U01NS136020

Intermediate-size expanded access trial of autologous hybrid TREG/TH2 cell therapy (RAPA-501) of amyotrophic lateral sclerosis - ALS is a lethal neurodegenerative disease accelerated by neuroinflammation. Current FDA-approved therapies have modest benefits and do not address inflammation.

To address this, RAPA Therapeutics, LLC (RAPA) has developed an autologous T cell therapy (RAPA-501) that reduces inflammation, with the goal of reducing ALS morbidity and mortality. RAPA-501 are manufactured ex vivo to attain dual TREG/TH2 anti-inflammatory activity and a T-STEM phenotype that permits T cell therapy without conditioning chemotherapy.

In an ongoing clinical trial of RAPA-501 in people with ALS (PWALS) (NCT04220190), RAPA-501 cells were found to be safe (no product-related adverse events), biologically active (diverse anti-inflammatory effects in PWALS), and showed early trends toward stabilizing pulmonary function decline.

A phase 2/3 expansion cohort was added to the trial to assess whether RAPA-501 is efficacious in standard-risk PWALS. We will extend RAPA-501 therapy to PWALS not eligible for this ongoing phase 2/3 trial or other ALS trials, which nearly universally require that participants have a slow vital capacity (SVC) value of =50% of predicted normal.

The proposed EAP will enroll PWALS who have SVC values <50%. This population of PWALS is considered "high risk" (~50% chance of respiratory failure or death within 180 days) and thus particularly suitable for experimental immune therapies such as RAPA-501.

In addition, the RAPA-501-EAP will not exclude PWALS who have a prolonged time from ALS-related symptoms or low ALSFRS-R scores. Participants will receive four RAPA-501 IV infusions (every 42-days at established safe dose, 80 x 106 cells/infusion).

This RAPA-501-EAP will further evaluate the safety of this therapy, expand an understanding of the RAPA-501 therapeutic mechanism of action, and evaluate signals of efficacy in this real-world population of PWALS using standard methods and Origent Data Sciences machine learning ALS prediction algorithms.

The RAPA-501 EAP will be led by investigators at Mass General Hospital (MGH; Drs. Berry, Babu, and Paganoni) and sponsored by RAPA, which is responsible for RAPA-501 manufacturing and FDA regulatory filings under existing IND 019480 (Dr. Fowler, sponsor).

Clinical trial site investigators have experience with RAPA-501 therapy (MGH; Hackensack University Medical Center; and Mayo Clinic Arizona) or other cell therapies. Sites are geographically diverse and likely to accrue a significant number of underserved PWALS (U of Iowa; U of Idaho; Providence Hospital, Portland, Oregon; UC-Irvine; Columbia, NYC).

In addition, several research collaborations will emanate from the intensive study of the clinically-annotated, valuable research samples obtained from the RAPA-501 EAP.

The General Hospital 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]

Boston, Massachusetts 021142621 United States

Single Zip Code

Amyotrophic Lateral Sclerosis (ALS) Intermediate Patient Population Expanded Access (U01 Clinical Trial Required) (RFA-NS-23-012)

Amendment Since initial award the total obligations have increased 159% from $11,203,040 to $29,020,622.