A Trial to Compare the Ovarian Response of REKOVELLE and GONAL-F in Conventional Dosing in Women Undergoing Controlled Ovarian Stimulation (ADAPT-1)

A Randomised, Controlled, Assessor-blind, Parallel Groups, Multicentre, Multinational Trial Comparing the Ovarian Response of a Starting Dose of 15 μg Follitropin Delta (REKOVELLE) to a Starting Dose of 225 IU Follitropin Alfa (GONAL-F) in Conventional Regimens in Controlled Ovarian Stimulation in Women Undergoing an Assisted Reproductive Technology Programme

Hormone preparations like REKOVELLE and GONAL-F are used to make the body produce multiple egg sacs, allowing more eggs to be collected from women undergoing infertility treatment.

The main purpose of this trial is to see how many eggs are produced with a starting dose of 15 µg REKOVELLE compared to a starting dose of 225 IU GONAL-F. This research is intended to provide more knowledge about REKOVELLE, including the doses given in the trial.

Study Overview

• Status: Recruiting
• Conditions: Infertility
• Intervention / Treatment: Drug: REKOVELLE (Follitropin Delta); Other: GONAL-F (Follitropin Alfa)

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Global Clinical Compliance; Phone Number: +1 833-548-1402 (US/Canada); Email: DK0-Disclosure@ferring.com
• Study Contact Backup: Name: Global Clinical Compliance; Phone Number: +1 862-286-5200 (outside US); Email: DK0-Disclosure@ferring.com

Study Locations

• Austria
  • Wals-Siezenheim, Austria
    • Recruiting
    • Ferring Investigational Site
  • Wien, Austria
    • Recruiting
    • Ferring Investigational Site
• France
  • Montpellier, France
    • Recruiting
    • Ferring Investigational Site
  • Paris, France
    • Recruiting
    • Ferring Investigational Site
• Italy
  • Firenze, Italy
    • Recruiting
    • Ferring Investigational Site
  • Milano, Italy
    • Recruiting
    • Ferring Investigational Site
  • Napoli, Italy
    • Recruiting
    • Ferring Investigational Site
  • Roma, Italy
    • Recruiting
    • Ferring Investigational Site
• Spain
  • Alicante, Spain
    • Recruiting
    • Ferring Investigational Site
  • Barcelona, Spain
    • Recruiting
    • Ferring Investigational Site
  • Bilbao, Spain
    • Recruiting
    • Ferring Investigational Site
  • Madrid, Spain
    • Recruiting
    • Ferring Investigational Site
  • Madrid, Spain
    • Active, not recruiting
    • Ferring Investigational Site
  • Malaga, Spain
    • Recruiting
    • Ferring Investigational Site
  • Valladolid, Spain
    • Recruiting
    • Ferring Investigational Site
• United Kingdom
  • Coventry, United Kingdom
    • Recruiting
    • Ferring Investigational Site
  • Liverpool, United Kingdom
    • Recruiting
    • Ferring Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Infertile women aged 18-40 years
• Diagnosed with tubal infertility, unexplained infertility, mild endometriosis (stage I/II) or partners with decreased sperm quality
• Medically prepared for in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI)
• Infertility for at least one year for participants below 37 years or for at least 6 months for participants above 38 years
• Regular menstrual cycles of 21-35 days.

Exclusion Criteria:

• Known condition of not functioning ovaries
• Known advanced endometriosis (stage III/IV)
• Considered unsuitable for controlled ovarian stimulation with a dosing regimen corresponding to approximately 225 IU/day gonadotropin, as judged by the investigator
• History of previous episode of OHSS or exuberant ovarian response to gonadotropins, and polycystic ovarian syndrome
• Any known hormonal or metabolic abnormalities which can compromise participation in the trial
• Known tumors of the ovary, breast, uterus, adrenal gland, pituitary or hypothalamus

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: REKOVELLE (Follitropin Delta)	Drug: REKOVELLE (Follitropin Delta); REKOVELLE administered as single daily subcutaneous injections in the abdomen. The starting dose of REKOVELLE is 15 μg fixed for the first four stimulation days. Dose adjustments may be implemented on the day of starting the gonadotropin-releasing hormone (GnRH) antagonist (stimulation day 5 or day 6) or later, can occur no more frequently than every second day. At each dose adjustment, the daily REKOVELLE dose can be increased or decreased by 5 μg based on the subject's response. The minimum REKOVELLE dose is 5 μg and the maximum REKOVELLE is 20 μg. Subjects can be treated for a maximum of 20 days.
Active Comparator: GONAL-F (Follitropin Alfa)	Other: GONAL-F (Follitropin Alfa); GONAL-F administered as single daily subcutaneous injections in the abdomen. The starting dose of GONAL-F is 225 IU fixed for the first four stimulation days. Dose adjustments may be implemented on the day of starting the GnRH antagonist (stimulation day 5 or day 6) or later, can occur no more frequently than every second day. At each dose adjustment, the daily GONAL-F dose may be adjusted by 75 IU based on the subject's response. The minimum GONAL-F dose is 75 IU and the maximum GONAL-F dose is 300 IU. Subjects can be treated for a maximum of 20 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of oocytes retrieved	The number of oocytes retrieved will be recorded at the oocyte retrieval visit.	On day of oocyte retrieval (Up to 22 days after start of stimulation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of follicles (total) at end-of-stimulation	Counted by ultrasound for the right and left ovary for each subject.	At end-of-stimulation (up to 20 stimulation days)
Size of the follicles at end-of-stimulation	Counted by ultrasound for the right and left ovary for each subject.	At end-of-stimulation (up to 20 stimulation days)
Serum concentrations of estradiol at end-of-stimulation	Blood samples for analysis of circulating concentrations of estradiol will be drawn.	At end-of-stimulation (up to 20 stimulation days)
Serum concentrations of progesterone at end-of-stimulation	Blood samples for analysis of circulating concentrations of progesterone will be drawn.	At end-of-stimulation (up to 20 stimulation days)
Number of fertilized oocytes	The number of pronuclei will be counted after insemination. Fertilized oocytes with 2 pronuclei (2PN) will be regarded as correctly fertilized.	On day 1 after oocyte retrieval (up to 23 days after start of stimulation)
Fertilization rate	The fertilization rate was defined as the number of oocytes with 2PN divided by the number of oocytes retrieved.	On day 1 after oocyte retrieval (up to 23 days after start of stimulation)
Number of Blastocysts and Number of Good Quality Blastocysts	Number of blastocysts and number of good quality blastocysts on Day 5 or 6 will be presented. The quality evaluation of blastocysts consisted of assessment of three parameters, as per the Gardner & Schoolcraft system: blastocyst expansion and hatching status (graded: 1-6), inner cell mass (graded: A-D) and trophectoderm (graded: A-D). A good-quality blastocyst was defined as a blastocyst of grade 3BB or higher.	On Day 5 or Day 6 (as applicable) after oocyte retrieval (up to 27 or 28 days after start of stimulation)
Total gonadotropin dose	Calculated by start dates, end dates and daily dose of investigational medicinal product (IMP).	Up to 20 stimulation days
Number of stimulation days	Calculated by start dates and end dates.	Up to 20 stimulation days
Proportion of subjects with early ovarian hyperstimulation syndrome (OHSS) (overall and by grade) and/or preventive interventions for early OHSS	Early OHSS is defined as OHSS with onset ≤9 days after triggering of final follicular maturation. Classification of grade was according to Golan's classification system, and all OHSS cases were graded as mild, moderate or severe.	Up to 9 days after triggering of final follicular maturation

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals
• Investigators: Study Director: Global Clinical Compliance, Ferring Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2022
• Primary Completion (Estimated): April 15, 2024
• Study Completion (Estimated): April 15, 2024

Study Registration Dates

• First Submitted: November 16, 2021
• First Submitted That Met QC Criteria: February 21, 2022
• First Posted (Actual): March 2, 2022

Study Record Updates

• Last Update Posted (Estimated): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Follicle Stimulating Hormone
• Other Study ID Numbers: 000401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No