R01FD007275

Sirolimus TSC Epilepsy Prevention Study (STEPS) IND#145820
11/8/2019 - Summary/Abstract

Epilepsy is very prevalent and highly refractory to currently available medical treatments in Tuberous Sclerosis Complex (TSC), a genetic disorder affecting 1:6000 live births. Medically-refractory epilepsy in TSC is associated with lifelong intellectual disability and neurodevelopmental deficits.

Everolimus and sirolimus, pharmacological inhibitors of the mechanistic target of rapamycin complex 1 (mTORC1), have been successfully repurposed to treat many clinical manifestations of TSC, including focal-onset epilepsy. However, few patients become seizure-free following treatment with mTORC1 inhibitors, and 60% of patients with TSC are still in need of effective treatment.

Mouse models of TSC and human clinical trials indicate that early treatment with mTORC1 inhibitors, before the onset of seizures, may be a more effective treatment strategy against epilepsy and epilepsy-associated deficits in neurodevelopment in patients diagnosed with TSC.

The current study proposes a Phase IIB multicenter, randomized, double-blind, placebo-controlled clinical trial with sirolimus to test this hypothesis. The primary aims of the clinical trial are:

1. To demonstrate that sirolimus prevents or delays seizures in infants with TSC that are 0-12 months of age.
2. To demonstrate that sirolimus is safe and well-tolerated in infants with TSC that are 0-12 months of age.

Additional (secondary) aims of the trial are:

1. To demonstrate that early sirolimus treatment improves developmental delay, language impairment, adaptive skills, and autism risk.
2. To assess the utility of EEG and MRI biomarkers for measuring mTORC1 inhibition in the brain.
3. To validate precision dosing of sirolimus in infants with TSC.

Childrens Hospital Medical Center

TO ASSIST INSTITUTIONS AND ORGANIZATIONS, TO ESTABLISH, EXPAND, AND IMPROVE RESEARCH, DEMONSTRATION, EDUCATION AND INFORMATION DISSEMINATION ACTIVITIES, ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS), BIOLOGICS, BLOOD AND BLOOD PRODUCTS, THERAPEUTICS, VACCINES AND ALLERGENIC PROJECTS, DRUG HAZARDS, HUMAN AND VETERINARY DRUGS, CLINICAL TRIALS ON DRUGS AND DEVICES FOR ORPHAN PRODUCTS DEVELOPMENT, NUTRITION, SANITATION AND MICROBIOLOGICAL HAZARDS, MEDICAL DEVICES AND DIAGNOSTIC PRODUCTS, RADIATION EMITTING DEVICES AND MATERIALS, FOOD SAFETY AND FOOD ADDITIVES. THESE PROGRAMS ARE SUPPORTED DIRECTLY OR INDIRECTLY BY THE FOLLOWING CENTERS AND OFFICES: CENTER FOR BIOLOGICS EVALUATION AND RESEARCH (CBER), CENTER FOR DRUG EVALUATION AND RESEARCH (CDER), CENTER FOR DEVICES AND RADIOLOGICAL HEALTH (CDRH), CENTER FOR VETERINARY MEDICINE (CVM), CENTER FOR FOOD SAFETY AND APPLIED NUTRITION (CFSAN), NATIONAL CENTER FOR TOXICOLOGICAL RESEARCH (NCTR), THE OFFICE OF ORPHAN PRODUCTS DEVELOPMENT (OPD), THE CENTER FOR TOBACCO PRODUCTS (CTP), AND OFFICE OF REGULATORY AFFAIRS (ORA), AND THE OFFICE OF THE COMMISSIONER (OC). SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAMS: TO STIMULATE TECHNOLOGICAL INNOVATION, TO ENCOURAGE THE ROLE OF SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION BY MINORITY AND DISADVANTAGED PERSONS IN TECHNOLOGICAL INNOVATION. FUNDING SUPPORT FOR SCIENTIFIC CONFERENCES THAT ARE RELEVANT TO THE FDA SCIENTIFIC MISSION AND PUBLIC HEALTH ARE ALSO AVAILABLE.

93.103 - Food and Drug Administration Research

FDA Office of Acquisition and Grant Services (OAGS) [HHS - FDA]

Center for Tobacco Products (CTP) [HHS - FDA]

Cincinnati, Ohio 45229 United States

Single Zip Code

Clinical Studies of Orphan Products Addressing Unmet Needs of Rare Diseases (R01) Clinical Trials Required (RFA-FD-21-001)

Amendment Since initial award the End Date has been extended from 06/30/25 to 06/30/27 and the total obligations have increased 141% from $1,355,880 to $3,263,666.