A Study to Evaluate the Safety, Tolerability, Cellular Kinetics, and Pharmacodynamics of P-CD19CD20-ALLO1 in Participants With Multiple Sclerosis

Genentech

Status and phase: Begins enrollment in 1 month; Phase 1

Conditions: Multiple Sclerosis

Treatments: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: P-CD19CD20-ALLO1 Cells

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT07008378

GN45773

Details and patient eligibility

About

This study aims to explore the safety, tolerability, cellular kinetics, and pharmacodynamics of P-CD19CD20-ALLO1 in participants with progressive multiple sclerosis (PMS) and relapsing multiple sclerosis (RMS).

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age 18-60 years (inclusive) at the time of signing Informed Consent Form
• Diagnosis of progressive MS according to the revised McDonald 2017 criteria, and:

Expanded disability status scale (EDSS) score at screening, from 3 to 6 inclusive Evidence of disability progression and no relapses in the 2 years prior to screening

• Diagnosis of relapsing MS according to the revised McDonald 2017 criteria, and: Evidence of clinical relapses and MRI activity within two years prior to screening while on a disease modifying therapy

• EDSS score at screening, from 0 to 6 inclusive
• No relapses within 45 days of screening

Exclusion criteria

• Pregnant or breastfeeding, or intention of becoming pregnant within the timeframe in which contraception is required
• Participants who have confirmed or suspected Progressive Multifocal Leukoencephalopathy (PML)
• Known or suspected history of Hemophagocytic Lymphohistiocytosis/ Macrophage Activation Syndrome (HLH/MAS) or neurotoxicity with prior therapies
• Known presence of other neurologic disorders that may mimic MS
• History of currently active primary or secondary (non-drug-related) immunodeficiency
• Significant or uncontrolled medical disease which would preclude patient participation
• High risk for clinically significant bleeding or any condition requiring plasmapheresis, IV Ig, or acute blood product transfusions
• History of recurrent serious infections or chronic infection
• Prior treatment with CAR T-cell therapy, gene-therapy product, total body irradiation, bone marrow transplantation, allograft organ transplant, or hematopoietic stem cell transplant at any point
• Any previous treatment with immunomodulatory or immunosuppressive medication without an appropriate washout period.
• Inability to complete an MRI scan

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

---

60 participants in 1 patient group

Dose Escalation

Experimental group

Description:

Participants will receive a lymphodepleting chemotherapy regimen followed by a single infusion of P-CD19CD20-ALLO1. Dose escalation decisions will be made after participants are observed for a minimum of 28 days for toxicity.

Treatment:

Biological: P-CD19CD20-ALLO1 Cells

Drug: Fludarabine

Drug: Cyclophosphamide