Neoplasms

Symptoms and General Pathology

All Conditions

Nervous System Diseases

Immune System Diseases

Rare Diseases

Neoplasm Metastasis

Sclerosis

Multiple Sclerosis

Multiple Sclerosis, Chronic Progressive

Autoimmune Diseases

Demyelinating Autoimmune Diseases, CNS

Autoimmune Diseases of the Nervous System

Demyelinating Diseases

Neoplastic Processes

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Analgesics

Central Nervous System Depressants

All Drugs and Chemicals

Anti-Inflammatory Agents

Antirheumatic Agents

Morphine

Teriflunomide

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Immunosuppressive Agents

Immunologic Factors

* Participants will receive OL tolebrunitib 60 mg once daily.
* RMS participants who are not eligible for OL tolebrutinib per Health Authority and/or ethics committee decisions on the study conduct (ie, partial hold on initiation of tolebrutinib) will continue their parent study treatment assignment as per their randomization from the parent study.

* participants will receive teriflunomide 14 mg daily
* RMS participants who are not eligible for OL tolebrutinib per Health Authority and/or ethics committee decisions on the study conduct (ie, partial hold on initiation of tolebrutinib) will continue their parent study treatment assignment (either tolebrutinib or teriflunomide) as per their randomization from the parent study. If unblinded to teriflunomide parent study treatment assignment, these RMS participants will continue teriflunomide in the LTS17043 study.

Pharmaceutical form:Tablet-Route of administration:oral

Tolebrutinib

Placebo

Trial Transparency email recommended (Toll free for US & Canada)

This is a Phase 3 extension, global, multicenter study to assess the long-term safety and tolerability of tolebrutinib in adult participants (aged ≥18 years) with RMS, PPMS, or NRSPMS who were previously enrolled in the Phase 2b LTS (LTS16004) or 1 of the 4 Phase 3 tolebrutinib pivotal trials (GEMINI 1 \[EFC16033\], GEMINI 2 \[EFC16034\], HERCULES \[EFC16645\], or PERSEUS \[EFC16035\]).

SUBSTUDY: ToleDYNAMIC substudy

Participants with relapsing MS from the Phase 2b LTS16004 parent study will continue open-label (OL) tolebrutinib.

All participants from the Phase 3 parent studies (EFC16033, EFC16034, EFC16645, and EFC16035) will learn which treatment they received in the parent study:

* If from one of the Phase 3 relapsing MS studies and on teriflunomide, an accelerated elimination procedure or a 3-month washout period is required prior to starting OL tolebrutinib. If on teriflunomide, and benefiting and recommended by the Investigator, the participant may opt to continue teriflunomide outside of the LTS17043 study, if clinically appropriate. If on tolebrutinib, the participant will continue tolebrutinib.
* All participants from one of the Phase 3 progressive MS studies will start OL tolebrutinib.
* If a participant already started OL tolebrutinib in the Phase 3 parent study this will be continued.
* RMS participants who are not eligible for OL tolebrutinib per Health Authority and/or ethics committee decisions on the study conduct (ie, partial hold on initiation of tolebrutinib) will continue their parent study treatment assignment as per their randomization from the parent study.

The treatment duration per participant will be approximately 3 years of OL tolebrutinib.

A Study to Investigate Long-term Safety and Tolerability of Tolebrutinib in Participants With Multiple Sclerosis.

An Interventional, Phase 3 Extension Study to Investigate Long-term Safety and Tolerability of Tolebrutinib in Participants With Relapsing Multiple Sclerosis, Primary Progressive Multiple Sclerosis, or Nonrelapsing Secondary Progressive Multiple Sclerosis

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

Potentially clinically significant abnormalities (PCSAs) determined by laboratory tests, electrocardiogram (ECG), or vital signs and safety findings on MRI during the study period.

Time to onset is defined as a sustained increase from baseline EDSS (pivotal trial) of:

* RMS: ≥1.5 points when the baseline score is 0, ≥1.0 point when the baseline score is 0.5 to ≤5.5 or ≥0.5 point when the baseline score is \>5.5
* PPMS: ≥1.0 point when the baseline score is ≤5.5 or ≥0.5 point when the baseline score is \>5.5
* NRSPMS: ≥1.0 point when the baseline score is ≤5.0 or ≥0.5 point when the baseline score is \>5.0

ARR during the OL treatment period assessed by confirmed protocol-defined relapses

Sanofi

Skin and Connective Tissue Diseases

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Leflunomide

Enzyme Inhibitors

Women with HER2-negative metastatic and/or locally advanced, inoperable breast cancer.

Leflunomide tablet orally daily

Rita Vaccaro, RN

Joseph Sparano, MD

Triple negative breast cancer (TNBC) represents about 15% of breast cancers and is characterized by the lack of expression of estrogen receptor (ER), progesterone receptor (PR), and HER-2 non-amplification. Women with TNBC tend to be younger, African American, and BRCA-1 germline carriers. The hallmark of this subtype is early metastatic recurrences with a peak frequency 1-2 years. Prognosis for metastatic TNBC is especially poor with median survival of about 1 year as compared to about 2-4 years with other types of metastatic breast cancer.

The primary objective of the phase I part of this study is to determine the safety, tolerability and maximum tolerated dose of leflunomide in women with previously treated TNBC (or ER+ , HER2-neg MBC in Phase I). The primary objective of the phase 2 part of this study is to determine the efficacy of leflunomide in patients with TNBC.

Leflunomide, which will be taken daily by mouth, is an inhibitor of dihydroorotate dehydrogenase (DHODH). This proposal will test if DHODH is a novel target for a particular subset of women with metastatic TNBC.

Leflunomide in Previously Treated Metastatic Triple Negative Cancers

A Phase I/II Trial of Leflunomide in Women With Previously Treated Metastatic Triple Negative Cancers

3+3 escalation schema. Patients will be enrolled in escalating cohorts of 3 patients per dose level until Dose-limiting Toxicity (DLT) (defined as any grade 3 or higher toxicity seen during the first 3-week cycle of leflunomide). If 0 of 3 patients are observed to have a DLT, the next 3 patients will be enrolled in the next higher dose level cohort. If 2/3 patients experience a DLT, escalation will stop and the previous dose will be defined as the MTD. If 1/3 experiences a DLT, three additional patients will be enrolled at the same dose level. If ≤ 2/6 patients experience a DLT, the next cohort of three patients will be treated at the next dose level. If ≥ 3/6 experience a DLT, the next lower dose level will define the MTD. If at the 50 mg dose/day if 0/3 or ≤ 2/6 patients experience a DLT, then that dose will define the MTD

Response and progression to be evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST). CBR = Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) for at least 6 months duration

Number of side effects associated with oral leflunomide using NCI CTCAE v.4.03

Objective Response Rate (proportion of patients with the best overall response of CR or PR) in those who have measurable disease by RECIST

PFS of women with phosphatase and tensin homolog (PTEN) wild-type and PTEN null expression breast cancers. PFS is defined as the duration of time from the start of treatment to the first occurrence of disease progression or death from any cause, whichever occurs first.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Investigate Long-term Safety and Tolerability of Tolebrutinib in Participants With Multiple Sclerosis.	NCT06372145	Relapsing Multi... Secondary Progr... Progressive Rel...	Tolebrutinib Placebo Teriflunomide	18 Years -	Sanofi
Leflunomide in Previously Treated Metastatic Triple Negative Cancers	NCT03709446	Breast Neoplasm... Breast Diseases Metastatic Trip...	Leflunomide	18 Years -	Icahn School of Medicine at Mount Sinai
Leflunomide in Previously Treated Metastatic Triple Negative Cancers	NCT03709446	Breast Neoplasm... Breast Diseases Metastatic Trip...	Leflunomide	18 Years -	Icahn School of Medicine at Mount Sinai
A Study to Investigate Long-term Safety and Tolerability of Tolebrutinib in Participants With Multiple Sclerosis.	NCT06372145	Relapsing Multi... Secondary Progr... Progressive Rel...	Tolebrutinib Placebo Teriflunomide	18 Years -	Sanofi

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