US Zamto-cel Autoimmune Diseases

November 26, 2024 updated by: Miltenyi Biomedicine GmbH

A Phase I Multicohort Trial of Zamtocabtagene Autoleucel (Zamto-Cel) in Subjects with Severe Refractory Autoimmune Diseases

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase 1, multicohort, dose-finding study evaluating autologous T cells engineered to target dual CD19 and CD20 antigens in subjects with refractory autoimmune diseases following standard therapy. The investigational product, Zamto-cel, is a chimeric antigen receptor T-cell (CAR-T) therapy genetically engineered to enable subjects' T cells to express CARs on their surfaces.

Eligible subjects will undergo leukapheresis for the collection of cells required for manufacturing. Prior to infusion of the fresh CAR-T product, subjects will receive a lymphodepleting regimen consisting of cyclophosphamide and fludarabine. The CAR-T cell infusion will be administered intravenously at a dose of 2.5 x 10^6 or 1.0 x 10^6 CAR+ cells/kg body weight, based on the dose level assigned to the cohort.

The study will initially enroll 3 subjects per cohort in a staggered manner to evaluate safety. Upon confirmation of safety, the study will proceed to cohort-specific recommended Phase 2 dose (RP2D) and dose expansion phases. Subjects will be monitored for up to 1 year to assess safety, preliminary efficacy, and health-related quality of life (HRQoL). Additional long-term follow-up will be conducted under a separate long-term follow-up protocol.

Study Type

Interventional

Enrollment (Estimated)

48

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

General Key Inclusion/Exclusion Criteria Across All Cohorts

Inclusion Criteria:

•Confirmed diagnosis of autoimmune disease (SLE-Non-renal, SLE-LN, SSc/ dcSSc)

Exclusion Criteria:

  • 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).

Systemic Lupus Erythematosus-Non-renal Key Inclusion/Exclusion Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Subjects with neuropsychiatric SLE.
  • Drug-induced SLE.

Systemic Lupus Erythematosus - Lupus Nephritis Key Inclusion/Exclusion Criteria

Inclusion Criteria:

  • 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
  • Inadequate response to glucocorticoids and hydroxychloroquine and at least 1 of the following treatments, used for at least 3 months each: cyclophosphamide, mycophenolic acid derivatives, belimumab, azathioprine, methotrexate, rituximab, obinutuzumab, calcineurin inhibitor (cyclosporin, tacrolimus or voclosporin)

Exclusion Criteria:

•Evidence of Rapidly progressive glomerulonephritis (defined as a doubling of serum creatinine within 3 months prior to enrollment) or as determined by the study investigator.

Systemic Sclerosis/Diffuse Cutaneous Systemic Sclerosis Cohort Key Inclusion/ Exclusion Criteria

Inclusion Criteria:

  • Active disease defined as:

  • Modified Rodnan skin score (mRSS) ≥ 16 units, in the prior 6 months, with 1 or more of the following:

    • Increase in mRSS by ≥ 3 units or 10%
    • Involvement of 1 new body area with increase in mRSS by ≥ 2 units
    • Involvement of 2 new body areas with increase by ≥ 1 mRSS unit OR

  • Progressive interstitial lung disease (ILD) defined as:

    - Worsening of respiratory symptoms and an increased extent of fibrosis evaluated by high-resolution computed tomography

  • Lack of response to standard therapy (e.g., failure of ≥ 2 immunosuppressive therapies)

Exclusion Criteria:

  • "Active" gastric antral vascular ectasia, as evidenced by bleeding (ie, on esophagogastroduodenoscopy) in the past 6 months or as per Investigator's assessment.
  • History of SSc renal crisis within 1 year prior to Screening; presence of kidney impairment due to conditions other than SSc

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Level 1
Drug: Cyclophosphamide
Lymphodepleting chemotherapy
Drug: Fludarabine
Lymphodepleting chemotherapy
Biological: zamtocabtagene autoleucel
chimeric antigen receptor T-cell (CAR-T) therapy
Experimental: Dose Level 2
Drug: Cyclophosphamide
Lymphodepleting chemotherapy
Drug: Fludarabine
Lymphodepleting chemotherapy
Biological: zamtocabtagene autoleucel
chimeric antigen receptor T-cell (CAR-T) therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The incidence and severity of adverse events (AEs), adverse events of special interest (AESIs), and serious adverse events (SAEs)
Time Frame: From enrollment through study completion 12 months post zamto-cel infusion
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)
Time Frame: From enrollment through Day 28 post zamto-cel infusion
From enrollment through Day 28 post zamto-cel infusion

Secondary Outcome Measures

Outcome Measure
Time Frame
The incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)
Time Frame: From enrollment through study completion 12 months post zamto-cel infusion
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
Time Frame: From enrollment through study completion 12 months post zamto-cel infusion
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
Time Frame: From enrollment through study completion 12 months post zamto-cel infusion
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
Time Frame: From enrollment through study completion 12 months post zamto-cel infusion
From enrollment through study completion 12 months post zamto-cel infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Miltenyi Biomedicine GmbH

Investigators

  • Study Director: Esther Eromosele, MD, Miltenyi Biomedicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2025

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

November 26, 2024

First Submitted That Met QC Criteria

November 26, 2024

First Posted (Estimated)

November 27, 2024

Study Record Updates

Last Update Posted (Estimated)

November 27, 2024

Last Update Submitted That Met QC Criteria

November 26, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M-2024-423

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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