RAPA-501-ALS is an Intermediate-Size Expanded Access Trial of RAPA-501 autologous hybrid TREG/Th2 cells in patients living with amyotrophic lateral sclerosis (pwALS).
This is an open-label, non-randomized, multi-center intermediate size expanded access
clinical trial of single-agent RAPA-501 cells in patients with high-risk ALS who are not
eligible for other ALS clinical trials.
After a subject consents to the study, an apheresis procedure will be performed to collect
cells to manufacture the investigational product, RAPA-501 T cells. RAPA-501 cells are
manufactured ex vivo using epigenetic reprogramming to yield a T cell population that is
enriched for a dual anti-inflammatory phenotype based on hybrid TREG and Th2 differentiation.
RAPA-501 cells express both the TREG and Th2 transcription factors FOXP3 and GATA3, are
enriched for expression of the ATP ectonucleotidase molecules CD39 and CD73, are enriched for
the T cell homing molecule CD103, and suppress both effector T cell inflammatory molecules
and CNS microglial cell inflammatory molecules.
This study is evaluating RAPA-501 T cell therapy at the dose of 80 x 10EE6 cells per
infusion, with up to 4 infusions separated by six weeks between doses (infusion at time 0,
and then after week 6, 12, and 18). Study subjects are then followed for several months to
capture major clinical events and to assess survival. The total duration of RAPA-501 therapy
and follow-up interval on this protocol is approximately 8-months (250 days). The primary
objective in the expanded access cohort is to determine the feasibility and safety of the
highest-dose established safe dose of RAPA-501 (80 x 10 6 cells per infusion). Secondary
study objectives relate to determining the ALS disease activity pre-therapy, during study
interventions, and throughout the post-therapy observation interval of RAPA-501 therapy
through the monitoring of ALSFRS-R scores, SVC values, hand grip strength, and ROADS Scale.
In addition, secondary study objectives relate to characterizing immune system parameters
pre- and post- therapy and the potential effect of RAPA-501 therapy on serum markers of
neurodegeneration. To enhance an ability to determine potential efficacy, these parameters
will be compared to two comparator arms using machine learning algorithms developed by
Origent Data Sciences, namely: (1) a virtual intra-patient control cohort (patient serves as
own control); and (2) a comparator arm developed by prognostic mapping to the PRO-ACT
database.
Biological: RAPA-501 Autologous T cells
Experimental: Intermediate size expanded access cohort. Single-agent RAPA-501 T cells, 80 x 10EE6 cells per infusion.
Inclusion Criteria:
1. Male or female patients ≥ 18 years of age.
2. Patients with sporadic or familial amyotrophic lateral sclerosis (ALS) diagnosed as
laboratory-supported possible, probable, or definite according to World Federation of
Neurology El Escorial Criteria.
3. Pulmonary slow vital capacity (SVC) < 50% of predicted normal.
4. Must have a source of autologous T cells potentially sufficient to manufacture
RAPA-501 cells, as defined by a peripheral CD3+ T cell count ≥ 500 cells per μl.
5. Patients who are taking riluzole (Rilutek), edaravone (Radicava), and/or sodium
phenylbutyrate/taurursodial (Relyvrio) are eligible if taking the drug for at least 30
days prior to the screening visit.
6. Patients must be ≥ two (2) weeks removed from major surgery, or investigational
therapy.
7. Patients must have no ongoing, unstable serious illness other than ALS, as determined
by the Site Investigator.
8. Serum creatinine less than or equal to 2.0 mg/dL.
9. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit
of normal (ULN).
10. Bilirubin ≤ 1.5 (except if due to Gilbert's disease).
11. No history of abnormal bleeding tendency.
12. Voluntary written consent must be given before performance of any study related
procedure not part of standard medical care, with the understanding that consent may
be withdrawn by the patient at any time without prejudice to future medical care.
Exclusion Criteria:
1. Active uncontrolled infection.
2. Hypertension not adequately controlled by ≤ 3 medications.
3. History of documented pulmonary embolus within 6 months of enrollment.
4. Clinically significant cardiac pathology, as defined by: myocardial infarction within
6 months prior to enrollment, Class III or IV heart failure according to NYHA,
uncontrolled angina, severe uncontrolled ventricular arrhythmias, or
electrocardiographic evidence of acute ischemia or active conduction system
abnormalities.
5. HIV, hepatitis B, or hepatitis C seropositive.
6. Pregnant or breastfeeding subjects.
7. Subjects of childbearing age, or males who have a partner of childbearing potential,
who are unwilling to practice contraception.
8. Subjects may be excluded at the Principal Investigator discretion or if it is deemed
that allowing participation would represent an unacceptable medical or psychiatric
risk.
Massachusetts General Hospital
Boston, Massachusetts, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Daniel H Fowler; Chief Medical Officer, M.D.
301-518-3104
dan@rapatherapeutics.com
Jennifer L Sunga; Regulatory Affairs Associate
571-277-4916
jsunga@rapatherapeutics.com
Daniel H Fowler, M.D., Study Director
Rapa Therapeutics LLC