Ph1 T-Regulatory Cells in Amyotrophic Lateral Sclerosis

ALS (Amyotrophic Lateral Sclerosis)

ALS, T-Regulatory Cells

Open-label pilot study to determine the safety and tolerability of autologous CD4+ CD25+ regulatory T cells infusions with concomitant subcutaneous IL-2 injections taken 3 times per week in 3 participants with ALS.

This is Pilot Study will consist of 3 people diagnosed with amyotrophic lateral sclerosis (ALS), who will undergo 4 infusions of autologous expanded Tregs and concomitant subcutaneous injections of Interleukin-2 \[IL-2\] (2 x 105 IU/m2) 3 times weekly, for 52 weeks or unless the interim analysis confirms or negates the investigational product (IP = Tregs) use. During the enrollment period up to three research participants will be recruited from patients in our ALS Clinic for screening, baseline measures and leukapheresis. The Treg cell manufacturing will be performed in a current Good Manufacturing Practice (cGMP) laboratory. The first subject will receive infusions of their expanded Tregs (1x106 /kg) with concomitant subcutaneous IL-2 injections (2 x 105 IU/m2) 25 days (+/- 2 days) post leukapheresis. The 2nd subject will begin after the first subject has completed the first 4 weeks and has experienced no untoward effects during this period. Once subjects #1 and #2 have completed the first 4 weeks and no toxic events have occurred they will therefore be considered safely past the first milestone and subject #3 will begin infusions. Research Participants #1, 2 and 3 will repeat the leukapheresis (under a separate protocol) and undergo Treg infusions at the modified schedule of every 4 weeks, with concomitant subcutaneous injections of IL-2 (2 x 105 IU/m2) 3 times weekly. The subjects will be called on Day 7, and 21. Office visits will be completed on the day after infusions and every two weeks while the subjects are undergoing Treg infusions for clinical evaluation, scoring, and blood draws. The subjects will then be seen during office visits once per month for one year total from their initial baseline visit for clinical evaluation, scoring, and blood draws Monthly interim analyses will monitor the subjects using validated ALS scales such as the ALS Functional Rating Scale-Revised (ALSFRS-R) and Appel ALS Grading Scale (AALS), which incorporates muscle strength and dysfunction, activities of daily living and pulmonary function. The analyses will also include interim medical history and physical exam, an electrocardiogram (ECG) when indicated, pulmonary function tests (PFTs) such as Forced vital capacity (FVC) and Maximum Inspiratory Pressure (MIP or MIPS), safety labs (such as a complete blood count (CBC), chemistry, liver function, thyroid tests-T4 and TSH) as well as more technical research labs such as T Regulatory Cell and related markers (Th1 and Th17 counts, FoxP3 RNA expression), and Treg Suppression Assays. A prothrombin time (PT) and partial thromboplastin time (PTT) will be performed only if the subject has an abnormal coagulation result at baseline or if the subject is on anti-coagulation therapy. Adverse Events (AEs) and Serious Adverse Events (SAEs) will be monitoring from the time of consent until end of study or AE/SAE resolution.

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United States