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 (RAINBOW)

• ClinicalTrials.gov Identifier: NCT05758922
• Recruitment Status: Recruiting
• First Posted: March 8, 2023
• Last Update Posted: May 23, 2023
• Sponsor: Azafaros A.G.
• Information provided by (Responsible Party): Azafaros A.G.

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
GM2 Gangliosidosis; Niemann-Pick Disease, Type C	Drug: AZ-3102 (Dose 1); Drug: Placebo; Drug: AZ-3102 (Dose 2)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: April 24, 2023
• Estimated Primary Completion Date: October 2023
• Estimated Study Completion Date: October 2023

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Participant will receive placebo once daily during the course of the study (12 weeks).	Drug: Placebo; Pharmaceutical form: capsule Route of administration: oral
Experimental: AZ-3102 (Dose 1); Participant will receive AZ-3102 (Dose 1) once daily during the course of the study (12 weeks) and the study extension (if applicable).	Drug: AZ-3102 (Dose 1); Pharmaceutical form: capsule Route of administration: oral
Experimental: AZ-3102 (Dose 2); Participant will receive AZ-3102 (Dose 2) once daily during the course of the study (12 weeks) and the study extension (if applicable).	Drug: AZ-3102 (Dose 2); Pharmaceutical form: capsule Route of administration: oral

Outcome Measures

Primary Outcome Measures :

1. Safety/tolerability: Incidence and severity of treatment emergent adverse events [ Time Frame: Through study completion, up to Week 12 ]
2. Assessment of pharmacokinetic (PK) parameters in plasma: Cmax [ Time Frame: Through study completion, up to Week 12 ]
3. Assessment of PK parameters in plasma: Tmax [ Time Frame: Through study completion, up to Week 12 ]
4. Assessment of PK parameters in plasma: AUC0-24h [ Time Frame: Concentration versus time curve calculated from time 0 to 24 hours (AUC0-24h) ]

Eligibility Criteria

• Ages Eligible for Study: 12 Years to 20 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Christian Freitag, MD; +41 78 259 80 80; chris.freitag@azafaros.com

Contact: Cécile Paquet-Luzy; cecile.paquet-luzy@azafaros.com

Locations

United States, Minnesota

Mayo Clinic Rochester; Recruiting

Rochester, Minnesota, United States, 55905

Contact: Marc Patterson, MD

Brazil

Hospital Pequeno Principe; Recruiting

Curitiba, Brazil

Contact: Daniel Almeida do Valle, MD +55 41 3310-1356 pesquisa-clinica@hpp.org.br

Hospital de Clinicas de Porto Alegre; Recruiting

Porto Alegre, Brazil

Contact: Roberto Giugliani, MD +55 51 3359-6338 rgiugliani@hcpa.edu.br

Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira; Recruiting

Rio De Janeiro, Brazil

Contact: Dafne Dain Gandelman Horovitz, MD +55 21 2554-1709 dafne.horovitz@fiocruz.br

Sponsors and Collaborators

Azafaros A.G.

More Information

• Responsible Party: Azafaros A.G.
• ClinicalTrials.gov Identifier: NCT05758922
• Other Study ID Numbers: AZA-001-5A2-01
• First Posted: March 8, 2023
• Last Update Posted: May 23, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Gangliosidoses, GM2; Pick Disease of the Brain; Gangliosidoses; Niemann-Pick Diseases; Niemann-Pick Disease, Type A; Niemann-Pick Disease, Type C; Tay-Sachs Disease; Frontotemporal Dementia; Frontotemporal Lobar Degeneration; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Metabolic Diseases; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases