Subcutaneous Progesterone in Frozen- Thawed Single Euploid Blastocyst Transfer.

Infertility Clinical Trial

— PROGRESS  

Official title:

A Multicenter, Randomized, Controlled, Double-blind, Double-dummy Study to Evaluate the Safety and Efficacy of Subcutaneous Progesterone Compared to Vaginal Progesterone for Luteal Phase Supplementation in Modified Natural Frozen Euploid Blastocyst Transfer.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04549116
• Other study ID #: 20US-Prg03
• Status: Recruiting
• Phase: Phase 3
• Start date: October 12, 2022
• Est. completion date: March 2025

Study information

• Verified date: March 2024
• Source: IBSA Institut Biochimique SA
• Contact: R&D Scientific Affairs
• Phone: +41 58 360 10 00
• Email: sd[@]ibsa.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority clinical study in women aged 35 to 42 years. This study will investigate the safety and efficacy of Progesterone-IBSA to support euploid embryo blastocyst implantation and early pregnancy after frozen embryo transfer (FET) in a modified natural cycle as a treatment for infertile women. Subjects will be randomized to receive either active Progesterone-IBSA or Crinone 8% for luteal and early pregnancy support and these two groups will be compared.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 680
• Est. completion date: March 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 35 Years to 42 Years

Eligibility

Inclusion Criteria:

• subject has given written informed consent;
• Premenopausal women 35 to 42 years of age at the time of consent (at least 35 [including day of birthday] and no more than 42 [up to the day before their 43rd birthday]);
• Valid indication for IVF treatment (i.e. history of infertility according to ASRM definition, single women or same-sex couples);
• Consistent, regular spontaneous ovulatory menstrual cycle with normal length (24-38 days included);
• Body mass index (BMI) < 38 kg/m2;
• Subject with at least one euploid frozen blastocyst from a previous IVF treatment cycle;
• Less than 3 previous consecutive euploid blastocyst transfers without a life birth;
• Baseline Follicle Stimulating Hormone (FSH) < 15 mIU/mL, and Anti Muellerian Hormone (AMH) >0.7 ng/mL (within 6 months from screening for subjects requiring a stimulation cycle to obtain a euploid embryo); and Estradiol (E2) < 90 pg/mL and Progesterone (P4)< 1.5 ng/mL at Visit 1 (for all subjects);
• Semen used during IVF(for subjects requiring a stimulation cycle to obtain a euploid embryo) was produced by ejaculation (not surgically derived sperm) from either the partner or from a sperm donor. Donor must be 18-40 years of age at the time of collection and compliant with 21 Code of Regulations (CFR) section 1271 Subpart C;
• Hysterosalpingography, hysteroscopy, 3D ultrasound or sonohysterogram documenting a normal uterine cavity within the last year;
• Normal cervical cytology/High Risk human papillomavirus (HPV) testing per American College of Obstetricians and Gynecologists guidelines.

Exclusion Criteria:

• Oligo or anovulation (spontaneous menses > 39 days apart);
• Breastfeeding or Pregnancy;
• Contraindication to pregnancy (i.e. an active, uncontrolled clinically significant medical condition or abnormality of the sexual organs determined by the provider);
• Known family history of major congenital anomalies;
• Moderate to severe current endometriosis (stage 3 or 4);
• Presence of a unilateral or bilateral hydrosalpinx that communicates with the uterus, that has not been ligated prior to treatment;
• Recurrent pregnancy loss (RPL) as defined by the American Society of Reproductive Medicine (ASRM) as two or more consecutive failed clinical pregnancies;
• Presence of a submucosal or intramural fibroid > 4 cm which distorts the uterine cavity or are > 5 cm in diameter;
• Untreated uterine pathology that could impair embryo implantation (i.e. scarring/Asherman's syndrome or intra uterine polyps > 1 cm in size);
• Type 1 or 2 diabetes mellitus based on American Diabetes Association (ADA) criteria3;
• Uncontrolled adrenal or thyroid dysfunction;
• History of conditions (i.e. toxic shock syndrome) that would contraindicate use of a vaginal progesterone product;
• Subjects with hepatic impairment (liver function tests > 2x upper limit of normal);
• Subjects with renal impairment (estimated creatinine clearance <60 mL/min/1.73 m2);
• History of an active or treated autoimmune disease (i.e. systemic lupus erythematosus);
• History of arterial disease (i.e. Prior or active thrombophlebitis, thromboembolic disorder or known thrombophilia);
• Neoplasias (current) or history of neoplasia that may be responsive to progesterone;
• High grade cervical dysplasia;
• Undiagnosed vaginal bleeding (i.e. at the time of screening);
• Use of donor eggs or plans to use a gestational carrier;
• Use of endometrial receptivity array (ERA) test to postpone or anticipate the embryo transfer (ET) day;
• Use of epididymal, testicular , electro-ejaculated or chemotherapy exposed sperm;
• Known allergy to progesterone preparations or their excipients;
• Current dependence on alcohol, tobacco (must not be smoking/using tobacco x 2 months before the study) or drugs or psychotropic medications labeled as Pregnancy Categories D and X;
• Use of concomitant medications within 1 month previous the start of the FET cycle preparation up to gestational week 12 that might interfere with the study evaluation (use of insulin sensitizing agents, vaginal medications/preparations, any drugs for luteal support other than those specified in the protocol, aspirin, any hormonal treatment, with the exception of levothyroxine);
• Participation in a concurrent clinical trial or in another investigational drug trial within the past 2 months-

Related Conditions & MeSH terms

• Infertility

Intervention

Drug:
• Progesterone-IBSA Injectable Solution
Progesterone-IBSA 25mg, twice daily (BID) SC Injection every 12 hours
• Progesterone Vaginal Gel with Applicator
Crinone 8%, 90 mg, QD intravaginally
• Placebo Vaginal gel with applicator
Vaginal gel Placebo, once daily (QD) intravaginally
• Placebo injectable solution
Placebo injectable solution, BID SC Injection every 12 hours

Locations

Country	Name	City	State
United States	Care Fertility	Bedford	Texas
United States	Main Line Fertility	Bryn Mawr	Pennsylvania
United States	Reproductive Endocrinology Associates of Charlotte	Charlotte	North Carolina
United States	Shady Grove Fertility	Chesterbrook	Pennsylvania
United States	Institute for Reproductive Health	Cincinnati	Ohio
United States	Women's Medical Research Group, LLC	Clearwater	Florida
United States	HRC Fertility	Encino	California
United States	University Reproductive Associates, PC	Hasbrouck Heights	New Jersey
United States	InVia Fertility Specialists, PLLP	Hoffman Estates	Illinois
United States	Aspire Houston Fertility Institute	Houston	Texas
United States	Kindbody	Los Angeles	California
United States	IVF Florida Reproductive Associates	Margate	Florida
United States	Reproductive Associates of Delaware	Newark	Delaware
United States	Illume Fertility	Norwalk	Connecticut
United States	Utah Fertility Center, PC	Pleasant Grove	Utah
United States	Carolina Conceptions	Raleigh	North Carolina
United States	San Diego Fertility	San Diego	California
United States	Spring Fertility	San Francisco	California
United States	The Fertility Treatment Center, LLC	Tempe	Arizona
United States	Center of Reproductive Medicine, LLC., Shady Grove Fertility	Webster	Texas
United States	The IVF Center	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
IBSA Institut Biochimique SA

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Progesterone Pharmacokinetic (PK) characterization	Blood sampling to assess Progesterone levels will be collected in order to characterize the PK profile at steady state in the target population	4 days after treatment start.
Primary	Clinical pregnancy rate	defined by the presence of an intrauterine fetal heart beat	5 weeks post-embryo transfer
Primary	Ongoing pregnancy	defined by the presence of an ongoing intrauterine pregnancy with fetal heart beat	10 weeks post-embryo transfer
Secondary	Positive pregnancy rate	positive serum ß-human chorionic gonadotropin (hCG) test rate	10+/-2 days after embryo transfer.
Secondary	Implantation rate	defined by the number of gestational sacs observed at Visit 6 by means of a transvaginal ultrasound (TVUS), divided by the number of blastocysts transferred (%)	6 weeks after embryo transfer,
Secondary	Delivery rate	defined as the number of deliveries with at least one live birth or stillbirth (%)	2-4 weeks post expected delivery date.
Secondary	Live birth rate	defined as the complete expulsion or extraction from a woman of a product of fertilization, after 22 completed weeks of gestational age; which, after such separation, breathes or shows any other evidence of life	2-4 weeks post expected delivery date.
Secondary	Cycle cancellation rate (with reason)	defined as number of subjects dropping form the study at any time.	from treatment start until 10 weeks of pregnancy
Secondary	Adverse Events related to the mother	frequency and severity of adverse events related to the mother.	from Informed consent signature until 2-4 week after delivery.
Secondary	Local tolerability	At each visit, the subject will be queried about the presence of local reactions at administration site (pain, redness, swelling and itching at injection site and pain, irritation, swelling and leakage in the genital area). Events will be described in term of nature, severity (mild, moderate, severe, or very severe) and duration (persisted for up to 1 hour, persisted for more than 1 up to 4 hours, persisted for more than 4 up to 12 hours, persisted for more than 12 hours).	from the 4th day of treatment administration until 10 weeks post embryo transfer.
Secondary	Early Miscarriage rate	defined as a spontaneous loss of an intra-uterine pregnancy	from 5 weeks post embryo transfer until the 12th week of pregnancy.
Secondary	Late miscarriage rate	defined as a spontaneous loss of an intra-uterine pregnancy	after the 12th week of pregnancy until delivery.
Secondary	Ectopic pregnancy rate	defined as a pregnancy outside the uterine cavity, diagnosed by ultrasound, surgical visualization or histopathology.	from 5 weeks post embryo transfer until the 12th week of pregnancy.
Secondary	Adverse events related to the newborn.	frequency and severity of adverse events related to the newborn.	2-4 weeks after expected delivery.