phase 2 study evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of oral az-3102 in patients with gm2 gangliosidosis or niemann-pick type c disease

Conditions: GM2 Gangliosidosis; Niemann-Pick Disease, Type C

Summary: this phase 2 is a randomized, double-blind, placebo controlled, 12 weeks study with daily oral administration of az-3102 aiming to evaluate the safety and pharmacokinetic (pk) profile in gm2 gangliosidosis and niemann-pick type c disease (np-c) patients. after approval by the country health authorities, a double-blind extension period was proposed to the patients who complete the 12-week study.


Eligibility criteria:
inclusion criteria: * male and female patients aged above 12 years old at informed consent signature. * gm2 patients : genetically and biochemically confirmed diagnosis of tay-sachs or sandhoff disease. * np-c patients : genetically confirmed diagnosis of np-c. * np-c patients : miglustat-naïve patients unwilling or unable to take miglustat, or, patients who have discontinued miglustat because of confirmed safety/tolerability issues. miglustat must have been discontinued at least 1 month prior to baseline visit. * total sara score ≥ 1 at baseline. * a male participant with a female partner of childbearing potential is eligible if he agrees to follow the contraceptive guidance. * if a female participant is a wocbp and is having a male partner, she must agree to follow the contraceptive guidance. * willing and able to complete protocol assessments. * parent and/or legal guardian is able to read, understand, and sign the informed consent. where appropriate, assent will also be sought for patients who have not reached the age of majority or who are not able to sign the consent form. exclusion criteria: * any abnormal conditions at baseline visit which, in the opinion of the pi; could interfere with study assessments (e.g., severe infection). * history of medical conditions other than gm2 gangliosidosis/np-c that, in the opinion of the pi; would confound scientific rigor or interpretation of results. * presence of another inherited neurologic disease. * the dose of anti-epileptic treatment(s) was not stable and/or a new anti-epileptic treatment (drug or procedure) was prescribed during the last month before baseline. * total bilirubin \>2 x uln (isolated bilirubin \>2 x uln is acceptable if bilirubin is fractionated and direct bilirubin is \<35%). * platelet count \< 100 x 10\^9/l. * presence of moderate or severe renal impairment. * prior participation in a clinical study with an investigational drug within 3 months prior to baseline. * patient with a positive serum pregnancy test (tested only for women of childbearing potential) at baseline. * breast feeding ongoing at baseline or planned during the study. * ecg with an average of triplicate qtcf interval \> 440 msec. * received treatment with n-acetyl-leucine, gene therapy, stem cell transplantation, or with any other azasugars (iminosugars) compound with similar mechanism of action within 3 months before baseline (except for miglustat for which it is 1 month). * any known allergy to azasugars or any excipients. * evidence of suicidal ideation with intent (type 4-5) on the columbia suicide severity rating scale (c-ssrs) at screening. only in patients judged by the pi cognitively capable to understand the concept of suicide.