Abstract Details

A-T is a devastating recessive disorder characterized by progressive neurological deterioration, immunodeficiency and/or malignancy. 

The phase 3 ATTeST study assessed the efficacy and safety of monthly infusions of intra-erythrocyte dexamethasone phosphate (EDS) in patients with A-T.

175 A-T patients (mean age 10.1+ 4.17 years) were randomized  to EDS dose ranges of ~5-10 mg, or ~14-22 mg, or placebo every 30 days. The primary efficacy outcome was the modified international cooperative ataxia rating scale (mICARS and RmICARS). The trial was registered with ClinicalTrials.gov number: NCT02770807 and is completed, the study sponsor is EryDel, SpA.

Between March 2017 and March 2020, 175 patients were enrolled and 164 were randomized; 132 (80.5 %) completed the 24 weeks of the primary efficacy period. The Full Analysis Set (FAS, N=164) showed favourable primary outcomes in the treated groups compared to placebo, but did not reach statistical significance.

The per-protocol (PP) analysis (N=107) showed slower rate of neurologic deterioration for both doses compared to placebo (mICARS p=0.004 low dose and 0.019 high dose; RmICARS p=0.003 and 0.036 high dose).  The a priori age 6–9-year olds’ ITT analysis (N=89) showed a statistically significant favourable outcome for high dose vs placebo (mICARS p=0.019 and RmICARS p=0.028).Treatment-emergent adverse events occurred in  43 (73%) 47 (82%),and 43 (73%) patients in  the low dose, high dose, and placebo group, respectively, and serious adverse events in 6 (10%), 7 (12%), and 7 (12%) patients respectively. There were no clinically important known adverse effects of corticosteroids and no deaths.

The 6 months safety analysis showed that EDS was well tolerated and did not identify any alarming safety signals that might be expected with chronic steroid use. The efficacy analysis showed that progression of neurological motor decline was significantly blocked by the high dose EDS treatment, more clearly evident in the younger children.