Clinical trial NCT04163458: Comparison of MENOPUR Liquid and Powder in Women Undergoing Assisted Reproductive Technology (ART)
Official title: A Randomized, Double-blind Double-dummy Trial Comparing MENOPUR Solution for Injection in a Pre-filled Pen and MENOPUR Powder and Solvent for Solution for Injection (Menotropins for Injection) in a GnRH Agonist Cycle in Women Aged 18-42 Years Undergoing an Assisted Reproductive Technology Program
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infertility
Keywords: Controlled Ovarian Stimulation
Assisted Reproductive Technology
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-11-14
Enrollment: 405
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Development of multiple follicles and pregnancy in ovulatory women undergoing controlled ovarian stimulation as part of an assisted reproductive technology (ART) cycle.


Eligibility criteria: Inclusion Criteria:

* Signed informed consents, prior to any trial-related procedure.
* Females between the ages of 18 and 42 years. The participants must be at least 18 years (including the 18th birthday) when they sign the informed consent and no more than 42 years (up to the day before the 43rd birthday) at the time of randomization who desire pregnancy.
* Body mass index (BMI) between 17.5 and 38.0 kg/m\^2 (both inclusive) at screening.
* Regular menstrual cycles of 24 to 35 days, presumed to be ovulatory.
* Documented history of infertility for at least 12 months before randomization for women ≤35 years or for at least 6 months for women ≥36 years. Women with documented bilateral tubal occlusion or male factor infertility requiring the use of donor sperm established as a cause of infertility are eligible at diagnosis.
* Early follicular phase (cycle day 2-4) serum FSH level between 1 and 12 IU/L (results obtained within 3 months prior to randomization).
* Male partner with semen analysis that is at least adequate for intracytoplasmic sperm injection (ICSI) at screening or within 6 months prior to the screening date. Partners with severe male factors requiring invasive or surgical sperm retrieval may not be used. Use of donor sperm is allowed.
* At least 1 cycle with no fertility medication immediately prior to screening.
* Hysterosalpingography, hysteroscopy, or saline hysterosonogram documenting uterine anatomy appropriate for ART at screening or within 12 months prior to screening.
* Transvaginal ultrasound documenting presence and adequate visualization of both ovaries, without evidence of clinically significant abnormality (e.g., endometrioma ≥3 cm, no dermoid cysts) and normal adnexa (e.g., no hydrosalpinx) at screening. Both ovaries must be accessible for oocyte retrieval.

Exclusion Criteria:

* More than two previous controlled ovarian stimulation cycles for in vitro fertilization (IVF)/ICSI
* Known stage III-IV endometriosis (American Society for Reproductive Medicine, 2012).
* Oocyte donor or embryo recipient; gestational or surrogate carrier.
* Known history of recurrent miscarriage (defined as three consecutive losses after ultrasound confirmation of pregnancy \[excluding ectopic pregnancy\] and before week 24 of pregnancy).
* Participant's male partner, with obvious leukospermia (\>2 million white blood cells/mL) or signs of infection in semen sample within 6 months of the participant's screening. If either of these conditions exists, the male should be treated with antibiotics and retested prior to the participant's randomization.
* Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of these events.
* Any known endocrine (total testosterone, prolactin and TSH) or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney) with the exception of controlled thyroid function disease.
* Known tumors of the ovary, breast, uterus, adrenal gland, pituitary or hypothalamus which would contraindicate the use of gonadotrophins.
* Any abnormal finding of clinical chemistry, hematology and vital signs at screening, which is judged clinically significant by the investigator.
* Pregnancy (negative urine pregnancy test must be documented at screening and prior to the first investigational medicinal product \[IMP\] administration), or contraindication to pregnancy.
* Hypersensitivity to any active ingredient or excipients in the medicinal products used in this trial.

Primary outcomes:
measure: Number of Fertilized (2 Pronuclei [2PN]) Oocytes
timeFrame: On Day 1 after oocyte retrieval (up to 23 days after start of stimulation)
Secondary outcomes:
measure: Positive Beta Human Chorionic Gonadotropin (βhCG) Rate
timeFrame: 10-14 days after blastocyst transfer (up to approximately 6 weeks after start of stimulation)
measure: Clinical Pregnancy Rate
timeFrame: 5-6 weeks after blastocyst transfer (up to approximately 10 weeks after start of stimulation)
measure: Ongoing Pregnancy Rate
timeFrame: 8-9 weeks after blastocyst transfer (up to approximately 13 weeks after start of stimulation)
measure: Early Pregnancy Loss
timeFrame: 8-9 weeks after blastocyst transfer (up to approximately 13 weeks after start of stimulation)
measure: Follicular Development on Stimulation Day 6
timeFrame: At stimulation Day 6
measure: Follicular Development on Last Day of Stimulation
timeFrame: At last day of stimulation (up to 20 stimulation days)
measure: Serum Follicle-stimulating Hormone (FSH) Concentration
timeFrame: At Day 6, last day of stimulation (up to 20 stimulation days) and at oocyte retrieval (up to 22 days after start of stimulation)
measure: Serum Anti-Müllerian Hormone (AMH) Concentration
timeFrame: At the last day of stimulation (up to 20 stimulation days) and at end-of-trial (up to approximately 6 months from the start of screening)
measure: Human Chorionic Gonadotropin (hCG) Concentration
timeFrame: At Day 6 and last day of stimulation (up to 20 stimulation days)
measure: Luteinizing Hormone (LH) Concentration
timeFrame: At Day 6 and last day of stimulation (up to 20 stimulation days)
measure: Progesterone (P4) Concentration
timeFrame: At Day 6 and last day of stimulation (up to 20 stimulation days)
measure: Estradiol (E2) Concentration
timeFrame: At stimulation Day 6 and last day of stimulation (up to 20 stimulation days)
measure: Number of Oocytes Retrieved
timeFrame: On day of oocyte retrieval (up to 22 days after start of stimulation)
measure: Number of Metaphase II (MII) Oocytes
timeFrame: On day of oocyte retrieval (up to 22 days after start of stimulation)
measure: Fertilization Rate
timeFrame: On Day 1 after oocyte retrieval (up to 23 days after start of stimulation)
measure: Number of Blastocysts and Number of Good-Quality Blastocysts 5 Days After Oocyte Retrieval
timeFrame: On Day 5 after oocyte retrieval (up to 27 days after start of stimulation)
measure: Total Gonadotropin Dose
timeFrame: Up to 20 stimulation days
measure: Number of Stimulation Days
timeFrame: Up to 20 stimulation days
measure: Proportion of Participants With Ovarian Hyperstimulation Syndrome (OHSS)
timeFrame: ≤9 days after triggering of final follicular maturation (early OHSS), >9 days after triggering of final follicular maturation until 21-28 days after last IMP dose or up to ongoing pregnancy 8-9 weeks after transfer in pregnant participants (late OHSS)
measure: Frequency of Adverse Events (AEs)
timeFrame: From the time of signed informed consent for participation in the trial until the end-of-trial visit (up to approximately 6 months)
measure: Intensity of AEs
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Alanine Aminotransferase
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Aspartate Aminotransferase
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Blood Urea Nitrogen
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Calcium
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Chloride
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Creatinine
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Gamma Glutamyl Transferase
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Glucose
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Potassium
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Sodium
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Egfr African American
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Egfr Non-afr. American
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Erythrocytes
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Leukocytes
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Hemoglobin
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Hematocrit
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Platelets
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Basophils
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Basophils/Leukocytes
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Eosinophils
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Eosinophils/Leukocytes
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Lymphocytes
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Lymphocytes/Leukocytes
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Monocytes
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Monocytes/Leukocytes
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Neutrophils
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Neutrophils/Leukocytes
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters
timeFrame: From the start of screening until the end-of-trial (up to approximately 6 months)
measure: Frequency of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Participant During the Stimulation Period
timeFrame: Up to 20 stimulation days
measure: Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Participant During the Stimulation Period
timeFrame: Up to 20 stimulation days
measure: Proportion of Participants With Treatment-induced Anti-MENOPUR Antibodies. Overall as Well as With Neutralizing Capacity
timeFrame: Up to 28 days after end of the stimulation period (simulation period up to 20 days)
measure: Number of Participants With Potential Technical Malfunctions of the Administration Pen
timeFrame: Up to 20 stimulation days
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Fertility Treatment Center
state: Arizona
city: San Diego
country: United States
facility: Fertility Specialists Medical Group - San Diego Center for Reproductive Surgery
state: California
city: Farmington
country: United States
facility: Center for Advanced Reproductive Services PC
state: Connecticut
city: New Haven
country: United States
facility: Yale Fertility Center
state: Connecticut
city: Miami
country: United States
facility: Fertility and IVF Center of Miami
state: Florida
city: Winter Park
country: United States
facility: Center for Reproductive Medicine
state: Florida
city: Boise
country: United States
facility: Idaho Center for Reproductive Medicine
state: Idaho
city: Chicago
country: United States
facility: Fertility Centers of Illinois
state: Illinois
city: Hoffman Estates
country: United States
facility: InVia Fertility Specialists, SC
state: Illinois
city: Baton Rouge
country: United States
facility: Fertility Answers, LLC
state: Louisiana
city: Las Vegas
country: United States
facility: SIRM Fertility Center
state: Nevada
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: Oklahoma City
country: United States
facility: OU Physicians Reproductive Medicine
state: Oklahoma
city: Abington
country: United States
facility: Abington Reproductive Medicine
state: Pennsylvania
city: Memphis
country: United States
facility: Fertility Associates of Memphis, PLLC
state: Tennessee
city: Bedford
country: United States
facility: Center for Assisted Reproduction
state: Texas
city: Houston
country: United States
facility: Houston Fertility Institute
state: Texas
city: Webster
country: United States
facility: Center of Reproductive Medicine
state: Texas
Study officials:
affiliation: Ferring Pharmaceuticals
name: Global Clinical Compliance
role: STUDY_DIRECTOR
References: