Subcutaneous Progesterone in Frozen- Thawed Single Euploid Blastocyst Transfer. (PROGRESS)

March 4, 2024 updated by: IBSA Institut Biochimique SA

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.

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.

Study Overview

Study Type

Interventional

Enrollment (Estimated)

680

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: R&D Scientific Affairs
  • Phone Number: +41 58 360 10 00
  • Email: sd@ibsa.ch

Study Locations

    • Arizona
      • Tempe, Arizona, United States, 85284
        • Recruiting
        • The Fertility Treatment Center, LLC
        • Contact:
          • Phone Number: 800-774-1534
    • California
      • Encino, California, United States, 91436
        • Recruiting
        • HRC Fertility
        • Contact:
          • Phone Number: 818-788-7288
      • Los Angeles, California, United States, 90067
        • Recruiting
        • Kindbody
        • Contact:
          • Phone Number: 650-445-4724
      • San Diego, California, United States, 92130
        • Recruiting
        • San Diego Fertility
        • Contact:
          • Phone Number: 858-794-6363
      • San Francisco, California, United States, 94109
        • Terminated
        • Spring Fertility
    • Connecticut
      • Norwalk, Connecticut, United States, 06851
        • Recruiting
        • Illume Fertility
        • Contact:
          • Phone Number: 203-750-7400
    • Delaware
      • Newark, Delaware, United States, 19713
        • Recruiting
        • Reproductive Associates of Delaware
        • Contact:
          • Phone Number: 302-602-8852
    • Florida
      • Clearwater, Florida, United States, 33759
        • Recruiting
        • Women's Medical Research Group, LLC
        • Contact:
          • Phone Number: 727-724-9730
      • Margate, Florida, United States, 33063
        • Recruiting
        • IVF Florida Reproductive Associates
        • Contact:
          • Phone Number: 954-247-6200
      • Winter Park, Florida, United States, 32792
        • Recruiting
        • The IVF Center
        • Contact:
          • Phone Number: 407-672-1106
    • Illinois
      • Hoffman Estates, Illinois, United States, 60169
        • Recruiting
        • InVia Fertility Specialists, PLLP
        • Contact:
          • Phone Number: 847-884-8884
    • New Jersey
      • Hasbrouck Heights, New Jersey, United States, 07604
        • Recruiting
        • University Reproductive Associates, PC
        • Contact:
          • Phone Number: 201-288-6330
    • North Carolina
      • Charlotte, North Carolina, United States, 28207
        • Recruiting
        • Reproductive Endocrinology Associates of Charlotte
        • Contact:
          • Phone Number: 704-343-4455
      • Raleigh, North Carolina, United States, 27607
        • Recruiting
        • Carolina Conceptions
        • Contact:
          • Phone Number: 919-782-5911
    • Ohio
      • Cincinnati, Ohio, United States, 45209
        • Recruiting
        • Institute for Reproductive Health
        • Contact:
          • Phone Number: 513-924-5554
    • Pennsylvania
      • Bryn Mawr, Pennsylvania, United States, 19010
        • Recruiting
        • Main Line Fertility
        • Contact:
          • Phone Number: 484-380-4861
      • Chesterbrook, Pennsylvania, United States, 19087
        • Recruiting
        • Shady Grove Fertility
        • Contact:
          • Phone Number: 301-545-1289
    • Texas
      • Bedford, Texas, United States, 76022
        • Recruiting
        • Care Fertility
        • Contact:
          • Phone Number: 817-540-7072
      • Houston, Texas, United States, 77063
        • Terminated
        • Aspire Houston Fertility Institute
      • Webster, Texas, United States, 77598
        • Recruiting
        • Center of Reproductive Medicine, LLC., Shady Grove Fertility
        • Contact:
          • Phone Number: 281-332-0073
    • Utah
      • Pleasant Grove, Utah, United States, 84062
        • Recruiting
        • Utah Fertility Center, PC
        • Contact:
          • Phone Number: 801-785-5100

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

33 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Description

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-

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Investigational
Progesterone-IBSA 25mg, twice daily (BID) subcutaneous (SC) injection every 12 hours and Crinone Placebo, once daily (QD) intravaginally.
Progesterone-IBSA 25mg, twice daily (BID) SC Injection every 12 hours
Other Names:
  • Prolutex
Vaginal gel Placebo, once daily (QD) intravaginally
Active Comparator: Comparator
Crinone 8%, 90 mg, QD intravaginally and Progesterone-IBSA Placebo, BID SC Injection every 12 hours
Crinone 8%, 90 mg, QD intravaginally
Other Names:
  • Crinone
Placebo injectable solution, BID SC Injection every 12 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical pregnancy rate
Time Frame: 5 weeks post-embryo transfer
defined by the presence of an intrauterine fetal heart beat
5 weeks post-embryo transfer
Ongoing pregnancy
Time Frame: 10 weeks post-embryo transfer
defined by the presence of an ongoing intrauterine pregnancy with fetal heart beat
10 weeks post-embryo transfer

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Positive pregnancy rate
Time Frame: 10+/-2 days after embryo transfer.
positive serum β-human chorionic gonadotropin (hCG) test rate
10+/-2 days after embryo transfer.
Implantation rate
Time Frame: 6 weeks after embryo transfer,
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,
Delivery rate
Time Frame: 2-4 weeks post expected delivery date.
defined as the number of deliveries with at least one live birth or stillbirth (%)
2-4 weeks post expected delivery date.
Live birth rate
Time Frame: 2-4 weeks post expected delivery date.
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.
Cycle cancellation rate (with reason)
Time Frame: from treatment start until 10 weeks of pregnancy
defined as number of subjects dropping form the study at any time.
from treatment start until 10 weeks of pregnancy
Adverse Events related to the mother
Time Frame: from Informed consent signature until 2-4 week after delivery.
frequency and severity of adverse events related to the mother.
from Informed consent signature until 2-4 week after delivery.
Local tolerability
Time Frame: from the 4th day of treatment administration until 10 weeks post embryo transfer.
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.
Early Miscarriage rate
Time Frame: from 5 weeks post embryo transfer until the 12th week of pregnancy.
defined as a spontaneous loss of an intra-uterine pregnancy
from 5 weeks post embryo transfer until the 12th week of pregnancy.
Late miscarriage rate
Time Frame: after the 12th week of pregnancy until delivery.
defined as a spontaneous loss of an intra-uterine pregnancy
after the 12th week of pregnancy until delivery.
Ectopic pregnancy rate
Time Frame: from 5 weeks post embryo transfer until the 12th week of pregnancy.
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.
Adverse events related to the newborn.
Time Frame: 2-4 weeks after expected delivery.
frequency and severity of adverse events related to the newborn.
2-4 weeks after expected delivery.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progesterone Pharmacokinetic (PK) characterization
Time Frame: 4 days after treatment start.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 12, 2022

Primary Completion (Estimated)

September 1, 2024

Study Completion (Estimated)

March 1, 2025

Study Registration Dates

First Submitted

August 31, 2020

First Submitted That Met QC Criteria

September 8, 2020

First Posted (Actual)

September 16, 2020

Study Record Updates

Last Update Posted (Estimated)

March 5, 2024

Last Update Submitted That Met QC Criteria

March 4, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Infertility

Clinical Trials on Progesterone-IBSA Injectable Solution

3
Subscribe