In Amyotrophic Lateral Sclerosis (ALS), the reduction of regulatory T-lymphocyte (Treg) numbers and suppressive function correlates with rapid disease progression. The investigator completed a phase 1 study of infusions of expanded autologous Tregs in combination with subcutaneous IL-2 injections in ALS patients, which showed enhancement of Treg numbers and suppressive function in vivo. The enhanced Treg suppressive function correlated strongly with slowing and stabilization of disease progression. Drugs that enhance endogenous Treg numbers and suppressive function may also stabilize disease in ALS. This phase 1 study aims to determine whether the combination therapy of subcutaneous IL-2 and abatacept (Orencia®) is safe and well-tolerated in 6 patients with ALS, and whether the therapy enhances Treg numbers and suppressive function in vivo.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
5
Abatacept (Orencia®) and recombinant human IL-2 (aldesleukin). Patients will receive a fixed dose of subcutaneous abatacept (125 mg/mL) at day 1. Two weeks later (day 15), patients will receive the second dose of subcutaneous abatacept (125 mg/mL). In addition, patients will receive subcutaneous IL-2 (1x106units /day) for 5 days (days 15-19). If this treatment regimen is tolerated, patients will receive 28 further similar treatment courses of abatacept and IL-2 every two weeks.
Houston Methodist Research Institute
Houston, Texas, United States
To evaluate adverse events and laboratory abnormalities to assess the safety and tolerability of abatacept followed by Interleukin 2 (IL-2) administration in ALS patients
Incidence and severity of AEs, including changes in laboratory values and vital signs. The investigator will determine whether safety and tolerability of abatacept followed by IL-2 administration are acceptable in order to proceed with the next phase. Safety and tolerability will be assessed throughout the study.
Time frame: 24 months
Change in Regulatory T cells (Tregs) numbers in the blood from baseline
The change in the number of Tregs.will be monitored The investigator hypothesizes that increasing Treg numbers and suppressive function will slow the progression of ALS, and the investigator will determine whether these markers increase in response to Abatacept/IL-2 administration.
Time frame: Baseline to Week 15
Change in Regulatory T cells (Tregs) suppressive function in the blood from baseline
The change in the suppressive activity of Tregs on responder T cell proliferation will be monitored The investigator hypothesizes that increasing Treg numbers and suppressive function will slow the progression of ALS, and the investigator will determine whether these markers increase in response to Abatacept/IL-2 administration.
Time frame: Baseline to Week 15
Changes in the level of cytokines secreted by PBMCs from baseline
The level of cytokines secreted by PBMCs throughout the course of the study The investigator hypothesizes that modulating peripheral inflammatory cytokines will slow the progression of ALS, and the investigator will determine whether these markers decrease in response to Abatacept/IL2 administration.
Time frame: Baseline to Week 15
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