An Observational Study of Follitropin Alpha Biosimilar: the Real-world Data

IVF Clinical Trial

Official title:

An Observational Study "FOLLITROPIN" Comparing the Efficacy of Follitropin Alpha Biosimilar: the Real-world Data

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04854707
• Other study ID #: IVF-2020
• Status: Completed
• Start date: January 12, 2020
• Est. completion date: January 20, 2021

Study information

• Verified date: September 2021
• Source: IVFarma LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Aim to investigate the efficacy of follitropin alpha biosimilar therapy (Primapur®) in nonselected real-world population.

Description:

A retrospective observational anonymized cohort study of follitropin alpha biosimilar (Primapur®) as a pre-filled pen injector with a dose adjustment of 5 IU, aimed to investigate its efficacy and safety in a nonselected population with indications to assisted reproductive technologies (ART) was carried out. The ovarian stimulation (OS) protocols included:

monotherapy protocols with using only Primapur®; mixed protocols (recombinant and urinary-derived gonadotropins); short protocols with using antagonists of gonadotropin-releasing hormone (GnRH) and long protocols with GnRH agonists. The stimulation protocols were analyzed with Primapur® application for at least 5 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5484
• Est. completion date: January 20, 2021
• Est. primary completion date: December 20, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 43 Years

Eligibility

Inclusion Criteria:

• Women with established causes of infertility and indications for the use of ART methods, according to the Order of the Ministry of Health of the Russian Federation "On the use of assisted reproductive technologies, contraindications and limitations to their use" No. 107 n dated August 30, 2012.

• Infertility due to female and/or male factor.

• Presence of ovaries accessible for aspiration of follicles.

• Anatomical and functional capability of uterus to bear pregnancy.

Exclusion Criteria:

• Women with established contraindications to the use of ART methods, according to the Order of the Ministry of Health of the Russian Federation "On the use of assisted reproductive technologies, contraindications and limitations to their use" No. 107 n dated August 30, 2012.

• Presence of pregnancy

• Hypersensitivity to follitropin alfa or excipients.

• Ovarian cysts (not associated with polycystic ovarian syndrome), uterine hemorrhage of unclear etiology

• Premature ovarian failure

• Presence of clinically significant systemic disease

• Presence of chronic cardiovascular, hepatic, renal or pulmonary disease

• Neoplasia

• Narcomania, alcoholism

Related Conditions & MeSH terms

• Disease
• Fertility Disorders
• Fertility Issues
• Gynecologic Disease
• Infertility
• IVF
• Reproductive Disorder
• Reproductive Issues

Intervention

Drug:
• Follitropin Alfa
Subcutaneous injection of follitropin alpha biosimilar only, with daily dose 100-300 IU for 10 days, maximum of 15 days, using antagonists of GnRH or agonist of GnRH.
• Follicle Stimulating Hormone/Luteinizing Hormone
Subcutaneous injection of follitropin alpha biosimilar, with daily dose 100-300 IU for at least 5 days, than added another gonadotropin for a maximum of 10 days, using antagonists of GnRH or agonist of GnRH.
• Follitropin Alfa
Subcutaneous injection of follitropin alpha biosimilar only, with daily dose 100-300 IU for 10 days, maximum of 15 days, using antagonists of GnRH only for suppression.
• Follitropin Alfa
Subcutaneous injection of follitropin alpha biosimilar only, with daily dose 100-300 IU for 10 days, maximum of 15 days, using agonists of GnRH only for suppression.
• Follicle Stimulating Hormone/Luteinizing Hormone
Overall ovarian stimulation protocols with follitropin alpha biosimilar for at least 5 days+other recombinant and menotropins and short (antagonists of GnRH) or long protocol (agonist of GnRH).

Locations

Country	Name	City	State
Russian Federation	Center for reproductive medicine, Barnaul	Barnaul
Russian Federation	Clinical Institute of Reproductive Medicine	Ekaterinburg
Russian Federation	Center for reproductive medicine, Irkutsk	Irkutsk
Russian Federation	Clinic "Mother and Child" Kazan	Kazan
Russian Federation	Clinic "Mother and Child" Kostroma	Kostroma
Russian Federation	Clinic "Mother and Child" Krasnodar	Krasnodar
Russian Federation	Center for reproductive medicine, Krasnoyarsk	Krasnoyarsk
Russian Federation	AltraVita IVF clinic	Moscow
Russian Federation	Center of Reproductive Medicine and Genetics "Nova Clinic"	Moscow
Russian Federation	Clinic "Mather and Child" Lefortovo	Moscow
Russian Federation	Clinic "Mather and Child" Savelovskaya	Moscow
Russian Federation	Clinic "Mother and Child" Khodynskoe Pole	Moscow
Russian Federation	Clinic "Mother and Child" Kuntsevo	Moscow
Russian Federation	Clinic "Mother and Child" South-West	Moscow
Russian Federation	Clinical Hospital MD GROUP (Perinatal Center on Sevastopolskiy)	Moscow
Russian Federation	Clinical Hospital Lapino	Moscow Oblast
Russian Federation	Clinic "Mother and Child"	Nizhny Novgorod
Russian Federation	Medika-2	Novokuznetsk
Russian Federation	Center for reproductive medicine, Novosibirsk	Novosibirsk
Russian Federation	Clinical Hospital "Avicenna"	Novosibirsk
Russian Federation	Ceter for reproductive medicine, Omsk	Omsk
Russian Federation	Clinic "Mother and Child" Perm	Perm
Russian Federation	Clinic "Mother and Child" Rostov-on-Don	Rostov-on-Don
Russian Federation	Clinic "Mather and Child"	Ryazan'
Russian Federation	"Genesis" Reproduction Centre	Saint Petersburg
Russian Federation	Clinic "Mother and Child" Saint-Petersburg	Saint Petersburg
Russian Federation	Clinical Hospital "Mother and Child"	Samara
Russian Federation	Clinic "Mather and Child" Tula	Tula
Russian Federation	Clinical Hospital "Mother and Child"	Tyumen
Russian Federation	Clinical Hospital "Mother and Child"	Ufa
Russian Federation	Clinic "Mother and Child" Vladimir	Vladimir
Russian Federation	Clinic "Mather and Child" Vladivostok	Vladivostok
Russian Federation	Clinic "Mother and Child" Volgograd	Volgograd
Russian Federation	Clinic "Mother and Child" Voronezh	Voronezh
Russian Federation	Clinic "Mother and Child" Yaroslavl	Yaroslavl

Sponsors (2)

Lead Sponsor	Collaborator
IVFarma LLC	Institute for Preventive and Social Medicine

Country where clinical trial is conducted

Russian Federation, 

References & Publications (2)

Kamilova D.P., Ovchinnikova M.M., Ablyaeva E.S., Leviashvili M.M., Stuleva N.S., Broitman E.V., Ganikhina M.A., Mayasina E.N., Iskhakova L.F., Boyarskiy K.Yu., Ovsyannikova E.N., Barakhoeva Z.B., Nikitin S.V., Bendusov I.A., Fetisova Yu.A., Yudina M.A., T

M Polzikov, D Kamilova, M Ovchinnikova, E Mayasina, K Boyarsky, S Nikitin, I Bendusov, M Ganikhina, Z Barakhoeva, E Osina, E Ablyaeva, D Khetagurova, T Ushakova, D Blinov, P-669 "Follitropin": A retrospective, observational study comparing the efficacy of

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Oocytes Retrieved	The total number of retrieved oocytes at the day of ovum pick-up. No more than 37 hours from the introduction of the ovulation inducer (HCG or GnRH-agonist).; Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646).	From date of start of ovarian stimulation with follitropin alpha up to 15 days
Primary	Percentage of Participants With Ongoing Clinical Pregnancy Per Embryo Transfer	Ongoing clinical pregnancy per embryo transfer (detection of gestational sac and heartbeat from 6 weeks after transfer), n (ongoing pregnancy rate per transfer with known outcome, %).; Due to delayed embryo transfers, the analysed population for "Ongoing clinical pregnancy per embryo transfer" was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2007 embryo transfers (1542 with known outcome); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2213 embryo transfers (1800 with known outcome); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 1809 embryo transfers (1466 with known outcome) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 404 embryo transfers (334 with known outcome).	At least 6 weeks after embryo transfer
Secondary	Number of Mature Oocytes	Mature oocytes (MII stage of development).; Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646).	From date of start of ovarian stimulation with follitropin alpha up to 15 days
Secondary	Number of Fertilized Oocytes	Fertilization rate (FR) is percentage of transformation of oocytes into two pronuclei (presence of two pronuclei: zygotes with 2PN).; Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646).	From date of start of ovarian stimulation with follitropin alpha up to 16 days
Secondary	Total Dose of Follitropin Alpha Biosimilar Protocol, IU	Mean dose of follitropin alpha biosimilar for ovarian stimulation.; Due to lack of efficacy of the therapy (ovarian stimulation was not completed and oocytes were not retrieved) the analysed population was: (1) Mixed protocols: recombinant and urinary-derived gonadotropins and antagonists/agonists of GnRH - 2625 participants (lack of efficacy: 78 participants, the analysed population was 2547 participants); (2) Monoprotocols: follitropin alpha biosimilar only and antagonists/agonists of GnRH - 2859 participants (lack of efficacy: 89, the analysed population was 2770); (3) Monoprotocols: follitropin alpha biosimilar only and antagonists of GnRH - 2183 participants (lack of efficacy: 59, the analysed population was 2124) and (4) Monoprotocols: follitropin alpha biosimilar only and agonist of GnRH - 676 participants (lack of efficacy: 30, the analysed population was 646).	From date of start of ovarian stimulation with follitropin alpha up to 16 days