U01NS136022

Scalable expanded access with analysis of neurofilament and other biomarkers for ibudilast in ALS (SEA-NOBI-ALS) - Project summary/abstract

Current treatment options for amyotrophic lateral sclerosis (ALS) are inadequate, and many patients living with ALS seek access to experimental therapies with the hope that they will be effective.

Since most patients are excluded from participation in interventional trials based on restrictive inclusion and exclusion criteria, expanded access programs (EAPs) can bridge an important gap.

As such, through an EAP, we are now proposing to offer a promising drug – ibudilast – that is presently in a phase 2/3 trial for ALS.

Ibudilast has a well-established favorable safety record and has been approved for asthma and post-stroke symptoms in Japan.

Most relevant to our application is the fact that it is able to penetrate the central nervous system and has beneficial pharmacological effects for ALS, such as phosphodiesterase inhibition, increased autophagy, and amelioration of TDP-43 pathology.

This EAP will offer ibudilast as an experimental treatment to 200 ALS patients for 6 months.

Our project will develop a network of ALS physicians, to be managed by Mayo Clinic and WideTrial, which features self-activation and streamlined workflows with e-consent and enrollment, home-health visit ordering, drug supply ordering, and oversight of safety events and outcomes data capture.

Evaluations will be done either in a physician’s office or virtually in the patient’s home to minimize the burden of participation.

Safety monitoring will be conducted by the treating physician and through blood drawn in the patient’s home, processed in a central laboratory.

We will determine the effect of ibudilast on ALS progression using the gold standard primary clinical trial outcome measure – the ALS functional rating scale revised (ALSFRS-R) – with the emerging biomarker neurofilament light (NFL) as co-primary outcome.

Given the urgent need for reliable biomarkers, we will also test other candidates (e.g., TDP-43 markers).

Furthermore, to aid in differentiating between ibudilast responders and non-responders, we will use cutting-edge multi-omic sequencing methods.

Our usage of long-read whole-genome sequencing enables us to span the full range of genomic variation, and by generating complementary transcriptomic data, we can capture RNA signatures and disease-relevant cell populations.

Thus, we strongly believe that our datasets will provide a valuable resource and can possibly assist in patient stratification.

In summary, our EAP will offer a promising drug, bring together novel web-based infrastructures, implement novel biomarkers, and obtain multi-omic profiles of responders, thereby allowing tailored personalized therapies and setting the stage for future ALS clinical trials.

Mayo Clinic Jacksonville (A Nonprofit Corporation)

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM, RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS, RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS, IMPROVED METHODS OF DISEASE PREVENTION, NEW METHODS OF DIAGNOSIS AND TREATMENT, DRUG DEVELOPMENT, DEVELOPMENT OF NEURAL DEVICES, CLINICAL TRIALS, AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH, SYNAPSE FORMATION, FUNCTION, AND PLASTICITY, LEARNING AND MEMORY, CHANNELS, TRANSPORTERS, AND PUMPS, CIRCUIT FORMATION AND MODULATION, BEHAVIORAL AND COGNITIVE NEUROSCIENCE, SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION, NEUROENDOCRINE SYSTEMS, SLEEP AND CIRCADIAN RHYTHMS, AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE, TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM, NEURODEGENERATIVE DISORDERS, MOVEMENT DISORDERS, BRAIN TUMORS, CONVULSIVE DISORDERS, INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS, DISORDERS RELATED TO SLEEP, AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE NEUROSCIENCE WORKFORCE DEVELOPMENT, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM, TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.310 - Trans-NIH Research Support

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Jacksonville, Florida 322241865 United States

Single Zip Code

Amyotrophic Lateral Sclerosis (ALS) Intermediate Patient Population Expanded Access (U01 Clinical Trial Required) (RFA-NS-24-029)

Amendment Since initial award the total obligations have increased 93% from $6,133,297 to $11,846,278.