Study to Compare Efficacy and Safety of Primapur and Gonal-f in Women for Assisted Reproductive Treatment
Primary Purpose
Infertility, Female
Status
Completed
Phase
Phase 3
Locations
Russian Federation
Study Type
Interventional
Intervention
Follitropin alfa (Gonal-f)
Follitropin alfa (Primapur)
Sponsored by
About this trial
This is an interventional treatment trial for Infertility, Female focused on measuring in vitro fertilization
Eligibility Criteria
Inclusion Criteria:
- Infertility due to tubal factor and/or male factor
- Age between 20 and 35 years with regular menstrual cycles of 21-35 days
- First or second cycle in the present series of ART
- BMI (body mass index) ≥ 18 ≤ 30 kg/m2
- Basal FSH (follicle stimulating hormone) < 10 IU/L (cycle day 2-5)
- E2 (estradiol) levels < 50pg/mL (cycle day 2)
- AMH (anti-mullerian hormone) ≥ 1.0 ng/ml
- Antral follicle ≥ 4 to ≤ 15 follicles (both ovaries)
- Presence of both ovaries and normal uterine cavity
- Informed consent
Exclusion Criteria:
- Presence of pregnancy
- Hypersensitivity to follitropin alfa
- Ovarian cysts
- History of ≥2 succeeding ART (assisted reproductive technology) cycles IVF (in vitro fertilization) and/or ICSI (Intracytoplasmic sperm injection) before the study cycle
- Previous history of severe ovarian hyperstimulation syndrome
- Presence of polycystic ovaries (PCO)
- Presence of endometriosis and hydrosalpinx
- Presence of uterine disorders
- History of poor (< 4 oocytes) or hyper (> 25 oocytes) responses to FSH treatment at dose 150 IU and GnRH-antagonist (gonadotropin-releasing hormone) protocol
- Premature ovarian failure
- Ectopic pregnancy (3 month before the study cycle)
- Presence of clinically significant systemic disease
- Presence of chronic cardiovascular, hepatic, renal or pulmonary disease
- Presence of endocrine disorder
- Neoplasia
- Male infertility without mobile spermatozoa in the ejaculate, that need MESA (Microsurgical epididymal sperm aspiration)/TESE (testicular sperm extraction)/TESA (testicular sperm aspiration)
- Smoking > 10 cigarettes/day
- Narcomania, alcoholism
- Planned PGS (preimplantation genetic screeneing) /PGD (preimplantation genetic diagnosis)
Sites / Locations
- Clinical Hospital Lapino
- AltraVita IVF clinic
- Perinatal Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Primapur (Follitropin alfa)
Gonal-f (Follitropin alfa)
Arm Description
Outcomes
Primary Outcome Measures
Oocytes (Intention-to-Treat, ITT)
The total number of retrieved oocytes at the day of ovum pick-up. No more than 37 hours from the introduction of the trigger of ovulation (hCG or GnRH-agonist). The equivalence in the number of retrieved oocytes was tested using a predetermined equivalence margin of +/- 3.4 oocytes.
Secondary Outcome Measures
Number of Follicles With Size ≥ 16 mm
The number of follicles 16 mm or over in diameter at the day of hCG (or GnRH-agonist) administration
Mature Oocytes
The number of mature oocytes (MII stage of development)
Fertilised Oocytes
The number of fertilised oocytes with the presence of two pronuclei: 2PN
Percentage of Patients With Embryo Transfer
The number of patients (and percentage) with embryo transfers on days 3 and 5 after ovum pick-up
Total Dose of Follitropin Alfa
The total dose of the follitropin alfa administrated during the ovarian hyperstimulation protocol (measured in International Units - IU)
Number of Days of Follitropin Alfa Treatment
The duration of ovarian hyperstimulation protocol (at the day of trigger of ovulation)
Number of Patients With Follitropin Alfa Dose Correction
The number of dose adjustments during the ovarian hyperstimulation protocol (increment 25-50 IU)
Number of Patients With Cycle Cancellation
The number of the ovarian hyperstimulation protocol cancellation (at the day of trigger of ovulation)
Number of No-responders
The number of patients with no response to follitropin alfa treatment (absence of growing follicles, no any oocytes obtained at the day of ovum pick-up)
Percentage of Patients With Serum hCG More Than 25 IU/l
Biochemical pregnancy test: serum hCG more than 25 IU/l (days 12-17 after embryo transfer)
Percentage of Patients With the Evidence for Clinical Pregnancy
Confirmation of clinical pregnancy: ultrasound detection of intrauterine gestational sac and heart activity
Full Information
NCT ID
NCT03088137
First Posted
March 2, 2017
Last Updated
March 22, 2022
Sponsor
IVFarma LLC
Collaborators
BridgePharm LLC, GlobalPharma LLC
1. Study Identification
Unique Protocol Identification Number
NCT03088137
Brief Title
Study to Compare Efficacy and Safety of Primapur and Gonal-f in Women for Assisted Reproductive Treatment
Official Title
Multicentre Study to Compare Efficacy and Safety of Primapur and Gonal-f in Women for Assisted Reproductive Treatment
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
February 8, 2017 (Actual)
Primary Completion Date
August 17, 2018 (Actual)
Study Completion Date
August 17, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
IVFarma LLC
Collaborators
BridgePharm LLC, GlobalPharma LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to show equivalence with regard to the number of oocytes retrieved between follitropin alfa (pen-injectors) Primapur® and Gonal-f® in woman undergoing IVF/ICSI
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility, Female
Keywords
in vitro fertilization
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
118 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Primapur (Follitropin alfa)
Arm Type
Experimental
Arm Title
Gonal-f (Follitropin alfa)
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Follitropin alfa (Gonal-f)
Intervention Description
Subcutaneous injection, fixed starting dose 150 IU for 5 days, maximum of 16 days of ovarian hyperstimulation
Intervention Type
Drug
Intervention Name(s)
Follitropin alfa (Primapur)
Intervention Description
Subcutaneous injection, fixed starting dose 150 IU for 5 days, maximum of 16 days of ovarian hyperstimulation
Primary Outcome Measure Information:
Title
Oocytes (Intention-to-Treat, ITT)
Description
The total number of retrieved oocytes at the day of ovum pick-up. No more than 37 hours from the introduction of the trigger of ovulation (hCG or GnRH-agonist). The equivalence in the number of retrieved oocytes was tested using a predetermined equivalence margin of +/- 3.4 oocytes.
Time Frame
From date of randomization up to 18 days
Secondary Outcome Measure Information:
Title
Number of Follicles With Size ≥ 16 mm
Description
The number of follicles 16 mm or over in diameter at the day of hCG (or GnRH-agonist) administration
Time Frame
From date of randomization up to 16 days
Title
Mature Oocytes
Description
The number of mature oocytes (MII stage of development)
Time Frame
From date of randomization up to 18 days
Title
Fertilised Oocytes
Description
The number of fertilised oocytes with the presence of two pronuclei: 2PN
Time Frame
From date of randomization up to 19 days
Title
Percentage of Patients With Embryo Transfer
Description
The number of patients (and percentage) with embryo transfers on days 3 and 5 after ovum pick-up
Time Frame
From date of randomization up to 25 days
Title
Total Dose of Follitropin Alfa
Description
The total dose of the follitropin alfa administrated during the ovarian hyperstimulation protocol (measured in International Units - IU)
Time Frame
From date of randomization up to 16 days
Title
Number of Days of Follitropin Alfa Treatment
Description
The duration of ovarian hyperstimulation protocol (at the day of trigger of ovulation)
Time Frame
From date of randomization up to 16 days
Title
Number of Patients With Follitropin Alfa Dose Correction
Description
The number of dose adjustments during the ovarian hyperstimulation protocol (increment 25-50 IU)
Time Frame
From date of randomization up to 16 days
Title
Number of Patients With Cycle Cancellation
Description
The number of the ovarian hyperstimulation protocol cancellation (at the day of trigger of ovulation)
Time Frame
From date of randomization up to 16 days
Title
Number of No-responders
Description
The number of patients with no response to follitropin alfa treatment (absence of growing follicles, no any oocytes obtained at the day of ovum pick-up)
Time Frame
From date of randomization up to 8 days
Title
Percentage of Patients With Serum hCG More Than 25 IU/l
Description
Biochemical pregnancy test: serum hCG more than 25 IU/l (days 12-17 after embryo transfer)
Time Frame
From date of randomization up to 42 days
Title
Percentage of Patients With the Evidence for Clinical Pregnancy
Description
Confirmation of clinical pregnancy: ultrasound detection of intrauterine gestational sac and heart activity
Time Frame
The 10th week after embryo transfer
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Infertility due to tubal factor and/or male factor
Age between 20 and 35 years with regular menstrual cycles of 21-35 days
First or second cycle in the present series of ART
BMI (body mass index) ≥ 18 ≤ 30 kg/m2
Basal FSH (follicle stimulating hormone) < 10 IU/L (cycle day 2-5)
E2 (estradiol) levels < 50pg/mL (cycle day 2)
AMH (anti-mullerian hormone) ≥ 1.0 ng/ml
Antral follicle ≥ 4 to ≤ 15 follicles (both ovaries)
Presence of both ovaries and normal uterine cavity
Informed consent
Exclusion Criteria:
Presence of pregnancy
Hypersensitivity to follitropin alfa
Ovarian cysts
History of ≥2 succeeding ART (assisted reproductive technology) cycles IVF (in vitro fertilization) and/or ICSI (Intracytoplasmic sperm injection) before the study cycle
Previous history of severe ovarian hyperstimulation syndrome
Presence of polycystic ovaries (PCO)
Presence of endometriosis and hydrosalpinx
Presence of uterine disorders
History of poor (< 4 oocytes) or hyper (> 25 oocytes) responses to FSH treatment at dose 150 IU and GnRH-antagonist (gonadotropin-releasing hormone) protocol
Premature ovarian failure
Ectopic pregnancy (3 month before the study cycle)
Presence of clinically significant systemic disease
Presence of chronic cardiovascular, hepatic, renal or pulmonary disease
Presence of endocrine disorder
Neoplasia
Male infertility without mobile spermatozoa in the ejaculate, that need MESA (Microsurgical epididymal sperm aspiration)/TESE (testicular sperm extraction)/TESA (testicular sperm aspiration)
Smoking > 10 cigarettes/day
Narcomania, alcoholism
Planned PGS (preimplantation genetic screeneing) /PGD (preimplantation genetic diagnosis)
Facility Information:
Facility Name
Clinical Hospital Lapino
City
Moscow Oblast
Country
Russian Federation
Facility Name
AltraVita IVF clinic
City
Moscow
Country
Russian Federation
Facility Name
Perinatal Medical Center
City
Moscow
Country
Russian Federation
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
Citation
M. Polzikov, Z. Barakhoeva, S. Yakovenko, M. Ovchinnikova, L.Vovk, Y. Fetisova. A multicenter, randomized study comparing the efficacy of follitropin alpha biosimilar and the original follitropin alpha. Abstracts of the 35th Annual Meeting of the ESHRE, Vienna, Austria 24 to 26 June 2019 (abstract P-649), Human Reproduction, 2019; Vol. 34, Suppl. 1, p. i439.
Results Reference
result
PubMed Identifier
31400644
Citation
Barakhoeva Z, Vovk L, Fetisova Y, Marilova N, Ovchinnikova M, Tischenko M, Scherbatyuk Y, Kolotovkina A, Miskun A, Kasyanova G, Teterina T, Zorina I, Belousova N, Morozova E, Yakovenko S, Apryshko V, Sichinava L, Shalinsmall a, Cyrillic R, Polzikov M. A multicenter, randomized, phase III study comparing the efficacy and safety of follitropin alpha biosimilar and the original follitropin alpha. Eur J Obstet Gynecol Reprod Biol. 2019 Oct;241:6-12. doi: 10.1016/j.ejogrb.2019.07.032. Epub 2019 Jul 26.
Results Reference
result
Citation
Barakhoeva Z.B., Vovk L.A., Zorina I.V., Belousova N.Y., Teterina T.A., Yakovenko S.A., Apryshko V.P., Fetisova Y.A., Marilova N.A., Morozova E.G., Ovchinnikova M.M., Tishenko M.A., Sherbatyuk Y.V., Kolotovkina A.V., Miskun A.A., Kasyanova G.V., Sichinava L.G., Shalinа R.I., Polzikov M.A. Major results of a phase III comparative multicenter study on the follitropin alfa biosimilar (Primapur®) and the original follitropin alfa (Gonal-f®). Akusherstvo, ginekologiya i reprodukciya. 2018;12(3):5-16. (In Russ.) https://doi.org/10.17749/2313-7347.2018.12.3.005-016
Results Reference
result
PubMed Identifier
35222266
Citation
Polzikov M, Blinov D, Barakhoeva Z, Vovk L, Fetisova Y, Ovchinnikova M, Tischenko M, Zorina I, Yurasov V, Ushakova T, Sergeyev O. Association of the Serum Folate and Total Calcium and Magnesium Levels Before Ovarian Stimulation With Outcomes of Fresh In Vitro Fertilization Cycles in Normogonadotropic Women. Front Endocrinol (Lausanne). 2022 Feb 11;13:732731. doi: 10.3389/fendo.2022.732731. eCollection 2022.
Results Reference
derived
Links:
URL
https://doi.org/10.1093/humrep/34.Supplement_1.1
Description
Abstracts of the 35th Annual Meeting of the ESHRE, Vienna, Austria 24 to 26 June 2019
URL
https://doi.org/10.1016/j.ejogrb.2019.07.032
Description
European Journal of Obstetrics & Gynecology and Reproductive Biology Volume 241, October 2019, Pages 6-12
Learn more about this trial
Study to Compare Efficacy and Safety of Primapur and Gonal-f in Women for Assisted Reproductive Treatment
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