Clinical trial NCT04549116: Subcutaneous Progesterone in Frozen- Thawed Single Euploid Blastocyst Transfer.
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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Infertility
Keywords: Frozen embryo transfer
Lead sponsor: IBSA Institut Biochimique SA
Sponsor class: INDUSTRY
First posted: 2020-09-16
Enrollment: 680
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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-

Primary outcomes:
measure: Clinical pregnancy rate
timeFrame: 5 weeks post-embryo transfer
measure: Ongoing pregnancy
timeFrame: 10 weeks post-embryo transfer
Secondary outcomes:
measure: Positive pregnancy rate
timeFrame: 10+/-2 days after embryo transfer.
measure: Implantation rate
timeFrame: 6 weeks after embryo transfer,
measure: Delivery rate
timeFrame: 2-4 weeks post expected delivery date.
measure: Live birth rate
timeFrame: 2-4 weeks post expected delivery date.
measure: Cycle cancellation rate (with reason)
timeFrame: from treatment start until 10 weeks of pregnancy
measure: Adverse Events related to the mother
timeFrame: from Informed consent signature until 2-4 week after delivery.
measure: Local tolerability
timeFrame: from the 4th day of treatment administration until 10 weeks post embryo transfer.
measure: Early Miscarriage rate
timeFrame: from 5 weeks post embryo transfer until the 12th week of pregnancy.
measure: Late miscarriage rate
timeFrame: after the 12th week of pregnancy until delivery.
measure: Ectopic pregnancy rate
timeFrame: from 5 weeks post embryo transfer until the 12th week of pregnancy.
measure: Adverse events related to the newborn.
timeFrame: 2-4 weeks after expected delivery.
Other outcomes:
measure: Progesterone Pharmacokinetic (PK) characterization
timeFrame: 4 days after treatment start.
Locations:
city: Tempe
country: United States
facility: The Fertility Treatment Center, LLC
state: Arizona
city: Encino
country: United States
facility: HRC Fertility
state: California
city: Los Angeles
country: United States
facility: Kindbody
state: California
city: San Diego
country: United States
facility: San Diego Fertility
state: California
city: San Francisco
country: United States
facility: Spring Fertility
state: California
city: Norwalk
country: United States
facility: Illume Fertility
state: Connecticut
city: Newark
country: United States
facility: Reproductive Associates of Delaware
state: Delaware
city: Clearwater
country: United States
facility: Women's Medical Research Group, LLC
state: Florida
city: Margate
country: United States
facility: IVF Florida Reproductive Associates
state: Florida
city: Winter Park
country: United States
facility: The IVF Center
state: Florida
city: Hoffman Estates
country: United States
facility: InVia Fertility Specialists, PLLP
state: Illinois
city: Hasbrouck Heights
country: United States
facility: University Reproductive Associates, PC
state: New Jersey
city: Charlotte
country: United States
facility: Reproductive Endocrinology Associates of Charlotte
state: North Carolina
city: Raleigh
country: United States
facility: Carolina Conceptions
state: North Carolina
city: Cincinnati
country: United States
facility: Institute for Reproductive Health
state: Ohio
city: Bryn Mawr
country: United States
facility: Main Line Fertility
state: Pennsylvania
city: Chesterbrook
country: United States
facility: Shady Grove Fertility
state: Pennsylvania
city: Bedford
country: United States
facility: Care Fertility
state: Texas
city: Houston
country: United States
facility: Aspire Houston Fertility Institute
state: Texas
city: Webster
country: United States
facility: Center of Reproductive Medicine, LLC., Shady Grove Fertility
state: Texas
city: Pleasant Grove
country: United States
facility: Utah Fertility Center, PC
state: Utah
Study officials:
References: