NPC is a rare, autosomal recessive lysosomal storage disorder. The IB1001-301 clinical trial was a Phase III, double-blind, randomized, placebo-controlled cross-over trial comparing NALL with placebo for treating neurological signs and symptoms in NPC.

SARA is a validated eight-item clinical rating scale that incorporates assessments of gait, stance, sitting, speech disturbance, finger-chase, nose-to-finger, fast-alternating-hand movements, and heel-along-shin slide.

To evaluate the efficacy of N-acetyl-L-leucine (NALL) compared to placebo within each of the eight items of the Scale for the Assessment and Rating of Ataxia (SARA). 

Patients received treatment with orally administered NALL 2-3 times per day as weight-based dosing. The primary end point was the total score on the SARA (range, 0 to 40, with lower scores indicating better neurologic status).

60 patients aged 5 to 67 years were enrolled in the trial and underwent randomization.

The mean change from baseline in the total score on the SARA was −1.97±2.43 points after 12 weeks of receiving NALL and −0.60±2.39 points after 12 weeks of receiving placebo (least-squares mean difference, −1.28 points; 95% confidence interval [CI], −1.91 to −0.65; P<0.001). 

On all 8 SARA domains, there was a statistically significant improvement versus baseline when patients received NALL, and greater improvement on all domains while patients were treated with NALL versus placebo. The treatment effect of NALL within each of the eight items was consistent with the overall SARA scores favoring NALL treatment.

NALL was well-tolerated, and no treatment-related serious AEs occurred.

Analysis of the SARA subdomains demonstrated consistent improvement across each domain and the associated functional area—including ambulation, postural balance, speech, fine motor skills, and upper and lower extremity function. There was a consistent improvement with NALL versus placebo demonstrating the positive effects of NALL across a broad range of neurological functions.