A phase III, randomized, double-blind, active-controlled, non-inferiority clinical trial to investigate the efficacy and safety of a single injection of Org 36286 (corifollitropin alfa) to induce multifollicular development for controlled ovarian stimulation using daily recombinant FSH as a reference

Induction of multifollicular development in women undergoing conventional in
vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) commonly
rely on multiple injections of FSH preparations. Development of new treatment
regimens requiring fewer injections is considered an advancement. To this end
Org 36286 (corifollitropin alfa) was developed. Given the pharmacokinetic
profile, a single injection of Org 36286 results in sustained follicular
stimulation and may replace the first 7 injections of any FSH preparation in
controlled ovarian stimulation (COS) for assisted reproductive technology (ART).

The available pre-clinical and clinical data on Org 36286 show that the
compound has a prolonged half-life and a higher in vivo bioactivity as compared
to that of recombinant human FSH (follitropin beta). Efficacy of Org 36286 has
been investigated. The results of the dose-finding trial indicated a
significant dose-response relationship with respect to the number of
cumulus-oocyte-complexes retrieved.
To date, more than 400 subjects have been treated with Org 36286 in phase I and
II trials. It is concluded that in these trials, Org 36286 was safe and
well-tolerated.

38819:
To investigate the efficacy and safety of a single injection of Org 36286 to
induce multifollicular development for COS using daily recFSH as a reference.
38821:
To evaluate whether Org 36286 treatment for the induction of multifollicular
growth in women undergoing controlled ovarian stimulation (COS) is safe for
pregnant subjects and their offspring.
38831:
To collect the outcome of FTET cycles performed after embryos are cryopreserved
in trial 38819 in order to estimate the cumulative pregnancy rate for each
treatment group.

38819:
This is a randomized, double blind, active controlled, non-inferiority clinical
trial
38821:
pregnancy and neonatal follow-up protocol
38831:
FTET cycle outcome follow-up protocol

Investigational group:
-Org 36286: single SC injection of 150 µg (0.5 mL): day 1*
-placebo-recFSH (equivalent of 200 IU fixed dose) (daily): day 1 u/i day 7
-recFSH (max 200 IU)(daily from day 8)
-hCG (5.000 or 10.000 IU/USP Units): as soon as 3 follicles > or = 17mm


Reference group:
-placebo Org 36286; single SC injection of 150 µg (0.5 mL): day 1*
-recFSH (SC injection 200 IU fixed dose): day 1 u/i day 7
-recFSH (max 200 IU)(daily from day 8)
-hCG(5.000 or 10.000 IU/USP Units): as soon as 3 follicles > or = 17mm


Both groups:
-Ganirelix (0.25 mg) (SC injection): day 5 u/i day hCG
-micronized progesterone (at least 600 mg/day, vaginally or at least 50 mg/day,
intramuscularly (IM)): day OPU till 6 weeks or menses or up to negative
pregnancy test performed at least 14 days after embryo transfer.

* Stimulation day 1 is day 2 or 3 of menstrual cycle

Risks:
Headache, nausea and fatique have been reported during treatment with Org
36286, FSH preparations and GnRH analogues (other medication used during
infertility treatment). General risks associated with ovarian stimulation are
e.g. pelvic pain, overstimulation, multiple pregnancy, ectopic pregnancy, etc.

Benefits:
It is anticipated that Org 36286 may be beneficial in further reducing the
number of FSH injections for patients undergoing ovarian stimulation for IVF or
ICSI. Patients will be thoroughly monitored throughout the study.