Combined Regulatory T-Lymphocyte and IL-2 Treatment Is Safe, Tolerable, and Biologically Active for 1 Year in Persons With Amyotrophic Lateral Sclerosis

(A) Treg suppressive function was assessed in each participant in the placebo and Treg/IL-2 treatment groups at screening and week 24 (4 weeks after the last infusion of the RCT). (B) Treg numbers were assessed in each participant in the placebo and Treg/IL-2 treatment groups at screening and week 24 (4 weeks after the last infusion of the RCT). Data were depicted as visit-specific estimates ±standard error and were compared for progression of continuous end points using a shared-baseline, linear mixed model. A p < 0.05 was considered significant. IL = interleukin; RCT = randomized controlled trial; Treg = regulatory T-lymphocyte.

(A) Four participants were randomized to the placebo group and received infusions every 4 weeks as depicted by the vertical dotted lines. Infusions #1–6 were placebo infusions in the RCT, and #7–12 were Treg infusions in the OLE. (B) Three participants were randomized to the active group (Treg/IL-2 treatment) and received infusions every 4 weeks. Infusions #1–6 were Treg infusions in the RCT, and #7–12 were Treg infusions in the OLE. Disease progression was documented in each participant by the ALSFRS-R over the duration of the 54-week study including the screening period. Placebo or IL-2 subcutaneous injections were administered beginning 2–4 weeks before the first infusion at week 0 for the RCT and 2 weeks before the 7th infusion at week 26 for the OLE. (C) Two participants were directly enrolled into the OLE and received Treg infusions every 4 weeks as depicted by the vertical dotted lines. Disease progression was documented in each participant by the ALSFRS-R over the duration of the 28-week study including the screening period. IL-2 subcutaneous injections were administered beginning 4 weeks before the first infusion at week 0. ALSFRS-R = ALS Functional Rating Scale–Revised; IL = interleukin; OLE = open-label extension; RCT = randomized controlled trial; Treg = regulatory T-lymphocyte.

(A) Treg suppressive function was assessed in each participant at screening, 4 weeks after the second infusion of a 1× dose of Tregs (week 34), 4 weeks after the second infusion of a 2× dose (week 42), and 4 weeks after the second infusion of a 3× dose (week 50). (B) Treg numbers were assessed in each participant at screening, 4 weeks after the second infusion of a 1× dose of Tregs (week 34), 4 weeks after the second infusion of a 2× dose (week 42), and 4 weeks after the second infusion of the 3× dose (week 50). Data were depicted as visit-specific estimates ±standard error and were compared for progression of continuous end points using a shared-baseline, linear mixed model. A p < 0.05 was considered significant. Treg = regulatory T-lymphocyte.

Disease progression was documented in each participant by the ALSFRS-R over the duration of the 24-week OLE. The timing of the Treg infusions was depicted by the vertical dotted lines with the corresponding Treg dosages. The baseline ALSFRS-R value for the OLE was taken at week 26 for the 6 participants who went through the RCT and week 0 for the 2 participants who entered directly into the OLE. The total change in the ALSFRS-R was calculated after 24 weeks. Six of the 8 participants showed intermediate to no progression of the ALSFRS-R (average of −2.7 points). Two of the 8 participants showed rapid progression (average of −10.5 points). ALSFRS-R = ALS Functional Rating Scale–Revised; Treg = regulatory T-lymphocyte.