Subcutaneous Progesterone in Frozen- Thawed Single Euploid Blastocyst Transfer.

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 Support in Modified Natural Frozen Euploid Blastocyst Transfer.

Sponsors

Lead Sponsor: IBSA Institut Biochimique SA

Source IBSA Institut Biochimique SA
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.

Overall Status Not yet recruiting
Start Date November 2020
Completion Date September 2022
Primary Completion Date March 2022
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Clinical pregnancy rate 5 weeks post-embryo transfer
Ongoing pregnancy 10 weeks post-embryo transfer
Secondary Outcome
Measure Time Frame
Positive pregnancy rate 10+/-2 days after embryo transfer.
Implantation rate 6 weeks after embryo transfer,
Delivery rate 2-4 weeks post expected delivery date.
Live birth rate 2-4 weeks post expected delivery date.
Cycle cancellation rate (with reason) from treatment start until 10 weeks of pregnancy
Adverse Events related to the mother from Informed consent signature until 2-4 week after delivery.
Local tolerability from the 4th day of treatment administration until 10 weeks post embryo transfer.
Early Miscarriage rate from 5 weeks post embryo transfer until the 12th week of pregnancy.
Late miscarriage rate after the 12th week of pregnancy until delivery.
Ectopic pregnancy rate from 5 weeks post embryo transfer until the 12th week of pregnancy.
Adverse events related to the newborn. 2-4 weeks after expected delivery.
Enrollment 600
Condition
Intervention

Intervention Type: Drug

Intervention Name: Progesterone-IBSA Injectable Solution

Description: Progesterone-IBSA 25mg, twice daily (BID) SC Injection every 12 hours

Arm Group Label: Investigational

Other Name: Prolutex

Intervention Type: Drug

Intervention Name: Progesterone Vaginal Gel with Applicator

Description: Crinone 8%, 90 mg, QD intravaginally

Arm Group Label: Comparator

Other Name: Crinone

Intervention Type: Drug

Intervention Name: Placebo Vaginal gel with applicator

Description: Vaginal gel Placebo, once daily (QD) intravaginally

Arm Group Label: Investigational

Intervention Type: Drug

Intervention Name: Placebo injectable solution

Description: Placebo injectable solution, BID SC Injection every 12 hours

Arm Group Label: Comparator

Eligibility

Criteria:

Inclusion Criteria:

- Both the female subject and their partner (if applicable) have 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, Estradiol (E2) <70 pg/mL and Anti Muellerian Hormone (AMH) >0.7 ng/mL (within 6 months from frozen embryo transfer [FET]);

- Semen used during IVF 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 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;

- Use of concomitant medications that might interfere with the study evaluation (Use of insulin sensitizing agents, lithium, vaginal medications/preparations, any drugs for luteal support other than those specified in the protocol, Aspirin, Any hormonal treatment within 1 month before the start of ovarian stimulation, with the exception of levothyroxine);

- Participation in a concurrent clinical trial or in another investigational drug trial within the past 2 months-

Gender: Female

Minimum Age: 35 Years

Maximum Age: 42 Years

Healthy Volunteers: No

Overall Contact

Last Name: Barbara PS Cometti, PhD

Phone: +41 58 360 10 00

Email: [email protected]

Verification Date

August 2020

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Investigational

Type: Experimental

Description: Progesterone-IBSA 25mg, twice daily (BID) subcutaneous (SC) injection every 12 hours and Crinone Placebo, once daily (QD) intravaginally.

Label: Comparator

Type: Active Comparator

Description: Crinone 8%, 90 mg, QD intravaginally and Progesterone-IBSA Placebo, BID SC Injection every 12 hours

Acronym PROGRESS
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description: Double-blind, double-dummy.

Source: ClinicalTrials.gov