Follitropin Delta in Long GnRH Agonist and GnRH Antagonist Protocols (BEYOND) (BEYOND)
Primary Purpose
Infertility, Female
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
FE 999049 + GnRH agonist (GONAPEPTYL)
FE 999049 + GnRH antagonist (CETROTIDE)
Sponsored by
About this trial
This is an interventional treatment trial for Infertility, Female
Eligibility Criteria
Inclusion Criteria:
- Infertile women aged 18-40 undergoing their first IVF/ICSI cycle that are in good physical and mental health and that have been diagnosed with problems in the fallopian tubes, mild endometriosis or have partners with decreased sperm quality.
- The participants must have a regular menstrual cycle, a normal uterus and 2 normal ovaries.
- The allowed body mass index is 17.5-32 Kg/m^2.
Exclusion Criteria:
- Women with very high ovarian reserve, strong preference for either treatment, severe endometriosis, history of repeated miscarriage, couples with known problems in the chromosomes, history or high risk of producing blood cloths, women known to have chronic diseases, women recently participating in trials with non-registered drugs.
Sites / Locations
- Das Kinderwunsch Institut Schenk GmbH
- Kepler University Hospital Linz
- Kinderwunschzentrum Goldenes Kreuz Privatklinik
- Rigshospitalet
- Hillel Yafe Medical Center
- Shaare Zedek Medical Center
- Beilinson Hospital Rabin Medical Center
- Sourasky Medical Center
- Dipartimento della Donna, del bambino e delle malattie urologiche
- European Hospital
- St. Elisabeth Ziekenhuis
- Isala Fertility Center
- Oslo University Hospital
- Sykehuset Telemark HF
- Medicus AS
- Gyn-A.R.T. AG
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
FE 999049 + GnRH agonist (GONAPEPTYL)
FE 999049 + GnRH antagonist (CETROTIDE)
Arm Description
Outcomes
Primary Outcome Measures
Number of oocytes retrieved
Secondary Outcome Measures
Proportion of subjects with cycle cancellation due to poor ovarian response or excessive ovarian response
For each subject, the reason for cycle cancellation will be recorded
Proportion of subjects with blastocyst transfer cancellation after oocyte retrieval due to (risk of) ovarian hyperstimulation syndrome (OHSS)
For each subject, the reason for blastocyst transfer cancellation will be recorded
Number of follicles
The total number of follicles and the number of follicles per size category will be reported
Proportion of subjects with <4, 4-7, 8-14, 15-19 and ≥20 oocytes retrieved
Grouped according to number of oocytes
Number of metaphase II oocytes
Only applicable for those inseminated using ICSI
Fertilization rate
Measured by the number of pronuclei. Fertilized oocytes with 2 pronuclei will be regarded as correctly fertilized
Number of embryos
The number of embryos (total and good-quality) will be reported. Embryo quality is determined by combined assesment of cleavage stage (number of blastomeres/compaction status) and embryo morphology parameters
Number of blastocysts
The number of blastocysts (total and good-quality) will be reported. Blastocyst quality is assessed by blastocyst expansion and hatching status, blastocyst inner cell mass grading, and trophectoderm grading. The scoring is based on the classification system by Gardner and Schoolcraft, with additional categories for inner cell mass (degenerative or no inner cell mass) and trophectoderm (degenerative or very large cells)
Circulating concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone and inhibin B
Total gonadotropin dose
Calculated by start dates, end dates and daily dose of investigational medicinal product
Number of stimulation days
Calculated by start dates and end dates
Positive beta human chorionic gonadotropin (βhCG) rate
Defined as positive serum βhCG test
Implantation rate
Defined as the number of gestational sacs after transfer divided by number of blastocysts transferred
Clinical pregnancy rate
Defined as at least one gestational sac
Vital pregnancy rate
Defined as at least one intrauterine gestational sac with fetal heart beat
Ongoing pregnancy rate
At least one intrauterine viable fetus
Ongoing implantation rate
Defined as number of intrauterine viable fetuses divided by the number of blastocysts transferred
Proportion of subjects with early OHSS (including OHSS of moderate/severe grade)
Measured as mild, moderate or severe
Proportion of subjects with late OHSS (including OHSS of moderate/severe grade)
Measured as mild, moderate or severe
Frequency of adverse events
Any untoward medical occurrence
Intensity of adverse events
Categorized as mild, moderate or severe
Technical malfunctions of the pre-filled injection pen
Incidences of technical malfunctions of the pre-filled injection pen will be recorded
Full Information
NCT ID
NCT03809429
First Posted
January 7, 2019
Last Updated
September 28, 2022
Sponsor
Ferring Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT03809429
Brief Title
Follitropin Delta in Long GnRH Agonist and GnRH Antagonist Protocols (BEYOND)
Acronym
BEYOND
Official Title
A Randomised, Controlled, Open Label, Parallel Group, Multicentre Trial Comparing the Efficacy and Safety of Individualised FE 999049 (Follitropin Delta) Dosing, Using a Long GnRH Agonist Protocol and a GnRH Antagonist Protocol in Women Undergoing Controlled Ovarian Stimulation
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
April 29, 2019 (Actual)
Primary Completion Date
February 16, 2022 (Actual)
Study Completion Date
February 16, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ferring Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
To compare the efficacy and safety of FE 999049 (follitropin delta) and its personalized dosing algorithm in controlled ovarian stimulation for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) using a long gonadotropin-releasing hormone (GnRH) agonist protocol versus a short GnRH antagonist protocol.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility, Female
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
437 (Actual)
8. Arms, Groups, and Interventions
Arm Title
FE 999049 + GnRH agonist (GONAPEPTYL)
Arm Type
Experimental
Arm Title
FE 999049 + GnRH antagonist (CETROTIDE)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
FE 999049 + GnRH agonist (GONAPEPTYL)
Intervention Description
Pre-filled injection pen
Intervention Type
Drug
Intervention Name(s)
FE 999049 + GnRH antagonist (CETROTIDE)
Intervention Description
Powder and solvent for solution for injection
Primary Outcome Measure Information:
Title
Number of oocytes retrieved
Time Frame
On day of oocyte retrieval (up to 22 days after start of stimulation)
Secondary Outcome Measure Information:
Title
Proportion of subjects with cycle cancellation due to poor ovarian response or excessive ovarian response
Description
For each subject, the reason for cycle cancellation will be recorded
Time Frame
At end-of-stimulation (up to 20 days)
Title
Proportion of subjects with blastocyst transfer cancellation after oocyte retrieval due to (risk of) ovarian hyperstimulation syndrome (OHSS)
Description
For each subject, the reason for blastocyst transfer cancellation will be recorded
Time Frame
At end of transfer (up to 4 weeks)
Title
Number of follicles
Description
The total number of follicles and the number of follicles per size category will be reported
Time Frame
On stimulation day 6 and at end-of-stimulation (up to 20 days)
Title
Proportion of subjects with <4, 4-7, 8-14, 15-19 and ≥20 oocytes retrieved
Description
Grouped according to number of oocytes
Time Frame
On day of oocyte retrieval (up to 22 days after start of stimulation)
Title
Number of metaphase II oocytes
Description
Only applicable for those inseminated using ICSI
Time Frame
On day of oocyte retrieval (up to 22 days after start of stimulation)
Title
Fertilization rate
Description
Measured by the number of pronuclei. Fertilized oocytes with 2 pronuclei will be regarded as correctly fertilized
Time Frame
On day 1 after oocyte retrieval (up to 23 days after start of stimulation)
Title
Number of embryos
Description
The number of embryos (total and good-quality) will be reported. Embryo quality is determined by combined assesment of cleavage stage (number of blastomeres/compaction status) and embryo morphology parameters
Time Frame
On day 3 after oocyte retrieval (up to 25 days after start of stimulation)
Title
Number of blastocysts
Description
The number of blastocysts (total and good-quality) will be reported. Blastocyst quality is assessed by blastocyst expansion and hatching status, blastocyst inner cell mass grading, and trophectoderm grading. The scoring is based on the classification system by Gardner and Schoolcraft, with additional categories for inner cell mass (degenerative or no inner cell mass) and trophectoderm (degenerative or very large cells)
Time Frame
On day 5 after oocyte retrieval (up to 27 days after start of stimulation)
Title
Circulating concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone and inhibin B
Time Frame
On stimulation day 6, at end-of-stimulation (up to 20 days after start of stimulation) and at oocyte retrieval (up to 22 days after start of stimulation)
Title
Total gonadotropin dose
Description
Calculated by start dates, end dates and daily dose of investigational medicinal product
Time Frame
Up to 20 days
Title
Number of stimulation days
Description
Calculated by start dates and end dates
Time Frame
Up to 20 days
Title
Positive beta human chorionic gonadotropin (βhCG) rate
Description
Defined as positive serum βhCG test
Time Frame
13-15 days after transfer (up to approximately 1.5 months after start of stimulation)
Title
Implantation rate
Description
Defined as the number of gestational sacs after transfer divided by number of blastocysts transferred
Time Frame
5-6 weeks after transfer (up to approximately 2.5 months after start of stimulation)
Title
Clinical pregnancy rate
Description
Defined as at least one gestational sac
Time Frame
5-6 weeks after transfer (up to approximately 2.5 months after start of stimulation)
Title
Vital pregnancy rate
Description
Defined as at least one intrauterine gestational sac with fetal heart beat
Time Frame
5-6 weeks after transfer (up to approximately 2.5 months after start of stimulation)
Title
Ongoing pregnancy rate
Description
At least one intrauterine viable fetus
Time Frame
10-11 weeks after transfer (up to approximately 4 months after start of stimulation)
Title
Ongoing implantation rate
Description
Defined as number of intrauterine viable fetuses divided by the number of blastocysts transferred
Time Frame
10-11 weeks after transfer (up to approximately 4 months after start of stimulation)
Title
Proportion of subjects with early OHSS (including OHSS of moderate/severe grade)
Description
Measured as mild, moderate or severe
Time Frame
Up to 9 days after triggering of final follicular maturation
Title
Proportion of subjects with late OHSS (including OHSS of moderate/severe grade)
Description
Measured as mild, moderate or severe
Time Frame
>9 days after triggering of final follicular maturation
Title
Frequency of adverse events
Description
Any untoward medical occurrence
Time Frame
From time of signing informed consent until the end-of-trial (approximately 7 months)
Title
Intensity of adverse events
Description
Categorized as mild, moderate or severe
Time Frame
From time of signing informed consent until the end-of-trial (approximately 7 months)
Title
Technical malfunctions of the pre-filled injection pen
Description
Incidences of technical malfunctions of the pre-filled injection pen will be recorded
Time Frame
Up to 20 days
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
Women undergoing their first IVF/ICSI cycle and aged 18-40 years will be included.
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Infertile women aged 18-40 undergoing their first IVF/ICSI cycle that are in good physical and mental health and that have been diagnosed with problems in the fallopian tubes, mild endometriosis or have partners with decreased sperm quality.
The participants must have a regular menstrual cycle, a normal uterus and 2 normal ovaries.
The allowed body mass index is 17.5-32 Kg/m^2.
Exclusion Criteria:
Women with very high ovarian reserve, strong preference for either treatment, severe endometriosis, history of repeated miscarriage, couples with known problems in the chromosomes, history or high risk of producing blood cloths, women known to have chronic diseases, women recently participating in trials with non-registered drugs.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Compliance
Organizational Affiliation
Ferring Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Das Kinderwunsch Institut Schenk GmbH
City
Dobl
Country
Austria
Facility Name
Kepler University Hospital Linz
City
Linz
Country
Austria
Facility Name
Kinderwunschzentrum Goldenes Kreuz Privatklinik
City
Vienna
Country
Austria
Facility Name
Rigshospitalet
City
Copenhagen
Country
Denmark
Facility Name
Hillel Yafe Medical Center
City
Hadera
Country
Israel
Facility Name
Shaare Zedek Medical Center
City
Jerusalem
Country
Israel
Facility Name
Beilinson Hospital Rabin Medical Center
City
Petah tikva
Country
Israel
Facility Name
Sourasky Medical Center
City
Tel Aviv
Country
Israel
Facility Name
Dipartimento della Donna, del bambino e delle malattie urologiche
City
Bologna
Country
Italy
Facility Name
European Hospital
City
Roma
Country
Italy
Facility Name
St. Elisabeth Ziekenhuis
City
Tilburg
Country
Netherlands
Facility Name
Isala Fertility Center
City
Zwolle
Country
Netherlands
Facility Name
Oslo University Hospital
City
Oslo
Country
Norway
Facility Name
Sykehuset Telemark HF
City
Porsgrunn
Country
Norway
Facility Name
Medicus AS
City
Trondheim
Country
Norway
Facility Name
Gyn-A.R.T. AG
City
Zürich
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Follitropin Delta in Long GnRH Agonist and GnRH Antagonist Protocols (BEYOND)
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