RAPA-501 Therapy for ALS Expanded Access Protocol

Phase 2

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Biological: RAPA-501 Autologous T cells

• Registration Number: NCT06169176
• Lead Sponsor: Rapa Therapeutics LLC

Brief Summary

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).

Detailed Description

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.

Study Timeline

• Study First Submitted: 2023-12-04
• Study First Submitted QC: 2023-12-04
• Study First Posted: 2023-12-13
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-13
• Last Update Posted: 2024-11-15

Recruitment & Eligibility

• Status: AVAILABLE
• Sex: All
• Target Recruitment: 40

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 (as measured within three months prior to screening or at the time of screening).
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.
13. Not enrolled in another interventional clinical trial or expanded access protocol and must have stopped taking other experimental drug(s) at least 2 weeks prior to screening.

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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.

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Study & Design

• Study Type: EXPANDED_ACCESS
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Biological: RAPA-501 Autologous T cells	RAPA-501 Autologous T cells	80 x 10\^6 cells per infusion; acceptable dose range of RAPA-501 is 20-to-80 x 10\^6 cells per infusion, depending on manufacturing yield

Primary Outcome Measures

Name	Time	Method
Safety	Entire Study	For patients with high-risk ALS who typically are not eligible for ALS clinical trials (defined in part by \<50% of predicted normal slow vital capacity \[SVC\]), evaluate the feasibility and safety of administering the highest established safe dose of RAPA-501 (80 x 106 cells per infusion; acceptable dose range of RAPA-501 is 20-to-80 x 106 cells per cycle, depending on manufacturing yield).

Trial Locations

Locations (9)

Providence Portland Medical Center; 🇺🇸 Portland, Oregon, United States

Barrow Neurological Institute; 🇺🇸 Phoenix, Arizona, United States

Mayo Clinic Hospital Phoenix; 🇺🇸 Scottsdale, Arizona, United States

University of California Irvine Health; 🇺🇸 Irvine, California, United States

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

University of Iowa Health Care; 🇺🇸 Iowa City, Iowa, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States