An Observational Study on Sarilumab-exposed Pregnancies

Kevzara® (Sarilumab) Pregnancy Exposure Registry: An OTIS Pregnancy Surveillance Study

Primary Objective:

To evaluate the relative risk of major structural birth defects, specifically a pattern of anomalies, in sarilumab-exposed pregnancies compared to disease-matched unexposed pregnancies.

Secondary Objective:

To evaluate the risk for sarilumab-exposure relative to the group of healthy pregnant women, and the effect of exposure on other adverse pregnancy and infants outcomes.

Study Overview

• Status: Active, not recruiting
• Conditions: Rheumatoid Arthritis -Exposure During Pregnancy
• Intervention / Treatment: Drug: Sarilumab SAR153191 (REGN88)

Detailed Description

Pregnant women enrolled in the study will participate for the duration of that pregnancy. Those who deliver at least one live born infant and the infants will participate for 1 year after delivery of that infant.

• Study Type: Observational
• Enrollment (Actual): 113

Contacts and Locations

Study Locations

• Canada
  • Canada, Canada
    • Canada
• United States
  • New York
    • New York, New York, United States, 00000
      • United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Pregnant women enrolled in the study will participate for the duration of that pregnancy. Those who deliver at least one live born infant and the infants will participate for 1 year after delivery of that infant.

Description

Inclusion criteria:

• Cohort 1: Sarilumab-Exposed Cohort
• Currently pregnant, exposed to Kevzara (sarilumab) for approved indication
• Cohort 2: Disease-matched Comparison Cohort
• Currently pregnant, diagnosed with Kevzara (sarilumab) approved indication
• Cohort 3: Non-diseased Comparison Cohort
• Currently pregnant, not diagnosed with a Kevzara (sarilumab) indication and unexposed to Kevzara

Exclusion criteria:

First contact the Registry after prenatal diagnosis of any major structural defect or after pregnancy outcome is known (retrospective data).

Enrolled in this cohort study with a previous pregnancy. Cohort 1: Sarilumab-Exposed Cohort

• Exposed to Kevzara (sarilumab) for an indication other than a currently approved indication.
• Exposure to another biologic during pregnancy or within 10 weeks prior to the first day of LMP.
• Exposed to methotrexate, cyclophosphamide, chlorambucil, or mycophenolate mofetil in pregnancy (ie, at any time after the LMP), or leflunomide within two years prior to pregnancy unless a blood level for leflunomide below 0.02 mcg/mL has been documented prior to LMP before the pregnancy.
• Cohort 2: Disease-matched Comparison Cohort
• Exposure to any Kevzara (sarilumab) during pregnancy or within 10 weeks prior to the first day of the LMP.
• Exposed to methotrexate, cyclophosphamide, chlorambucil, or mycophenolate mofetil in pregnancy (ie, at any time after the LMP), or leflunomide within two years prior to pregnancy unless a blood level for leflunomide below 0.02 mcg/mL has been documented prior to LMP before the pregnancy.
• Cohort 3: Non-diseased Comparison Cohort
• Diagnosed for any serious chronic disease that is thought to adversely impact pregnancy.
• Exposed to a known human teratogen during pregnancy as confirmed by the OTIS Research Center

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1; Sarilumab-Exposed Cohort: Pregnant women exposed to Kevzara (sarilumab) for the treatment of an approved Kevzara (sarilumab) 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	Drug: Sarilumab SAR153191 (REGN88); Pharmaceutical form:injection Route of administration: subcutaneous; Other Names: Kevzara
Cohort 2; Disease-matched Comparison Cohort: Pregnant women diagnosed with Kevzara (sarilumab) approved indication. Approximate frequency matched to the exposed group by disease indication, validated by medical records, who have not been exposed to Kevzara (sarilumab) any time in the current pregnancy, and have taken another biologic DMARD medication for their disease within 2 years before the current pregnancy and have an indication for such treatment at enrollment
Cohort 3; Non-diseased Comparison Cohort: Healthy pregnant women not diagnosed with a Kevzara (sarilumab) indication and unexposed to Kevzara (sarilumab) during the course of the pregnancy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of major structural birth defect	A major structural birth defect is a defect that has either cosmetic or functional significance to the child (eg, a cleft lip) and is identified up to one year of age by the mother, the health care provider/medical record, or identified in the dysmorphological examination.	Up to 1 year of age of the infant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pregnancy Outcomes: Spontaneous abortion	Spontaneous abortion is defined as non-deliberate embryonic or fetal death that occurs < 20.0 weeks' gestation post-LMP (Last Menstrual period).	Date of conception to 20 weeks gestation
Pregnancy Outcomes: Stillbirth	Stillbirth is defined as a non-deliberate fetal death that occurs at or after 20 weeks of gestation but prior to delivery.	After 20 weeks of gestation but prior to delivery
Pregnancy Outcomes: Premature delivery	Premature delivery is defined as live birth prior to 37 weeks' gestation as counted from LMP (Last Menstrual period).	Live birth prior to 37 weeks gestation
Infant Outcomes: pattern of minor structural birth defects	A specific pattern of 3 or more structural defects in live born infants with dysmorphological physical examination.	Up to 1 year of age of the infant
Infant Outcomes: Small for gestational age	Proportion of infants less than or equal to the 10th percentile for sex and gestational age on weight, length, or head circumference.	At birth
Infant Outcomes: Postnatal growth deficiency	Proportion of infants less than or equal to the 10th percentile for sex and age on weight, length, or head circumference at 1 year postnatal evaluation.	Up to 1 year of age of the infant
Infant Outcomes: Serious or opportunistic infections	Proportion of infants who experienced serious or opportunistic infections up to 1 year of age.	Up to 1 year of age of the infant
Infant Outcomes: Hospitalizations	Proportion of infants who experienced hospitalizations in the first year of life excluding those that are linked to premature delivery or birth defects included as endpoints.	Up to 1 year of age of the infant
Infant Outcomes: Malignancies	Proportion of infants who reported malignancies reported in an infant after birth and up to 1 year of age.	Up to 1 year of age of the infant -

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2018
• Primary Completion (Anticipated): February 8, 2024
• Study Completion (Anticipated): February 8, 2024

Study Registration Dates

• First Submitted: December 15, 2017
• First Submitted That Met QC Criteria: December 15, 2017
• First Posted (Actual): December 19, 2017

Study Record Updates

• Last Update Posted (Actual): December 2, 2022
• Last Update Submitted That Met QC Criteria: December 1, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: OBS15155; U1111-1200-1947 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No