Theranexus and the Beyond Batten Disease Foundation have announced receipt of approval from the Food and Drug Administration (FDA) for the design and primary and secondary endpoints of the pivotal Phase III trial for Batten disease CLN3, at a meeting with the Division of Rare Diseases and Medical Genetics (DRDMG) held in mid-April. Theranexus and BBDF worked with the FDA's DRDMG to define the following criteria for the protocol of the Phase III multicenter trial for evaluating Batten-1 in patients with juvenile Batten disease (CLN3): The trial will be a randomized, double-blind study conducted versus placebo in 2 parallel groups to assess the efficacy of Batten-1 at a dose of 15 mg/kg and up to 600 mg/day for a 2-year treatment period, The target population will be a pediatric cohort involving approximately 60 patients aged 4 to 16 years, with randomization stratified into 3 age groups of 4 to 8 years, 9 to 12 years and 13 to 16 years to achieve suitable representation for all age groups assessed, The primary endpoint will be visual acuity, measured using either the quantitative LogMAR[1] scale, or a qualitative scale in the most impaired patients for whom quantitative assessment is not possible, The secondary endpoints will include cognitive function, assessed by the Verbal Comprehension Index from the Wechsler Intelligence Scale for Children according to age, motor function assessed by a selection of motor items from the Unified Batten Disease Rating Scale (UBDRS), and visual function, assessed by OCT scan, An assessment of functional ability in everyday activities and a Quality-of-Life measurement will also be performed. An additional open-label cohort of 9 patients' representative of the different age groups of the target population will be enrolled in parallel.

This will allow to enrich the statistical analysis plan, in particular in comparison with natural history data, for the primary and secondary endpoints on trial completion, and produce interim results every 6 months, including measurements of biomarkers (notably glycosphingolipids given their toxic accumulation resulting in neuronal death) and efficacy data on the same criteria as the main 60-patient cohort. Patient enrollment should begin in the end of 2023. The trial will run in parallel in several centers throughout the United States and Europe.

Provided positive results are registered, the FDA confirms that a sole Phase III trial as defined above would secure approval of the Batten-1 candidate in Batten disease. The company's goal is to use the results of this trial to win product approval in both the United States and Europe. As a reminder, the Phase III trial follows on from Phase I/II whose initial results showed good safety and tolerability of miglustat in a population of CLN3 patients over 17 years of age, and a pharmacokinetic profile in line with expectations.