uterine pregnancy within the 3 months prior to randomization,

17. Clinically significant systemic disease,

18. Known infection with human immunodeficiency virus (HIV), hepatitis B or C virus in the female or male partner,

19. Known allergy or hypersensitivity to human gonadotrophin preparations or to compounds that are structurally similar to any of the other medications administered during the study,

20. Any medical condition, which in the judgment of the Investigator may interfere with the absorption, distribution, metabolism or excretion of r- hFSH

21. Any active substance abuse or history of drug, medication or alcohol abuse within 5 years before screening,

22. ART cycle and/or ovarian stimulation within 30 days prior to informed consent,

23. Entered previously into this study or simultaneous participation in another clinical trial,

24. Subject is a smoker consuming more than 5 cigarettes per day

Local US Medical Information Office, Rockland, Massachusetts 02370, United States

Starting date: July 2007
Last updated: May 22, 2008