US Zamto-cel Autoimmune Diseases

Launched by MILTENYI BIOMEDICINE GMBH · Nov 26, 2024

Keywords

ClinConnect Summary

The US Zamto-cel Autoimmune Diseases trial is studying a new treatment called zamtocabtagene autoleucel (zamto-cel) for patients with difficult-to-treat autoimmune diseases, specifically lupus nephritis, systemic lupus erythematosus, and systemic sclerosis. This is an early-phase clinical trial that aims to determine how safe the treatment is and how well patients tolerate it after they have already tried standard therapies without success. The trial is not yet recruiting participants but will include men and women aged 65-74 who have a confirmed diagnosis of one of these autoimmune conditions.

To be eligible for the trial, participants must have certain test results showing active disease and must not have had previous gene therapy or significant infections. For instance, those with lupus must show specific autoantibodies and have not responded well to commonly used treatments like steroids or immunosuppressive drugs. If chosen to participate, individuals can expect close monitoring of their health as they receive the new treatment. It's important to note that this study will help researchers understand the potential benefits and risks of zamto-cel for these challenging conditions.

Gender

ALL

Eligibility criteria

• • 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