Safety Study for Prospective Assessment of Pregnancy Outcomes in Patients Treated With Tildrakizumab

Study Overview
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Brief Summary
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This study will utilize a prospective, observational, exposure cohort design to examine pregnancy and infant outcomes in women and infants who are exposed to tildrakizumab during pregnancy to treat an approved indication. The pregnancy registry cohort study will be conducted by the Organization of Teratology Information Specialists (OTIS), which is a network of university and health department based information centers serving pregnant women and healthcare providers throughout North America. These services provide a basis for collaborative research such as this Registry. These Services located throughout the United States (US) and Canada will serve as a source of referrals not only for tildrakizumab-exposed pregnancies but also for similarly ascertained disease-matched comparison pregnant women who have not used tildrakizumab in pregnancy. The target follow-up period will be until end of pregnancy and 1 year of age for live born infants.

Official Title
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Post-authorization Safety Study for Assessment of Pregnancy Outcomes in Patients Treated With Tildrakizumab

Conditions
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Pregnancy Related

Intervention / Treatment
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* Drug: Pregnant women exposed to tildrakizumab
* Drug: Pregnant women not exposed to tildrakizumab


Participation Criteria
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Eligibility Criteria
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Cohort 1: Tildrakizumab-Exposed Cohort Pregnant women Exposure to tildrakizumab for the treatment of an approved indication, for any number of days, at any dose, and at any time from the first day of the last menstrual period up to and including the end of pregnancy Agree to the conditions and requirements of the study including the interview schedule, and release of medical records Cohort 2: Disease-Matched Comparison Cohort Pregnant women Diagnosed with a tildrakizumab-approved indication; frequency matched to the exposed group by disease indication, with the indication validated by medical records when possible No exposure to tildrakizumab at any time in the current pregnancy; may or may not have taken another medication for their disease in the current pregnancy Agree to the conditions and requirements of the study including the interview schedule, and release of medical records Exclusion criteria: Cohort 1: Tildrakizumab-Exposed Cohort: Women who have first contact with the project after prenatal diagnosis of any major structural defect Women who have enrolled in the tildrakizumab cohort study with a previous pregnancy (women may only enroll once in the Tildrakizumab Pregnancy Study) Women who have used tildrakizumab for an indication other than a currently approved indication Retrospective enrollment after the outcome of pregnancy is known Cohort 2: Disease-Matched Comparison Cohort Women who have first contact with the project after prenatal diagnosis of any major structural defect Exposure to tildrakizumab anytime during the current pregnancy Women who have enrolled in the tildrakizumab cohort study with a previous pregnancy (women may only enroll once in the Tildrakizumab Pregnancy Study) Retrospective enrollment after the outcome of pregnancy is known
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Tildrakizumab-Exposed Cohort<br>Exposure to tildrakizumab for the treatment of an approved indication | Drug: Pregnant women exposed to tildrakizumab<br>* Subjects exposure to tildrakizumab for the treatment of an approved indication, for any number of days, at any dose, and at any time from the first day of the last menstrual period (LMP) up to and including the end of pregnancy<br>|
| Disease-Matched Comparison Cohort<br>No exposure to tildrakizumab at any time in the current pregnancy | Drug: Pregnant women not exposed to tildrakizumab<br>* Subjects diagnosed with a tildrakizumab-approved indication; frequency matched to the exposed group by disease indication, with the indication validated by medical records when possible, and Subjects with no exposure to tildrakizumab at any time in the current pregnancy; may or may not have taken another medication for their disease in the current pregnancy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major structural defects in children | defined and classified using the US Centers for Disease Control and Prevention (CDC) coding manual that is used for the Metropolitan Atlanta Congenital Defects Program (MACDP) classification of major structural defects | Up to 1 year of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spontaneous abortion/miscarriage | defined as non-deliberate fetal death that occurs prior to 20.0 weeks post-last menstrual period | 20 weeks post-last menstrual period | 
| Stillbirth | defined as non-deliberate fetal death anytime in gestation at or after 20.0 weeks post-last menstrual period | from 20 weeks post-last menstrual period to end of pregnancy | 
| Elective termination/abortion | defined as deliberate discontinuation of pregnancy through medication or surgical procedures | At the end of pregnancy or through 9 month pregnancy period | 
| neonatal/infant death | defined as any death in a live born infant during the first 6 months of age | 6 months of age | 
| Small for gestational age | defined as birth size (weight, length, or head circumference) less than or equal to the 10th centile for sex and gestational age using standard pediatric CDC growth curves for full term or preterm infants | at birth | 
| Postnatal growth deficiency | defined as postnatal size (weight, length or head circumference) less than or equal to the 10th centile for sex and age using standard pediatric growth curves and adjusted for postnatal age for premature infants if the postnatal measurement is obtained at less than 1 year of age | Up to 1 year of age | 
| Malignancies in live born children | defined as any malignancy reported in an infant within the first year of life | Up to 1 year of age | 
| Hospitalization in live born children | defined as any hospitalization of the infant within the first year of life after discharge following delivery | Up to 1 year of age | 
| Postnatal serious or opportunistic infection in live born children | defined as any infection resulting in hospitalization, X-ray proven pneumonia, neonatal sepsis, meningitis, osteomyelitis, bacteremia, septic arthritis, abscess, mycobacteria infections, invasive fungal infection including histoplasmosis, coccidiomycosis, candidiasis, aspergillosis, and blastomycosis, pneumocystis jirovecii infection, systemic cytomegalovirus, herpes zoster and herpes simplex infection, listeria infections, and Legionella infection. | Up to 1 year |