Neonates, Pregnancy
Conditions
Keywords
Neonatal outcome, Congenital malformations, Ovulation Induction, Follow-up
Brief summary
The objective of follow-up study P05713 is to evaluate whether corifollitropin alfa (Org 36286) treatment for the induction of monofollicular growth in women who underwent ovulation induction (OI) in base study P05693 (NCT00697255) is safe for pregnant participants and their offspring.
Detailed description
Base study P05693 (NCT00697255) was planned to include two separate stages (Ia+Ib and II). Stage Ia was open-label and uncontrolled in a small cohort of women (n=5) to explore whether the intended dosing regimen of corifollitropin alfa followed by daily low dose recombinant Follicle Stimulating Hormone (recFSH) would provide an appropriate response in eligible participants meeting all inclusion and none of the exclusion criteria. Stage Ib was open-label and uncontrolled in a small cohort of women (n=3) to explore whether the intended dosing regimen of corifollitropin alfa followed by daily low dose Human Chorion Gonadotropin (hCG) would provide an appropriate response in eligible participants meeting all inclusion and none of the exclusion criteria. Stage II was planned to be open-label and randomized (n=40) to evaluate whether the intended dosing regimen of corifollitropin alfa followed by low dose recFSH (n=20) or hCG (n=20) would provide an appropriate response in eligible participants meeting all inclusion and none of the exclusion criteria. P05713 is a follow-up (FU) study to prospectively monitor pregnancy, delivery, and neonatal outcome of women who became ongoing pregnant during base study P05693 (NCT00697255). For this trial, no study specific assessments will be required and no treatment will be administered, but information as obtained in standard practice will be used. Enrollment will begin when the first ongoing pregnancy resulting from the base study has been established (ultrasound ≥ 10 weeks after bolus injection of hCG).
Interventions
DRUGcorifollitropin alfa
SC injection(s) of corifollitropin alfa (30 mcg) was administered the first, second or third day after onset of progestagen-induced withdrawal bleeding in base study P05693 (NCT00697255). No treatment was administered on the current follow-up study.
Daily injections of SC recFSH (50 IU/75 IU) were administered as soon as the largest follicle reached a size ≥ 12 mm 4 days after a corifollitropin alfa injection (on stimulation day 5, 9 or 13) in base study P05693 (NCT00697255). No treatment was administered on the current follow-up study.
BIOLOGICALhuman Chorion Gonadotropin (hCG)
Daily injections of SC hCG injection were administered as soon as the largest follicle reached a size ≥ 12 mm 4 days after a corifollitropin alfa injection (on stimulation day 5, 9 or 13) in base study P05693 (NCT00697255). No treatment was administered on the current follow-up study.
BIOLOGICALhCG Bolus injection
Bolus injection of SC hCG was administered in base study P05693 (NCT00697255) to induce final oocyte maturation if at least one follicle was ≥18 mm and no more than two follicles ≥15 mm were observed. No treatment was administered on the current follow-up study.
Sponsors
Organon and Co
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 39 Years
Healthy volunteers
No
Inclusion criteria
* Participants who participated in base study P05693 (NCT00697255) and received at least one dose of corifollitropin alfa * Ongoing pregnancy confirmed by ultrasound at least 10 weeks after bolus injection of hCG in base study P05693 * Able and willing to give written informed consent (informed consent is incorporated in the informed consent form of protocol P05693)
Exclusion criteria
* None
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Mothers With ≥1 Live Born Infant During Follow-up (Take-Home Baby Rate): Protocol Defined | From ≥10 weeks after bolus injection of hCG (administered in study P05693) up to time of birth on current follow-up study (up to 1 year) | The Take-Home Baby Rate was defined as the number of participants with an ongoing pregnancy in base study P05693 (NCT00697255) with at least one live born infant in the current follow-up study divided by the total number of participants treated in base study P05693. |
| Percentage of Mothers With ≥1 Live Born Infant During Follow-up (Take-Home Baby Rate): Alternate Analysis | From ≥10 weeks after bolus injection of hCG (administered in study P05693) up to time of birth on current follow-up study (up to 1 year) | Take-Home Baby Rate was alternately defined ad hoc as the number of participants with an ongoing pregnancy in base study P05693 (NCT00697255) with at least one live born infant in the current follow-up study divided by the total number of participants who received bolus injection of hCG in the base study. |
| Number of Mothers With Adverse Events (AEs) During Follow-up | From ≥10 weeks after bolus injection of hCG (administered in study P05693) up to 1 day after birth on current follow-up study (up to 1 year) | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. |
| Number of Mothers With Serious AEs (SAEs) During Follow-up | From ≥10 weeks after bolus injection of hCG (administered in study P05693) up to 1 day after birth on current follow-up study (up to 1 year) | An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. |
| Number of Infants With AEs During Follow-up | From ≥10 weeks after bolus injection of hCG (administered in study P05693) up to 12 weeks after birth on current follow-up study | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. |
| Number of Infants With SAEs During Follow-up | From ≥10 weeks after bolus injection of hCG (administered in study P05693) up to 12 weeks after birth on current follow-up study | An SAE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. |
Participant flow
Recruitment details
Participants treated with either corifollitropin alfa + recombinant Follicular Stimulating Hormone (recFSH) or corifollitropin alfa + Human Chorion Gonadotropin (hCG) in P05693 (NCT00697255) and with an ongoing pregnancy were to be recruited for the following study.
Pre-assignment details
Of 8 participants treated with corifollitropin alfa + recFSH (5) or hCG (3) in base study P05693 (NCT00697255), one participant from the corifollitropin alfa + hCG group was enrolled in the current follow-up study with an ongoing multiple pregnancy. No participants from the corifollitropin alfa + recFSH group enrolled in the current follow-up study
Participants by arm
| Arm | Count |
|---|---|
| Corifollitropin Alfa + hCG Mothers Eligible participants in Stage 1b of base study P05693 (NCT00697255) were administered injection(s) with SC corifollitropin alfa (30 mcg) and daily SC injections with hCG (200 IU) when the largest follicle reached a size of ≥12 mm. A bolus injection of hCG (5000 IU) was then administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed. Eligible mothers in this group with an ongoing pregnancy established in the base study (confirmed at ≥10 weeks after hCG bolus injection) were then followed for safety and efficacy on the current FU study (P05713) according to standard practice (no treatment administered). | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Corifollitropin Alfa + hCG Mothers |
|---|---|
| Age, Continuous | 31 years STANDARD_DEVIATION 0 |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 1 | 0 / 2 |
| serious Total, serious adverse events | 1 / 1 | 2 / 2 |
Outcome results
Primary
Number of Infants With AEs During Follow-up
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time frame: From ≥10 weeks after bolus injection of hCG (administered in study P05693) up to 12 weeks after birth on current follow-up study
Population: Follow-up safety analysis was performed on the fetuses/infants delivered by the one expectant mother who received corifollitropin alfa + hCG on the base study P05693 (NCT00697255) and who enrolled on the follow-up study. There were no other eligible infants to be evaluated for safety.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Corifollitropin Alfa + recFSH Mothers | Number of Infants With AEs During Follow-up | 2 participant |
Primary
Number of Infants With SAEs During Follow-up
An SAE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
Time frame: From ≥10 weeks after bolus injection of hCG (administered in study P05693) up to 12 weeks after birth on current follow-up study
Population: Follow-up safety analysis was performed on the fetuses/infants delivered by the one expectant mother who received corifollitropin alfa + hCG on the base study P05693 (NCT00697255) and who enrolled on the follow-up study. There were no other eligible infants to be evaluated for safety.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Corifollitropin Alfa + recFSH Mothers | Number of Infants With SAEs During Follow-up | 2 participants |
Primary
Number of Mothers With Adverse Events (AEs) During Follow-up
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time frame: From ≥10 weeks after bolus injection of hCG (administered in study P05693) up to 1 day after birth on current follow-up study (up to 1 year)
Population: Follow-up safety analysis was performed on the one expectant mother who received corifollitropin alfa + hCG on the base study P05693 (NCT00697255) and who enrolled on the follow-up study. No mothers receiving corifollitropin alfa + recFSH in the base study were enrolled in this follow-up study or included in safety analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Corifollitropin Alfa + hCG Mothers | Number of Mothers With Adverse Events (AEs) During Follow-up | 1 participants |
Primary
Number of Mothers With Serious AEs (SAEs) During Follow-up
An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect.
Time frame: From ≥10 weeks after bolus injection of hCG (administered in study P05693) up to 1 day after birth on current follow-up study (up to 1 year)
Population: Follow-up safety analysis was performed on the one expectant mother who received corifollitropin alfa + hCG on the base study P05693 (NCT00697255) and who enrolled on the follow-up study. No mothers receiving corifollitropin alfa + recFSH in the base study were enrolled in this follow-up study or included in safety analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Corifollitropin Alfa + hCG Mothers | Number of Mothers With Serious AEs (SAEs) During Follow-up | 1 participants |
Primary
Percentage of Mothers With ≥1 Live Born Infant During Follow-up (Take-Home Baby Rate): Alternate Analysis
Take-Home Baby Rate was alternately defined ad hoc as the number of participants with an ongoing pregnancy in base study P05693 (NCT00697255) with at least one live born infant in the current follow-up study divided by the total number of participants who received bolus injection of hCG in the base study.
Time frame: From ≥10 weeks after bolus injection of hCG (administered in study P05693) up to time of birth on current follow-up study (up to 1 year)
Population: Participants in the Intent-to-Treat group (ITT) in base study P05693 (NCT00697255) that received bolus injection of hCG.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Corifollitropin Alfa + recFSH Mothers | Percentage of Mothers With ≥1 Live Born Infant During Follow-up (Take-Home Baby Rate): Alternate Analysis | 0.0 percentage of participants |
| Corifollitropin Alfa + hCG Mothers | Percentage of Mothers With ≥1 Live Born Infant During Follow-up (Take-Home Baby Rate): Alternate Analysis | 100.0 percentage of participants |
Primary
Percentage of Mothers With ≥1 Live Born Infant During Follow-up (Take-Home Baby Rate): Protocol Defined
The Take-Home Baby Rate was defined as the number of participants with an ongoing pregnancy in base study P05693 (NCT00697255) with at least one live born infant in the current follow-up study divided by the total number of participants treated in base study P05693.
Time frame: From ≥10 weeks after bolus injection of hCG (administered in study P05693) up to time of birth on current follow-up study (up to 1 year)
Population: Intent-to-Treat group (ITT) consisted of all treated participants in base study P05693 (NCT00697255): 5 participants in Stage Ia and 3 participants in Stage Ib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Corifollitropin Alfa + recFSH Mothers | Percentage of Mothers With ≥1 Live Born Infant During Follow-up (Take-Home Baby Rate): Protocol Defined | 0.0 percentage of participants |
| Corifollitropin Alfa + hCG Mothers | Percentage of Mothers With ≥1 Live Born Infant During Follow-up (Take-Home Baby Rate): Protocol Defined | 33.3 percentage of participants |