A Phase I, Open-Label, Dose Escalation Trial Exploring the Safety and Tolerability of Autologous Polyclonal Regulatory T Cell Therapy in Adults With Active Cutaneous Lupus (ALE08)
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Lupus Erythematosus, Cutaneous
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 1
- Locations
- 1
- Primary Endpoint
- Number of Significant Adverse Events (AEs) Through Week 48
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
Brief Summary
The primary purpose of this Phase 1 study is to evaluate the safety, tolerability, and effect of 3 different doses of Treg therapy in adults with skin (cutaneous) involvement of their lupus. Targeting cutaneous disease offers the ability to control background therapy, readily detect clinical effects, and perform research analyses not only in blood but also skin. Safety, disease activity, and mechanism of Tregs will be evaluated. The intent is to support dose selection for a future larger efficacy trial in lupus.
Detailed Description
The investigational therapy in this trial, regulatory T cells (Tregs), is evaluating an alternative to traditional immunosuppressive therapies for the treatment of systemic lupus erythematosus (SLE, lupus). Too frequently, aggressive therapies are inadequate in the control of the disease and have potent side effects and complications. The collection and expansion of one's own T cells harnesses a naturally occurring regulatory mechanism to restore self-tolerance in people with lupus. Tregs are a specialized subset of T cells that function to control the immune response. Studies have shown that in active lupus, the numbers and function of Treg cells are significantly decreased, which contributes to an overactive immune system and an increase in disease activity. The hope is that these naturally occurring Treg cells can be used for the treatment of autoimmune diseases, including lupus.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Ability to provide informed consent.
- •Diagnosis of SLE by American College of Rheumatology (ACR) criteria or biopsy proven primary cutaneous lupus.
- •Presence of ≥ 2 active cutaneous lupus lesions based on (1) visual morphology and (2) at least a grade 2 erythema on CLASI activity score. Histopathologic confirmation is required unless the active lesions are of the same morphology to previously histologically proven cutaneous lupus lesions.
- •The cutaneous lupus lesions must include any of the following subtypes:
- •Acute cutaneous lupus including maculopapular lupus rash and photosensitive lupus rash,
- •Subacute cutaneous lupus,
- •Chronic cutaneous lupus including discoid lupus and hypertrophic (verrucous) lupus,
- •Lupus timidus
- •Positive test for Epstein-Barr virus (EBV) antibody.
- •Adequate venous access to support draw of 400 mL whole blood and infusion of investigational therapy.
Exclusion Criteria
- •New onset of cutaneous lupus which has not been treated with broad spectrum sunscreen (UVA and UVB) in combination with either antimalarials or another systemic medication for at least 3 months.
- •Prednisone dose \> 15mg/day within the 30 days prior to screening.
- •Addition of a new medication, or change in the dose of any background medication, used to treat any aspect of SLE. Specifically:
- •addition or change in systemic glucocorticoids, antimalarials, methotrexate, mycophenolate mofetil, mycophenolic acid, azathioprine, cyclosporine, tacrolimus, thalidomide, lenalidomide, dapsone, acitretin, or isotretinoin within 90 days prior to screening
- •treatment with cyclophosphamide within 90 days prior to screening.
- •Doses of background medications at Screening visit:
- •hydroxychloroquine \> 400 mg/day,
- •chloroquine \> 250 mg/day,
- •quinacrine \>100 mg/day,
- •methotrexate \> 25 mg/week,
Outcomes
Primary Outcomes
Number of Significant Adverse Events (AEs) Through Week 48
Time Frame: From time of signed informed consent to Week 48
A significant adverse event is any related National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 4.0 Grade 3 or higher AE or any related serious adverse event. Related is defined as being possibly, probably, or definitely related to the ex vivo expanded autologous PolyTregs, as determined by the safety review committee.
Secondary Outcomes
- Number of Lupus Flares Through Week 152 by Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Criteria(From time of signed informed consent to Week 152)
- Number of Significant Adverse Events (AEs) Through Week 152(From time of signed informed consent to Week 152)
- Change From Baseline: Alkaline Phosphatase (ALK), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST)(Baseline (Visit 0) and Weeks 4, 12, 48, and 152)
- Change From Baseline in mg/dL: Total Bilirubin, Creatinine(Baseline (Visit 0) and Weeks 4, 12, 48, and 152)
- Change From Baseline in Physician's Global Assessment (PhGA)(Baseline (Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152)
- Number of Grade 3 or Higher Adverse Events (AEs) Through Week 152(From time of signed informed consent to Week 152)
- Number of Infection-Related Adverse Events (AEs) Through Week 152(From time of signed informed consent to Week 152)
- Number Infusion-Related Adverse Events (AEs) Within 24 Hours of Infusion(From time of infusion to 24 hours post infusion)
- Change From Baseline in Cell Counts: White Blood Cells (WBC), Total Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets(Baseline (Visit 0) and Weeks 4, 12, 48, and 152)
- Change From Baseline Red Blood Cell Count(Baseline (Visit 0) and Weeks 4, 12, 48, and 152)
- Change From Baseline in SELENA-SLEDAI Total Score(Baseline (Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152)
- Change From Baseline in Patient's Global Assessment (PGA)(Baseline (Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152)
- Change From Baseline in g/dL: Albumin, Hemoglobin(Baseline (Visit 0) and Weeks 4, 12, 48, and 152)
- Change From Baseline in Serum C3 Complement Levels(Baseline (Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152)
- Change From Baseline in Serum C4 Complement Levels(Baseline (Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152)
- Change From Baseline in mmol/L: Potassium, Sodium, Chloride(Baseline (Visit 0) and Weeks 4, 12, 48, and 152)
- Change From Baseline in mm/hr: Sedimentation Rate (ESR)(Baseline (Visit 0) and Weeks 4, 12, 48, and 152)
- Change From Baseline in Anti-dsDNA Antibody Titers(Baseline ( Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152)
- Change From Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score(Baseline (Visit 0) and Weeks 12, 24, 36, 48, 100, 126, and 152)