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Study was terminated as per sponsor's decision
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| Name | Class |
|---|---|
| Merck Serono Middle East FZ LLC | INDUSTRY |
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This is a phase IIIb, interventional, multicenter, multinational, randomised, open-label, comparative trial which primary objective is to generate data on the ovarian stimulation profile obtained when Luveris® is started either on Day 1 or Day 6 in women in advanced reproductive age (36-42) undergoing Assisted Reproductive Technique (ART).
The subjects who complete the screening assessments and fulfil all the eligibility criteria will start down-regulation treatment on day 21-22 of the cycle.
Down-regulation treatment must start within 2 months following the screening visit. The routine long luteal phase protocol for Gonadotrophin-releasing hormone (GnRH) agonist treatment will be followed.
Once down-regulation has been confirmed, a pregnancy test will be performed within 1 week prior to start of Recombinant human follicle stimulating hormone (r-hFSH) treatment to rule out any pre-existing pregnancy. If the result is negative, the subject will be randomly assigned to one of the two treatment arms of the trial:
Randomization across the two treatment arms will be kept balanced in a 1:1 ratio. Subjects will be provided with a subject diary (including r-hCG and Crinone® administration and safety information) to record daily dosing information for GONAL-f® and Luveris®.
Follicular development will be monitored according to the center's standard practice by US and/or Oestradiol (E2) levels, until the protocol r-hCG requirement is met (i.e., at least 1 follicle greater or equal to 18 mm and 2 follicles greater or equal to 16 millimeter [mm]). After this, a single injection of 250 microgram (mcg) of r-hCG (Ovidrel®/Ovitrelle®), will be administered in order to induce final oocyte maturation.
At a time of 34-38 hours after r-hCG administration, oocytes will be recovered vaginally under US monitoring. Oocytes will then be fertilized in vitro and embryos replaced 2-3 days after oocyte recovery. Ovum pick up (OPU), in vitro fertilization (IVF), Embryo Transfer (ET) and luteal support will be performed as per center's standard practice. In addition, Crinone® 8% (progesterone gel) will be administered once daily.
A post-treatment safety visit will be performed for all subjects who received r-hCG (pregnant and non-pregnant) on post r-hCG Day 15-20. For subjects who have withdrawn from treatment (i.e. after starting Luveris® or GONAL f® but before r-hCG is given) this visit will take place 20-30 days after their first Luveris® or GONAL-f® treatment injection (excluding pregnancy testing).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Gonal-f®+Luveris® | Experimental | GONAL f® 300 international units [IU] per day as subcutaneous injection using liquid pen from stimulation Day 1-5 followed by Luveris® 150 IU per day lyophilized powder for subcutaneous injection from stimulation Day 1 until required recombinant human chorionic gonadotropin (r-hCG) level is met. The dose will be adjusted from stimulation Day 6 (increased or decreased) based upon the subject's ovarian response and according to the center's standard practice. |
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| Gonal-f® Followed by Luveris® | Experimental | GONAL-f® 300 IU per day as subcutaneous injection using liquid pen from stimulation Day 1-5 followed by Luveris® 150 IU per day lyophilized powder for subcutaneous injection from stimulation Day 6 until required r-hCG level is met. The dose will be adjusted from stimulation Day 6 (increased or decreased) based upon the subject's ovarian response and according to the center's standard practice. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GONAL-f® | Drug | GONAL f® 300 international units [IU] per day as subcutaneous injection using liquid pen. |
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| Measure | Description | Time Frame |
|---|---|---|
| Total Number of Oocytes Retrieved Per Subject Following Ovarian Stimulation | Ovarian stimulation was performed using in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). The total number of oocytes collected per subject following stimulation was reported. | 34-38 hours post r-hCG administration |
| Measure | Description | Time Frame |
|---|---|---|
| Total Dose and Mean Daily Dose of Follicle Stimulating Hormone (FSH) | Mean daily dose of FSH was to be determined by dividing the total daily dose by the number of stimulation days. | Screening |
| Total Number of Stimulation Treatment Days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Serono Middle East FZ LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Merck Serono Research Site | Dubai | United Arab Emirates |
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| ID | Title | Description |
|---|---|---|
| FG000 | Gonal-f®+Luveris | GONAL f® (Liquid Pen; 300 international units [IU] of per day) stimulation Day 1-5 then followed by Luveris® (vial/powder, 150 IU per day) from stimulation Day 1 until required r-hCG level was met. The dose was adjusted from stimulation Day 6 (increased or decreased) based upon the subject's ovarian response and according to the centre's standard practice. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Luveris® | Drug | Luveris® 150 IU per day lyophilized powder for subcutaneous injection. |
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| Recombinant human chorionic gonadotropin (r-hCG) | Biological | A single injection of r-hCG (Ovidrel®/Ovitrelle®) 250 mcg to induce final oocyte maturation. |
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The total number of stimulation treatment days for each subject was determined based on the treatment administration information collected in the case report form.
| 6 days post stimulation (Number of stimulation days+6 days) |
| Implantation Rate | The implantation rate was determined as number of fetal sacs divided by the number of embryos transferred post r-hCG administration. | 35-42 days post r-hCG administration |
| Number of Fetal Sacs With Activity | Number of fetal sacs with activity was evaluated by ultrasound scan (US) on Days 35-42 post r-hCG to confirm clinical pregnancy. | 35-42 days post r-hCG administration |
| Number of Fetal Sacs With Detectable Heart Beats | Number of fetal sacs with detectable heart beats was evaluated by US on Days 35-42 post r-hCG to confirm clinical pregnancy | 35-42 days post r-hCG administration |
| Total Pregnancy Rate and Clinical Pregnancy Rate | The subject was considered to have a positive pregnancy result if beta-hCG >10 international units per liter (IU/L) and the subject had not menstruated between post-r-hCG Days 15-20. Clinical pregnancy was defined as the existence of at least an US confirmed gestational sac in the uterus with fetal heart activity post-r-hCG Days 35-42. | 35-42 days post r-hCG administration |
| Cycle Cancellation Rate Prior to r-hCG | If the subject was not administered with r-hCG and withdrew prematurely from the trial, it was considered as cycle cancellation. | Up to 85 days |
| Number of Subjects With Biochemical Pregnancies | Biochemical pregnancy was defined as the pregnancy diagnosed only by the detection of hCG in serum or urine and that does not develop into a clinical pregnancy. Subjects with beta-hCG concentration greater than 10 IU/L were considered as biochemical pregnant. | 35 to 42 days post r-hCG administration |
| Number of Subjects With Multiple Pregnancies | Multiple pregnancy was defined as the existence of more than one ultrasound confirmed gestational sac in the uterus with fetal heart activity at post-r-hCG Days 35-42. | 35 to 42 days post r-hCG administration |
| Number of Subjects With Any Adverse Events (AEs), Serious AEs, AEs Leading to Death, and AEs Leading to Discontinuation | An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A serious AE is an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. | Baseline up to 15-20 days post r-hCG administration |
| FG001 | Gonal-f® Followed by Luveris | GONAL-f® (Liquid Pen; 300 IU per day) stimulation Day 1-5 then added Luveris® (vial/powder, 150 IU per day) from stimulation day 6 until required r-hCG level was met. The dose was adjusted from stimulation Day 6 (increased or decreased) based upon the subject's ovarian response and according to the centre's standard practice. |
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| NOT COMPLETED |
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Baseline analysis population included all the subjects randomized in the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Gonal-f®+Luveris | GONAL f® 300 international units [IU] per day as subcutaneous injection using liquid pen from stimulation Day 1-5 followed by Luveris® 150 IU per day lyophilized powder for subcutaneous injection from stimulation Day 1 until required recombinant human chorionic gonadotropin (r-hCG) level was met. The dose was adjusted from stimulation Day 6 (increased or decreased) based upon the subject's ovarian response and according to the center's standard practice. |
| BG001 | Gonal-f® Followed by Luveris | GONAL-f® 300 IU per day as subcutaneous injection using liquid pen from stimulation Day 1-5 followed by Luveris® 150 IU per day lyophilized powder for subcutaneous injection from stimulation Day 6 until required r-hCG level was met. The dose was adjusted from stimulation Day 6 (increased or decreased) based upon the subject's ovarian response and according to the center's standard practice. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Total Number of Oocytes Retrieved Per Subject Following Ovarian Stimulation | Ovarian stimulation was performed using in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). The total number of oocytes collected per subject following stimulation was reported. | Modified intention-to-treat (MITT) included all the subjects randomized into the trial who received at least 1 dose of Gonal-f® or Luveris®, and who completed the primary efficacy assessment (total number of oocytes retrieved per subject following recombinant human follicle stimulating hormone (r-hFSH) stimulation and r-hCG injection). | Posted | Mean | Standard Deviation | oocytes | 34-38 hours post r-hCG administration |
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| Secondary | Total Dose and Mean Daily Dose of Follicle Stimulating Hormone (FSH) | Mean daily dose of FSH was to be determined by dividing the total daily dose by the number of stimulation days. | Data was not analysed as per planned analysis due to frequent protocol violations/deviations, there was no subject eligible to be analyzed per protocol. | Posted | Screening |
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| Secondary | Total Number of Stimulation Treatment Days | The total number of stimulation treatment days for each subject was determined based on the treatment administration information collected in the case report form. | MITT included all the subjects randomized into the trial who received at least 1 dose of Gonal-f® or Luveris®, and who completed the primary efficacy assessment (total number of oocytes retrieved per subject following r-hFSH stimulation and r-hCG injection). | Posted | Mean | Standard Deviation | days | 6 days post stimulation (Number of stimulation days+6 days) |
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| Secondary | Implantation Rate | The implantation rate was determined as number of fetal sacs divided by the number of embryos transferred post r-hCG administration. | MITT included all subjects randomized in the trial who received at least 1 dose of Gonal-f® or Luveris®, and who completed primary efficacy assessment(total number of oocytes retrieved/subject following r-hFSH stimulation and r-hCG injection). 'N' signifies all subjects who showed positive pregnancy test and evaluable for this outcome measure. | Posted | Mean | Standard Deviation | fetal sacs/embryo transferred | 35-42 days post r-hCG administration |
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| Secondary | Number of Fetal Sacs With Activity | Number of fetal sacs with activity was evaluated by ultrasound scan (US) on Days 35-42 post r-hCG to confirm clinical pregnancy. | MITT included all subjects randomized in the trial who received at least 1 dose of Gonal-f® or Luveris®, and who completed primary efficacy assessment(total number of oocytes retrieved/subject following r-hFSH stimulation and r-hCG injection). 'N' signifies all participants who showed positive pregnancy test and evaluable for this outcome measure. | Posted | Mean | Standard Deviation | Fetal sacs | 35-42 days post r-hCG administration |
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| Secondary | Number of Fetal Sacs With Detectable Heart Beats | Number of fetal sacs with detectable heart beats was evaluated by US on Days 35-42 post r-hCG to confirm clinical pregnancy | MITT included all subjects randomized in the trial who received at least 1 dose of Gonal-f® or Luveris®, and who completed primary efficacy assessment(total number of oocytes retrieved/subject following r-hFSH stimulation and r-hCG injection). 'N' signifies all participants who showed positive pregnancy test and evaluable for this outcome measure. | Posted | Mean | Standard Deviation | Fetal sacs | 35-42 days post r-hCG administration |
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| Secondary | Total Pregnancy Rate and Clinical Pregnancy Rate | The subject was considered to have a positive pregnancy result if beta-hCG >10 international units per liter (IU/L) and the subject had not menstruated between post-r-hCG Days 15-20. Clinical pregnancy was defined as the existence of at least an US confirmed gestational sac in the uterus with fetal heart activity post-r-hCG Days 35-42. | MITT included all the subjects randomized into the trial who received at least 1 dose of Gonal-f® or Luveris®, and who completed the primary efficacy assessment (total number of oocytes retrieved per subject following r-hFSH stimulation and r-hCG injection). | Posted | Number | percentage of subjects | 35-42 days post r-hCG administration |
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| Secondary | Cycle Cancellation Rate Prior to r-hCG | If the subject was not administered with r-hCG and withdrew prematurely from the trial, it was considered as cycle cancellation. | MITT included all the subjects randomized into the trial who received at least 1 dose of Gonal-f® or Luveris®, and who completed the primary efficacy assessment (total number of oocytes retrieved per subject following r-hFSH stimulation and r-hCG injection). | Posted | Number | percentage of subjects | Up to 85 days |
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| Secondary | Number of Subjects With Biochemical Pregnancies | Biochemical pregnancy was defined as the pregnancy diagnosed only by the detection of hCG in serum or urine and that does not develop into a clinical pregnancy. Subjects with beta-hCG concentration greater than 10 IU/L were considered as biochemical pregnant. | MITT included all the subjects randomized into the trial who received at least 1 dose of Gonal-f® or Luveris®, and who completed the primary efficacy assessment (total number of oocytes retrieved per subject following r-hFSH stimulation and r-hCG injection). | Posted | Number | subjects | 35 to 42 days post r-hCG administration |
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| Secondary | Number of Subjects With Multiple Pregnancies | Multiple pregnancy was defined as the existence of more than one ultrasound confirmed gestational sac in the uterus with fetal heart activity at post-r-hCG Days 35-42. | MITT included all subjects randomized into trial who received at least 1 dose of Gonal-f® or Luveris®, and completed the primary efficacy assessment (total number of oocytes retrieved per subject following r-hFSH stimulation and r-hCG injection). 'N'=signifies all subjects who showed positive pregnancy test and evaluable for this outcome measure. | Posted | Number | subjects | 35 to 42 days post r-hCG administration |
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| Secondary | Number of Subjects With Any Adverse Events (AEs), Serious AEs, AEs Leading to Death, and AEs Leading to Discontinuation | An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A serious AE is an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. | Safety population included all randomized subjects who received at least one dose of the trial treatment. | Posted | Number | subjects | Baseline up to 15-20 days post r-hCG administration |
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Baseline up to 15-20 days post r-hCG administration
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Gonal-f®+Luveris | GONAL f® 300 international units [IU] per day as subcutaneous injection using liquid pen from stimulation Day 1-5 followed by Luveris® 150 IU per day lyophilized powder for subcutaneous injection from stimulation Day 1 until required recombinant human chorionic gonadotropin (r-hCG) level was met. The dose was adjusted from stimulation Day 6 (increased or decreased) based upon the subject's ovarian response and according to the center's standard practice. | 4 | 89 | 24 | 89 | ||
| EG001 | Gonal-f® Followed by Luveris | GONAL-f® 300 IU per day as subcutaneous injection using liquid pen from stimulation Day 1-5 followed by Luveris® 150 IU per day lyophilized powder for subcutaneous injection from stimulation Day 6 until required r-hCG level was met. The dose was adjusted from stimulation Day 6 (increased or decreased) based upon the subject's ovarian response and according to the center's standard practice. | 5 | 85 | 27 | 85 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA Version 15.1 | Non-systematic Assessment |
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| Ovarian cyst | Reproductive system and breast disorders | MedDRA Version 15.1 | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Overdose | Injury, poisoning and procedural complications | MedDRA Version 15.1 | Non-systematic Assessment |
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| Oestradiol increased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
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| Progesterone increased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
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| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA Version 15.1 | Non-systematic Assessment |
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| Breast pain | Reproductive system and breast disorders | MedDRA Version 15.1 | Non-systematic Assessment |
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Study was terminated as per sponsor's decision.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Merck KGaA Communication Center | Merck Serono, a division of Merck KGaA | +49-6151-72-5200 | service@merckgroup.com |
| ID | Term |
|---|---|
| D007246 | Infertility |
| ID | Term |
|---|---|
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| C571801 | follitropin alfa |
| D037101 | Luteinizing Hormone, beta Subunit |
| D006063 | Chorionic Gonadotropin |
| ID | Term |
|---|---|
| D007986 | Luteinizing Hormone |
| D006065 | Gonadotropins, Pituitary |
| D006062 | Gonadotropins |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010908 | Pituitary Hormones, Anterior |
| D010907 | Pituitary Hormones |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D010926 | Placental Hormones |
| D011257 | Pregnancy Proteins |
| D011506 | Proteins |
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