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Completed

NCT Number: NCT04163458

Comparison of MENOPUR Liquid and Powder in Women Undergoing Assisted Reproductive Technology (ART)

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

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Key information

Conditions

Infertility Genital Diseases Urogenital Diseases

Age range

18 year–42 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 3

Primary location

Fertility Treatment Center, Tempe, Arizona, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

MENOPUR solution for injection in pre-filled pen, 1200 IU/1.92 mL

Drug

Solution for injection in pre-filled pen, subcutaneous administration

Other names: Highly purified menotropin

MENOPUR powder and solvent for solution for injection, 75 IU

Drug

Solution for injection in vials (powder and diluent), subcutaneous administration

Other names: Highly purified menotropin

Placebo (for MENOPUR solution for injection in pre-filled pen)

Other

Solution for injection in pre-filled pen, subcutaneous administration

Placebo (for MENOPUR powder and solvent for solution for injection)

Other

Solution for injection in vials (powder and diluent); subcutaneous administration

Primary outcomes

  1. Number of Fertilized (2 Pronuclei [2PN]) Oocytes

    Time frame: On Day 1 after oocyte retrieval (up to 23 days after start of stimulation)

    Fertilized oocytes with 2PN were regarded as correctly fertilized.

Secondary outcomes

  1. Positive Beta Human Chorionic Gonadotropin (βhCG) Rate

    Time frame: 10-14 days after blastocyst transfer (up to approximately 6 weeks after start of stimulation)

    A blood serum βhCG test was obtained 10-14 days after blastocyst transfer. If the test was positive according to the local laboratory's reference ranges, this confirmed a positive βhCG.

  2. Clinical Pregnancy Rate

    Time frame: 5-6 weeks after blastocyst transfer (up to approximately 10 weeks after start of stimulation)

    Clinical pregnancy was based on detection of at least 1 intrauterine gestational sac with fetal heart beat on transvaginal ultrasound.

  3. Ongoing Pregnancy Rate

    Time frame: 8-9 weeks after blastocyst transfer (up to approximately 13 weeks after start of stimulation)

    Ongoing pregnancy was based on detection of at least 1 intrauterine viable fetus by transvaginal or abdominal ultrasound

  4. Early Pregnancy Loss

    Time frame: 8-9 weeks after blastocyst transfer (up to approximately 13 weeks after start of stimulation)

    Number of participants with early pregnancy loss defined as a positive βhCG tests but no ongoing pregnancy.

  5. Follicular Development on Stimulation Day 6

    Time frame: At stimulation Day 6

    The total number of follicles and the number of follicles per size category were reported.

  6. Follicular Development on Last Day of Stimulation

    Time frame: At last day of stimulation (up to 20 stimulation days)

    The total number of follicles and the number of follicles per size category were reported.

  7. Serum Follicle-stimulating Hormone (FSH) Concentration

    Time frame: At Day 6, last day of stimulation (up to 20 stimulation days) and at oocyte retrieval (up to 22 days after start of stimulation)

    The concentration of serum FSH was measured. The median and IQR of FSH levels on stimulation day 6, End of stimulation and Oocyte Retrieval visit are presented.

  8. Serum Anti-Müllerian Hormone (AMH) Concentration

    Time frame: 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)

    The concentration of serum AMH was measured. The median and IQR of AMH levels on End of stimulation and End of Trial are presented.

  9. Human Chorionic Gonadotropin (hCG) Concentration

    Time frame: At Day 6 and last day of stimulation (up to 20 stimulation days)

    The concentration of hCG was measured. The median and IQR of hCG levels on stimulation day 6 and End of stimulation are presented.

  10. Luteinizing Hormone (LH) Concentration

    Time frame: At Day 6 and last day of stimulation (up to 20 stimulation days)

    The concentration of LH was measured. The median and IQR of LH levels on stimulation day 6 and End of stimulation are presented.

  11. Progesterone (P4) Concentration

    Time frame: At Day 6 and last day of stimulation (up to 20 stimulation days)

    The concentration of P4 was measured. The median and IQR of P4 levels on stimulation day 6 and End of stimulation are presented.

  12. Estradiol (E2) Concentration

    Time frame: At stimulation Day 6 and last day of stimulation (up to 20 stimulation days)

    The concentration of E2 was measured. The median and IQR of E2 levels on stimulation day 6 and End of stimulation are presented.

  13. Number of Oocytes Retrieved

    Time frame: On day of oocyte retrieval (up to 22 days after start of stimulation)

    The number of oocytes retrieved was recorded at the oocyte retrieval visit.

  14. Number of Metaphase II (MII) Oocytes

    Time frame: On day of oocyte retrieval (up to 22 days after start of stimulation)

    Maturity stage was assessed prior to undergoing ICSI. Maturity stage was categorized as germinal vesicle, metaphase I, metaphase II, degenerated or other.

  15. Fertilization Rate

    Time frame: On Day 1 after oocyte retrieval (up to 23 days after start of stimulation)

    Fertilization rate(%) is the number of 2PN oocytes divided by the number of oocytes retrieved.

  16. Number of Blastocysts and Number of Good-Quality Blastocysts 5 Days After Oocyte Retrieval

    Time frame: On Day 5 after oocyte retrieval (up to 27 days after start of stimulation)

    The number of blastocysts (total and good-quality) was reported. Blastocyst quality was assessed by blastocyst expansion and hatching status, blastocyst inner cell mass grading, and trophectoderm grading. The scoring was based on the classification system by Gardner and Schoolcraft, with additional categories for inner cell mass (degenerative or no inner cell mass) and trophectoderm (degenerative or very large cells)

  17. Total Gonadotropin Dose

    Time frame: Up to 20 stimulation days

    The gonadotropin starting dose was 225 IU for the first 5 days, followed by individual adjustments according to the participant's follicular response. Dose adjustment should be 75 IU per adjustment. Gonadotropin was to be initiated within 3 days of confirmed downregulation.

  18. Number of Stimulation Days

    Time frame: Up to 20 stimulation days

    Calculated by start dates and end dates.

  19. Proportion of Participants With Ovarian Hyperstimulation Syndrome (OHSS)

    Time frame: ≤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)

    OHSS was defined as the total of early OHSS with onset ≤9 days after triggering of final follicular maturation, and late OHSS with onset >9 days after triggering of final follicular maturation.

  20. Frequency of Adverse Events (AEs)

    Time frame: From the time of signed informed consent for participation in the trial until the end-of-trial visit (up to approximately 6 months)

    Any AE occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or pre-existing medical condition that worsens in intensity after start of IMP and before the end-of-trial visit was considered treatment-emergent, and is presented for this endpoint.

  21. Intensity of AEs

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    The intensity of an AE was classified using the following 3-point scale: Mild = Awareness of signs or symptoms, but no disruption of usual activity. Moderate = Event sufficient to affect usual activity (disturbing). Severe = Inability to work or perform usual activities (unacceptable).

  22. Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Alanine Aminotransferase

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of clinical chemistry parameters.

  23. Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Aspartate Aminotransferase

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of clinical chemistry parameters.

  24. Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Blood Urea Nitrogen

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of clinical chemistry parameters.

  25. Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Calcium

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of clinical chemistry parameters.

  26. Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Chloride

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of clinical chemistry parameters.

  27. Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Creatinine

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of clinical chemistry parameters.

  28. Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Gamma Glutamyl Transferase

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of clinical chemistry parameters.

  29. Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Glucose

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of clinical chemistry parameters.

  30. Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Potassium

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of clinical chemistry parameters.

  31. Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Sodium

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of clinical chemistry parameters.

  32. Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Egfr African American

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of clinical chemistry parameters.

  33. Changes in Circulating Levels of Clinical Chemistry Parameters Compared to Baseline: Egfr Non-afr. American

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of clinical chemistry parameters.

  34. Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Erythrocytes

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of haematology parameters.

  35. Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Leukocytes

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of haematology parameters.

  36. Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Hemoglobin

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of haematology parameters.

  37. Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Hematocrit

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of haematology parameters.

  38. Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Platelets

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of haematology parameters.

  39. Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Basophils

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of haematology parameters.

  40. Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Basophils/Leukocytes

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of haematology parameters.

  41. Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Eosinophils

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of haematology parameters.

  42. Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Eosinophils/Leukocytes

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of haematology parameters.

  43. Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Lymphocytes

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of haematology parameters.

  44. Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Lymphocytes/Leukocytes

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of haematology parameters.

  45. Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Monocytes

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of haematology parameters.

  46. Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Monocytes/Leukocytes

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of haematology parameters.

  47. Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Neutrophils

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of haematology parameters.

  48. Changes in Circulating Levels of Haematology Parameters Compared to Baseline: Neutrophils/Leukocytes

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    Blood samples were collected for the analysis of haematology parameters.

  49. Proportion of Subjects With Markedly Abnormal Changes of Clinical Parameters and Haematology Parameters

    Time frame: From the start of screening until the end-of-trial (up to approximately 6 months)

    The table represents the percentage of participants in each group with normal baseline values and markedly abnormal end-of-stimulation or end-of-trial visit values.

    It is only parameters with markedly abnormal values at end of stimulation or end of trial visit which are represented. Parameters with normal baseline values and normal end of stimulation and end of trial values are not represented.

  50. Frequency of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Participant During the Stimulation Period

    Time frame: Up to 20 stimulation days

    Assessed by the participant during the stimulation period. Participants assessed the injection site reactions (redness, pain, itching, swelling and bruising) three times daily: immediately after the injection, 30 minutes after the injection and 24 hours after the injection.

    Total Number of events include all categories None, Mild, Moderate and Severe. Percentage of events with injection site reactions as a sum of the categories Mild, Moderate and Severe is presented.

  51. Intensity of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Participant During the Stimulation Period

    Time frame: Up to 20 stimulation days

    Assessed by the participant during the stimulation period as mild, moderate or severe.

    Participants assessed the injection site reactions (redness, pain, itching, swelling and bruising) three times daily: immediately after the injection, 30 minutes after the injection and 24 hours after the injection.

  52. Proportion of Participants With Treatment-induced Anti-MENOPUR Antibodies. Overall as Well as With Neutralizing Capacity

    Time frame: Up to 28 days after end of the stimulation period (simulation period up to 20 days)

    Measured by presence of anti-MENOPUR antibodies.

    95% Clopper-Pearson confidence interval has been reported in this endpoint.

  53. Number of Participants With Potential Technical Malfunctions of the Administration Pen

    Time frame: Up to 20 stimulation days

    Number of participants With Potential Technical malfunctions of the Administration Pen were recorded.

Sponsors and collaborators

Lead sponsor

Ferring Pharmaceuticals

Industry

Registry information

Official study 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

Acronym: CLARA

Important dates

Study start
2019
Primary completion
2021
Study completion
2021
First posted
Nov 14, 2019
Registry last updated
Nov 7, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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