Efficacy, safety and tolerability of XM17 compared to Gonal-f® in women undergoing assisted reproductive technologies

ISRCTN	ISRCTN74772901
DOI	https://doi.org/10.1186/ISRCTN74772901
Secondary identifying numbers	XM17-05

Submission date: 09/04/2010
Registration date: 18/05/2010
Last edited: 07/01/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Urological and Genital Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Not provided at time of registration

Contact information

Prof Paul Devroey
Scientific

UZ Brussels
Laarbeeklaan 101
Brussels
1090
Belgium

Study information

Study design	International multicentre prospective randomised controlled assessor-blind parallel-group phase III study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please contact the sponsor below to request a patient information sheet
Scientific title	Efficacy, safety and tolerability of XM17 compared to Gonal-f® in women undergoing assisted reproductive technologies: a multinational, multicentre, randomised, controlled, assessor-blind, parallel group phase III study including follow-up periods
Study hypothesis	The primary objective is to show equivalent efficacy of XM17 (human recombinant follicle-stimulating hormone) compared to Gonal-f® in infertile women undergoing assisted reproductive technologies (ART).
Ethics approval(s)	1. Hungary: National Institute of Pharmacy, 18/03/2010, ref: OGYI/684-6/2010 2. Poland: Bioethics Committee of the Regional Medical Council in Bialystok, 17/03/2010, ref: 22/2010/IV 3. Germany: Ethics Committee of the Faculty of Medicine at the University of Heidelberg, 21/04/2010, ref: AFmu-492/2009
Condition	Infertility
Intervention	After checking the suitability of the patient, the patients will be down-regulated with a gonadotropin releasing hormone agonist. After successful down-regulation the patients will be randomised to a treatment with 150 IU/d XM17 (human recombinant FSH) or 150 IU/d Gonal-f® (follitropin alpha). During the first 5 days the dose is fixed to 150 IU/d and thereafter the dose of follicle stimulating hormone (FSH) can be adapted. After successful ovarian stimulation human chorionic gonadotropin will be administered. The cumulus oocyte complexes will be retrieved. Embryo transfer will be performed. A pregnancy test will be done about 16 - 19 days after oocyte retrieval. Clinical pregnancy (foetal heart beat, gestational sacs) will be evaluated by ultrasound examination about 5 - 7 weeks after oocyte retrieval. Patients being pregnant will be followed up until they give birth (follow-up part A). Patients not being pregnant can be treated for a second or third cycle with XM17 as stimulating drug (follow-up part B).
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	XM17, Gonal-f®
Primary outcome measure	Number of cumulus oocyte complexes retrieved
Secondary outcome measures	Efficacy: 1. Total r-hFSH dose 2. Number of days of r-hFSH stimulation 3. Number of follicles, 17-ß estradiol serum concentration and endometrial thickness on stimulation Day 6 prior to dose adaptation and on the day of hCG injection 4. Cancellation rate 5. Oocyte maturity and quality 6. Fertilisation rate 7. Clinical pregnancy rate Safety: 8. Frequency of OHSS 9. Adverse events 10. Vital signs 11. Laboratory tests 12. Physical examination, body weight 13. 12-lead electrocardiogram (ECG) 14. Tolerability (overall and local) 15. Immunogenicity (anti-FSH antibody formation)
Overall study start date	19/03/2010
Overall study end date	30/09/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Female
Target number of participants	280 randomised patients (140 per treatment group)
Participant inclusion criteria	1. Infertile female patients of any racial origin undergoing superovulation for ART 2. Aged 18 - 37 years (inclusive) at the time of enrolment 3. Good physical and mental health 4. Regular menstrual cycles of 21 - 35 days and presumed to be ovulatory 5. Body mass index (BMI) between 18 - 29 kg/m^2 inclusive 6. Transvaginal ultrasound documenting the presence of both ovaries without abnormalities and normal adnexa within the last 6 months 7. Basal follicle stimulating hormone (FSH), estradiol, prolactin, thyroid stimulating hormone (TSH) within the normal reference ranges at enrolment 8. Normal or clinically insignificant haematology, clinical chemistry and urinalysis parameters 9. Negative cervical Pap test within the last 6 months prior to study entry 10. Negative pregnancy test prior to starting pituitary downregulation 11. Able to understand and follow instructions and able to participate in the study for the entire period 12. Signed and dated written informed consent
Participant exclusion criteria	1. More than two previously completed consecutive unsuccessful in-vitro fertilisation (IVF) cycles 2. Primary ovarian failure or women known as poor responders 3. More than three miscarriages 4. History of a severe ovarian hyperstimulation syndrome (OHSS) 5. Malformations of sexual organs incompatible with pregnancy 6. One or both ovaries inaccessible for oocyte retrieval 7. Ovarian enlargement or cyst of more than 2 cm 8. Hydrosalpinx that has not been surgically removed or ligated 9. Patient affected by pathologies associated with any contraindication of being pregnant 10. Gynaecological haemorrhages of unknown aetiology 11. Uncontrolled moderate arterial hypertension defined as systolic blood pressure greater than 160 mmHg and diastolic blood pressure greater than 100 mmHg 12. Any significant cardiovascular, pulmonary, neurologic, allergic, endocrine, hepatic, renal or systemic disease 13. Patient with insulin-dependent diabetes mellitus 14. History of coagulation disorders 15. Known positive test for human immunodeficiency virus (HIV) antibodies, hepatitis B or hepatitis C 16. Neoplasm (e.g. tumours of the ovary, breast, uterus, hypothalamus or pituitary gland) 17. History of chemo- or radio-therapy 18. Use of concomitant medications that might interfere with study evaluations (e.g., prostaglandin inhibitors, psychotropic agents) 19. Known allergy or hypersensitivity to recombinant FSH preparations or one of their excipients 20. History of drug or alcohol abuse (last 3 years), current or past (3 months) smoking habits of greater than 10 cigarettes per day 21. Pregnancy or lactation at enrolment 22. Administration of clomiphene or gonadotropins within 30 days prior to enrolment 23. Administration of investigational drugs within 90 days prior to enrolment
Recruitment start date	19/03/2010
Recruitment end date	30/09/2011

Locations

Countries of recruitment

Belgium
Czech Republic
Germany
Hungary
Poland
United Kingdom

Study participating centre

UZ Brussels

Brussels
1090
Belgium

Sponsor information

BioGeneriX AG (Germany)
Industry

Janderstrasse 3
Mannheim
68199
Germany

Phone	+49 (0)621 8755625
Email	beate.gertz@biogenerix.com
Website	http://www.biogenerix.com
"ROR"	https://ror.org/03xa4xh46

Funders

Funder type

Industry

BioGeneriX AG (Germany)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	06/01/2016		Yes	No

Editorial Notes

07/01/2016: Publication reference added.