An Observational Study on Teriflunomide-exposed Pregnancies

• ClinicalTrials.gov Identifier: NCT03198351
• Recruitment Status: Recruiting
• First Posted: June 26, 2017
• Last Update Posted: January 9, 2023
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Multiple Sclerosis	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 Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 325 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Target Follow-Up Duration: 2 Years
• Official Title: Teriflunomide Pregnancy Outcome Exposure Registry: An OTIS Autoimmune Diseases in Pregnancy Project
• Actual Study Start Date: April 25, 2013
• Estimated Primary Completion Date: July 3, 2023
• Estimated Study Completion Date: July 3, 2023

Groups and Cohorts

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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. Rate of major structural defects in live born infants [ Time Frame: Up to the infant's first year birthday ]

Secondary Outcome Measures :

1. Proportion of major structural defects in all pregnancies [ Time Frame: up to 1 year of age in infant ]
2. Specific pattern of 3 or more minor structural defects in live born infants receiving the exam [ Time Frame: up to one year after birth ]
3. Rate of spontaneous abortion [ Time Frame: date of conception to 20 weeks gestation ]
4. Rate of preterm delivery [ Time Frame: live birth prior to 37 weeks gestation ]
5. 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 [ Time Frame: at birth ]
6. 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 [ Time Frame: 1 year ]

Eligibility Criteria

• Ages Eligible for Study: 16 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: Female
• 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.

Criteria

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.

Contacts and Locations

Contacts

Contact: Trial Transparency email recommended (Toll free number for US & Canada); 800-633-1610 ext 1 then #; Contact-US@sanofi.com

Locations

United States, California

University of California at San Diego-Site Number:001; Recruiting

San Diego, California, United States, 92093

Canada

Investigational Site Number :002; Recruiting

Canada, Canada

Sponsors and Collaborators

Sanofi

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

Additional Information:

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT03198351
• Other Study ID Numbers: OBS13499; U1111-1183-8711 ( Other Identifier: UTN )
• First Posted: June 26, 2017
• Last Update Posted: January 9, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Teriflunomide; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors