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

Niemann-Pick Disease, Type C Clinical Trial

— RAINBOW  

Official title:

Randomized, Double Blind, Placebo Controlled, Multicenter, 12 Weeks Phase 2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral AZ-3102 in Patients With GM2 Gangliosidosis or Niemann-Pick Type C Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05758922
• Other study ID #: AZA-001-5A2-01
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 24, 2023
• Est. completion date: December 2024

Study information

• Verified date: February 2024
• Source: Azafaros A.G.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. If approved by the country health authorities, a double-blind extension period will be proposed to the patients who complete the 12-week study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 13
• Est. completion date: December 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 20 Years

Eligibility

Inclusion Criteria:

• Male and female patients aged between 12-20 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 enantiomers of 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.

Related Conditions & MeSH terms

• Gangliosidoses
• Gangliosidoses, GM2
• GM2 Gangliosidosis
• Niemann-Pick Disease, Type C
• Niemann-Pick Diseases
• Pick Disease of the Brain
• Tay-Sachs Disease

Intervention

Drug:
• AZ-3102 (Dose 1)
Pharmaceutical form: capsule Route of administration: oral
• Placebo
Pharmaceutical form: capsule Route of administration: oral
• AZ-3102 (Dose 2)
Pharmaceutical form: capsule Route of administration: oral

Locations

Country	Name	City	State
Brazil	Hospital Pequeno Principe	Curitiba
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre
Brazil	Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira	Rio De Janeiro

Sponsors (1)

Lead Sponsor	Collaborator
Azafaros A.G.

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety/tolerability: Incidence and severity of treatment emergent adverse events		Through study completion, up to Week 12
Primary	Assessment of pharmacokinetic (PK) parameters in plasma: Cmax		Through study completion, up to Week 12
Primary	Assessment of PK parameters in plasma: Tmax		Through study completion, up to Week 12
Primary	Assessment of PK parameters in plasma: AUC0-24h		Concentration versus time curve calculated from time 0 to 24 hours (AUC0-24h)