US Zamto-cel Autoimmune Diseases

NCT06708845 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: M-2024-423
• Study Type: interventional
• Target: 48
• Locations: 0 countries
• Sites: N/A

Brief Summary

AID is a phase I multi-cohort study to assess the safety and tolerability of zamtocabtagene autoleucel (zamto-cel) in patients with refractory autoimmune diseases (SLE-Non renal, SLE-LN, SSc/dcSSc) after receiving standard therapy.

Conditions

Lupus Nephritis; Systemic Lupus Erythematosus; Systemic Sclerosis (SSc); Diffuse Cutaneous Systemic Sclerosis

Keywords

Chimeric antigen receptor; CAR T; Zamtocabtagene autoleucel; Autoimmune Disease; Immune System Diseases; SLE-Non renal; SLE-LN; SSc; dcSSc; Lupus

Outcome Measures

Primary Outcomes (2)

• The incidence and severity of adverse events (AEs), adverse events of special interest (AESIs), and serious adverse events (SAEs)

  From enrollment through study completion 12 months post zamto-cel infusion

• The proportion of subjects with dose-limiting toxicities (DLTs) up to Day 28 and determination of recommended Phase 2 dose (RP2D)

  From enrollment through Day 28 post zamto-cel infusion

Secondary Outcomes (4)

• The incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)

  From enrollment through study completion 12 months post zamto-cel infusion

• Clinical response at Week 4, 12, 24, and 52 evaluated by defined disease-specific activity measures in SLE-Non renal, SLE-LN, and SSc/dcSSc

  From enrollment through study completion 12 months post zamto-cel infusion

• The duration of remission or low disease activity status in respective diseases under the study

  From enrollment through study completion 12 months post zamto-cel infusion

• Persistence, maximal drug concentration (Cmax), time to reach Cmax, area under the concentration curve, and phenotype of zamto-cel

  From enrollment through study completion 12 months post zamto-cel infusion

Study Arms (2)

Dose Level 1

EXPERIMENTAL

Biological: zamtocabtagene autoleucel; Drug: Cyclophosphamide; Drug: Fludarabine

Dose Level 2

EXPERIMENTAL

Biological: zamtocabtagene autoleucel; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

zamtocabtagene autoleucel BIOLOGICAL

chimeric antigen receptor T-cell (CAR-T) therapy

Dose Level 1; Dose Level 2

Cyclophosphamide DRUG

Lymphodepleting chemotherapy

Dose Level 1; Dose Level 2

Fludarabine DRUG

Lymphodepleting chemotherapy

Dose Level 1; Dose Level 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Confirmed diagnosis of autoimmune disease (SLE-Non-renal, SLE-LN, SSc/ dcSSc)
• Prior gene therapy treatment
• Active malignancy within past 5 years
• Significant active fungal or bacterial infection
• History or presence of CNS lupus or other CNS disease
• eGFR \< 45 mL/min/1.73 m\^2
• Total bilirubin outside the normal range (unless congenital hyperbilirubinemia such as Gilbert syndrome has been confirmed).
• Positive for at least 1 of the following autoantibodies at Screening: anti- double stranded DNA or anti-Smith
• Systemic Lupus Erythematosus Disease Activity Index-2000 score ≥ 8 AND at least 1 British Isles Lupus Assessment Group (BILAG)-2004 Class A (severe manifestation) organ scores
• Inadequate response to glucocorticoids and to at least 2 of the following treatments, used for at least 3 months each: cyclophosphamide, mycophenolic acid or its derivatives, belimumab, azathioprine, anifrolumab, methotrexate, rituximab, or obinutuzumab
• Subjects with neuropsychiatric SLE.
• Drug-induced SLE.
• Positive for at least 1 of the following autoantibodies at Screening: anti- double stranded DNA or anti-Smith
• Confirmed LN diagnosis by kidney biopsy during screening or within the previous 6 months, with severe active phase of the disease.
• Progressing despite maintenance on maximally tolerated doses of renin- angiotensin system (RAS) blocking agents, unless allergic to or intolerant of ACE inhibitors and ARBs

Sponsors & Collaborators

• Miltenyi Biomedicine GmbH: lead

MeSH Terms

Conditions

Lupus Nephritis; Lupus Erythematosus, Systemic; Scleroderma, Systemic; Scleroderma, Diffuse; Autoimmune Diseases; Immune System Diseases

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Esther Eromosele, MD

  Miltenyi Biomedicine

  STUDY DIRECTOR

Central Study Contacts

Sadie Swift

CONTACT

617-218-0044; clinicaltrials@miltenyi.com

Ron Gomez

CONTACT

617-218-0044; clinicaltrials@miltenyi.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2024
• First Posted: November 27, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 27, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share