An Observational Study on Teriflunomide-exposed Pregnancies

Teriflunomide Pregnancy Outcome Exposure Registry: An OTIS Autoimmune Diseases in Pregnancy Project

Primary Objective:

To evaluate any potential increase in the risk of major birth defects, in the first year of life, in teriflunomide-exposed pregnancies.

Secondary Objective:

To evaluate the potential effect of teriflunomide-exposure on other adverse pregnancy outcomes including any potential pattern of minor birth defects, spontaneous abortion, stillbirth, preterm delivery, small for gestational age at birth and at 1 year follow-up.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Teriflunomide (HMR1726)

Detailed Description

The total study duration per participant is approximately up to 2 years.

• This is a prospective, observational study (no intervention), ie, patient registry.
• The statistical analysis for the cohort study describe baseline characteristics in all three cohorts, and then will compare pregnancy outcomes in cohort 1 to cohort 2 and secondarily to cohort 3.
• For the "registry" group, without comparisons, only descriptive statistics of pregnancy outcomes will be summarized.

• Study Type: Observational
• Enrollment (Actual): 220

Contacts and Locations

Study Locations

• Canada
  • Canada, Canada
    • Investigational Site Number :002
• United States
  • California
    • San Diego, California, United States, 92093
      • University of California at San Diego-Site Number:001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

-Pregnant women will be enrolled at various stages of gestation depending when they are included in the registry; then the pregnant outcome will be followed and for live infants, the follow up will be up to the children's 1 year birthday.

Description

Inclusion criteria :

• Pregnant women who have provided an oral and/or written consent to enroll no later than 20 completed weeks from last menstrual period (LMP).
• Pregnant women who agree to the conditions and requirements of the study including the interview schedule, release of medical records, and the physical examination of live born infants (up to 1 year post birth).
• Pregnant women with a diagnosis of MS and teriflunomide exposure during pregnancy (Cohort 1).
• Pregnant women with MS but not exposed teriflunomide during pregnancy (Cohort 2).
• Healthy pregnant women who do not have a known diagnosis of MS and have no known exposure to a known human teratogen during pregnancy (Cohort 3).

Exclusion criteria:

• Pregnant women who come in first contact with the project after prenatal diagnosis of a major structural defect (Cohort 1, 2, 3). This does not apply to the "registry" group.
• Pregnant women who first come in contact with the project after 20 completed weeks' gestation (Cohort 1, 2, 3). This does not apply to the "registry" group.
• Pregnant women who had previously enrolled in the study for a previous pregnancy (only 1 pregnancy, per woman, maybe registered) (Cohort 1, 2, 3). This does not apply to the "registry" group.
• Retrospectively reported cases (Cohort 1, 2, 3). This does not apply to the "registry" group.
• Pregnant women with exposures to teriflunomide commencing after the 12th week post-LMP (Cohort 1). This does not apply to the "registry" group.
• Pregnant women who had previously been treated with teriflunomide if they had received any dose of the drug within 2 years prior to the index pregnancy and do not have documented blood levels below 0.02 mcg/mL prior to pregnancy (Cohort 2).

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

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort I; Pregnant women with a confirmed diagnosis of multiple sclerosis (MS) and teriflunomide exposure during the current pregnancy	Drug: Teriflunomide (HMR1726); Pharmaceutical form: tablet Route of administration: oral; Other Names: Aubagio
Cohort II; Pregnant women with MS not exposed to teriflunomide during the current pregnancy
Cohort III; Healthy pregnant women who do not have a known diagnosis of MS and have no known exposure to a known human teratogen
"Registry" group (not eligible for cohorts); Women who contact the OTIS registry study staff and who do not meet the criteria for the prospective study, for example, at time of contacting the study, having known prenatal diagnosis of congenital defect, or gestation weeks greater than 20 following a first trimester teriflunomide exposure, etc.; these participants will not be included in the primary analysis for the cohort study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of major structural defects in live born infants	Up to the infant's first year birthday

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of major structural defects in all pregnancies	up to 1 year of age in infant
Specific pattern of 3 or more minor structural defects in live born infants receiving the exam	up to one year after birth
Rate of spontaneous abortion	date of conception to 20 weeks gestation
Rate of preterm delivery	live birth prior to 37 weeks gestation
Proportion of infants who are small for gestational age (less than or equal to the 10th percentile for gestational age and sex) on weight, length, or head circumference	at birth
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	1 year

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2013
• Primary Completion (Actual): June 13, 2023
• Study Completion (Actual): June 13, 2023

Study Registration Dates

• First Submitted: June 22, 2017
• First Submitted That Met QC Criteria: June 22, 2017
• First Posted (Actual): June 26, 2017

Study Record Updates

• Last Update Posted (Actual): August 28, 2023
• Last Update Submitted That Met QC Criteria: August 25, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Teriflunomide
• Other Study ID Numbers: OBS13499; U1111-1183-8711 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

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