NPER: Nplate® Pregnancy Exposure Registry

• Sponsor: Amgen (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02090088
• Collaborator: (none)
• Enrollment: 4
• Duration (Months): 56

Study Details

Study Description

Brief Summary

US study to estimate the prevalence at birth of major birth defects (ie, those that cause significant functional or cosmetic impairment, require surgery, or are life-limiting) in children born to mothers who have received Nplate® therapy at any time during the pregnancy.

Condition or Disease	Intervention/Treatment	Phase
Birth Defect; Spontaneous Abortions; Low Birth Weight	Drug: Not applicable- observational study

Detailed Description

The purpose of the NPER is to monitor pregnancies exposed to Nplate® and to detect and record serious adverse events in infants up to one year after birth. The lack of adequate human fetal safety data for Nplate® makes the NPER an important component of the pharmacovigilance program on the safety of this drug. With respect to fetal outcome, it is important to evaluate the spectrum of outcomes that may be relevant to a medication exposure during pregnancy, and these include both easily recognizable defects that are visible at birth, as well as more subtle or delayed defects that may not be readily identifiable without special expertise and observation beyond the newborn period.

Study Design

• Study Type: Observational [Patient Registry]
• Actual Enrollment: 4 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Nplate® Pregnancy Exposure Registry (NPER)
• Study Start Date: May 1, 2009
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
All Subjects All Subjects	Drug: Not applicable- observational study

Outcome Measures

Primary Outcome Measures

1. Number of Children Born With Major Birth Defects [At birth]

   An external, independent Congenital Malformation Adjudication Panel (CMAP) comprised of two clinical dysmorphologists and/or teratologists organized malformations based upon organ system and embryology, and determined whether structural defects were major or minor according to a modification of the Metropolitan Atlanta Congenital Defects Program (MACDP) birth defect classification system. A major structural defect is defined as a defect which has either cosmetic or functional significance to the child (eg, a cleft lip), require surgery, or are life-limiting).

Secondary Outcome Measures

1. Number of Children Born With Any 3 or More Minor Birth Defects [At birth]

   An external, independent Congenital Malformation Adjudication Panel (CMAP) comprised of two clinical dysmorphologists and/or teratologists organized malformations based upon organ system and embryology, and determined whether structural defects were major or minor according to a modification of the Metropolitan Atlanta Congenital Defects Program (MACDP) birth defect classification system. A minor structural defect is defined as a defect which occurs in less than 4% of the population but which has neither cosmetic nor functional significance to the child (eg, complete 2,3 syndactyly of the toes).

2. Number of Children Born With a Specific Pattern of Minor Birth Defects [At birth]

   Only those infants who have received medical evaluation and who have three or more minor defects will be considered "affected" for purposes of the evaluation of a pattern of minor defects.

3. Number of Participants With Spontaneous and Elective Abortions or Stillbirths [9 months (during pregnancy)]

   Number of each of spontaneous abortions, elective abortions, and stillbirths among mothers who received Nplate® therapy at any time during the pregnancy.

4. Number of Children With Preterm Birth or Low Birth Weight [At birth]

   Number of children with preterm birth (<37 weeks gestation) or low birth weight (<2,500 grams) among children born to mothers who have received Nplate® therapy at any time during the pregnancy.

5. Number of Children Born With Intrauterine Growth Restriction [At birth]

   Number of children born with intrauterine growth restriction (weight, length or head circumference less than tenth percentile for sex and gestational age) among mothers who have received Nplate® therapy at any time during the pregnancy.

6. Number of Infants With Adverse Events [12 months from birth]

   In the first year of life, the incidence of all serious adverse events, as well as of nevi (birthmarks) and angiomata (benign tumors with blood vessels or lymph vessels), among infants whose mothers received Nplate® therapy at any time during the pregnancy.

7. Number of Participants With Adverse Events [Throughout pregnancy and for up to 6 weeks after delivery]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Eligible subjects will be currently pregnant women residing in the US who: Have had any exposure to Nplate® at any time during the pregnancy, which is defined as the period between first day of the last menstrual period (LMP) (ie, within two weeks of conception) up to any date before the date of delivery or end of the pregnancy. The date of conception will be defined as fourteen days prior to the next expected menstrual period for women who report a regular menstrual cycle. If the date of the first day of the LMP is unclear, or if the estimated date of conception as determined by a first-trimester ultrasound differs by more than one week from the date as determined by the first day of LMP, the first-trimester ultrasound-derived date will be used to estimate the timing of exposure to Nplate®, as well as timing of enrollment. If neither a clear date of the first day of the LMP nor a first-trimester ultrasound is available, the estimated date of conception for purposes of enrollment will be determined by best estimate of the woman's prenatal care provider.

• Agree to enroll at any time from the estimated date of conception up to any date before the date of delivery or end of the pregnancy and who have not already had prenatal diagnosis of any major structural birth defect in the current pregnancy prior to enrollment.

• Agree to provide consent for participation in the registry including follow-up interviews.

Exclusion Criteria:

• Subjects will be ineligible for study participation if any of the following apply:

• Exposure to Nplate® did not occur during pregnancy.

• Prior knowledge of prenatal diagnosis of a birth defect. Patients who fall under this category will be encouraged to call the Amgen PSP toll free number for enrollment and follow-up.

• Cases reported to the NPER after completion of the exposed pregnancy. Patients who fall under this category will be encouraged to call the Amgen PSP toll free number for enrollment and follow-up.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT02090088
• Other Study ID Numbers: 20080046
• First Posted: Mar 18, 2014
• Last Update Posted: Jan 6, 2015
• Last Verified: Dec 1, 2014

• Additional relevant MeSH terms: Abortion, Spontaneous; Congenital Abnormalities; Birth Weight

Study Results

Participant Flow

Recruitment Details	The registry was initiated in May 2009. The first participant enrolled in June 2010 and the last participant enrolled in December 2013. Eligible participants were currently pregnant women residing in the United States who had any exposure to Nplate at any time during pregnancy.
Pre-assignment Detail	The Nplate® Pregnancy Exposure Registry (NPER) was to continue the follow-up of enrollees until April 2016; however, the NPER was terminated on 24 January 2014 because of the low number of participants enrolled.

Arm/Group Title	All Participants
Arm/Group Description	Pregnant woman who had any exposure to Nplate® at any time during pregnancy.
Period Title: Overall Study
STARTED	4
Gave Birth	4
COMPLETED	4
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Pregnant woman who had any exposure to Nplate® at any time during pregnancy.
Overall Participants	4
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	4 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Children Born With Major Birth Defects
Description	An external, independent Congenital Malformation Adjudication Panel (CMAP) comprised of two clinical dysmorphologists and/or teratologists organized malformations based upon organ system and embryology, and determined whether structural defects were major or minor according to a modification of the Metropolitan Atlanta Congenital Defects Program (MACDP) birth defect classification system. A major structural defect is defined as a defect which has either cosmetic or functional significance to the child (eg, a cleft lip), require surgery, or are life-limiting).
Time Frame	At birth

Outcome Measure Data

Analysis Population Description

Children born to enrolled participants during the study

Arm/Group Title	All Participants
Arm/Group Description	Pregnant woman who had any exposure to Nplate® at any time during pregnancy.
Measure Participants	4
Number [children]	0

2. Secondary Outcome

Title	Number of Children Born With Any 3 or More Minor Birth Defects
Description	An external, independent Congenital Malformation Adjudication Panel (CMAP) comprised of two clinical dysmorphologists and/or teratologists organized malformations based upon organ system and embryology, and determined whether structural defects were major or minor according to a modification of the Metropolitan Atlanta Congenital Defects Program (MACDP) birth defect classification system. A minor structural defect is defined as a defect which occurs in less than 4% of the population but which has neither cosmetic nor functional significance to the child (eg, complete 2,3 syndactyly of the toes).
Time Frame	At birth

Outcome Measure Data

Analysis Population Description

Children born to enrolled participants during the study

Arm/Group Title	All Participants
Arm/Group Description	Pregnant woman who had any exposure to Nplate® at any time during pregnancy.
Measure Participants	4
Number [children]	0

3. Secondary Outcome

Title	Number of Children Born With a Specific Pattern of Minor Birth Defects
Description	Only those infants who have received medical evaluation and who have three or more minor defects will be considered "affected" for purposes of the evaluation of a pattern of minor defects.
Time Frame	At birth

Outcome Measure Data

Analysis Population Description

Children born with 3 or more minor birth defects

Arm/Group Title	All Participants
Arm/Group Description	Pregnant woman who had any exposure to Nplate® at any time during pregnancy.
Measure Participants	0

4. Secondary Outcome

Title	Number of Participants With Spontaneous and Elective Abortions or Stillbirths
Description	Number of each of spontaneous abortions, elective abortions, and stillbirths among mothers who received Nplate® therapy at any time during the pregnancy.
Time Frame	9 months (during pregnancy)

Outcome Measure Data

Analysis Population Description

All enrolled participants

Arm/Group Title	All Participants
Arm/Group Description	Pregnant woman who had any exposure to Nplate® at any time during pregnancy.
Measure Participants	4
Spontaneous abortions	0 0%
Elective abortions	0 0%
Stillbirths	0 0%

5. Secondary Outcome

Title	Number of Children With Preterm Birth or Low Birth Weight
Description	Number of children with preterm birth (<37 weeks gestation) or low birth weight (<2,500 grams) among children born to mothers who have received Nplate® therapy at any time during the pregnancy.
Time Frame	At birth

Outcome Measure Data

Analysis Population Description

Children born to enrolled participants during the study

Arm/Group Title	All Participants
Arm/Group Description	Pregnant woman who had any exposure to Nplate® at any time during pregnancy.
Measure Participants	4
Preterm birth	1
Low birth weight	1

6. Secondary Outcome

Title	Number of Children Born With Intrauterine Growth Restriction
Description	Number of children born with intrauterine growth restriction (weight, length or head circumference less than tenth percentile for sex and gestational age) among mothers who have received Nplate® therapy at any time during the pregnancy.
Time Frame	At birth

Outcome Measure Data

Analysis Population Description

Children born to enrolled participants during the study

Arm/Group Title	All Participants
Arm/Group Description	Pregnant woman who had any exposure to Nplate® at any time during pregnancy.
Measure Participants	4
Number [children]	1

7. Secondary Outcome

Title	Number of Infants With Adverse Events
Description	In the first year of life, the incidence of all serious adverse events, as well as of nevi (birthmarks) and angiomata (benign tumors with blood vessels or lymph vessels), among infants whose mothers received Nplate® therapy at any time during the pregnancy.
Time Frame	12 months from birth

Outcome Measure Data

Analysis Population Description

Children born to enrolled participants during the study

Arm/Group Title	All Participants
Arm/Group Description	Pregnant woman who had any exposure to Nplate® at any time during pregnancy.
Measure Participants	4
Serious adverse events	2
Nevi	0
Angiomata	0

8. Secondary Outcome

Title	Number of Participants With Adverse Events
Time Frame	Throughout pregnancy and for up to 6 weeks after delivery

Outcome Measure Data

Analysis Population Description

All enrolled participants

Arm/Group Title	All Participants
Arm/Group Description	Pregnant woman who had any exposure to Nplate® at any time during pregnancy.
Measure Participants	4
Number [participants]	4 100%

Adverse Events

Time Frame	Women were assessed during pregnancy (up to 9 months) and up to 6 weeks after delivery; Infants were assessed for up to 1 year after birth.
Arm/Group Title	All Participants		Infants
Arm/Group Description	Pregnant woman who had any exposure to Nplate® at any time during pregnancy.		Infants who were born to enrolled participants during the study.
All Cause Mortality
	All Participants		Infants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	All Participants		Infants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		2/4 (50%)
Blood and lymphatic system disorders
Thrombocytopenia	1/4 (25%)		1/4 (25%)
Thrombocytosis	1/4 (25%)		0/4 (0%)
Haemorrhagic diathesis	0/4 (0%)		1/4 (25%)
Congenital, familial and genetic disorders
Phimosis	0/4 (0%)		1/4 (25%)
Endocrine disorders
Adrenal Insufficiency	0/4 (0%)		1/4 (25%)
General disorders
Therapeutic response decreased	1/4 (25%)		0/4 (0%)
Hepatobiliary disorders
Jaundice	0/4 (0%)		1/4 (25%)
Injury, poisoning and procedural complications
Exposure to communicable disease	1/4 (25%)		0/4 (0%)
Investigations
Platelet count decreased	2/4 (50%)		1/4 (25%)
Nervous system disorders
Intraventricular Haemorrhage	0/4 (0%)		1/4 (25%)
Pregnancy, puerperium and perinatal conditions
Placental Infarction	1/4 (25%)		0/4 (0%)
Premature Delivery	1/4 (25%)		0/4 (0%)
Premature baby	0/4 (0%)		1/4 (25%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/4 (25%)		0/4 (0%)
Surgical and medical procedures
Caesarean section	1/4 (25%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	All Participants		Infants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/4 (0%)

Limitations/Caveats

The number of infants born to participants was too low to draw conclusions or make comparisons to the Systematic Tracking of Real Kids (STORK) analysis or to the background rates of congenital anomalies or preterm infants in the general population.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.