Safety, Pharmacokinetics and Pharmacodynamics of NV1205 in Pediatric Male Subjects With Adrenoleukodystrophy

• ClinicalTrials.gov Identifier: NCT03196765
• Recruitment Status: Withdrawn
• First Posted: June 23, 2017
• Last Update Posted: March 7, 2019
• Sponsor: NeuroVia, Inc.
• Information provided by (Responsible Party): NeuroVia, Inc.

Study Description

Brief Summary:

This is a phase I/II, open label dose escalation study of multiple dose levels of NV1205 with a long-term treatment phase.

Condition or disease	Intervention/treatment	Phase
X-Linked Adrenoleukodystrophy	Drug: Sobetirome (NV1205)	Phase 1; Phase 2

Detailed Description:

This study is to evaluate the safety, pharmacokinetics, and efficacy of NV1205 in pediatric patients diagnosed with childhood cerebral adrenoleukodystrophy (CCALD).

The study consists of:

• Screening period: within 30 days of first dose
• Main treatment period of 12 weeks (Part 1- from Screening to Week 12)
• Long Term Treatment (LTT) period (Part 2- Week 13 through Week 96)

In Part 1, subjects will have an initial 4-week treatment period at the assigned dose and, if no safety concerns are noted, subjects continue for another 8 weeks of extended safety assessment.

There will be several cohorts of subjects enrolled. After each Cohort has completed the 4-week initial safety assessment, the safety data will be reviewed by an independent Data Safety Monitoring Board (DSMB) and, subject to DSMB recommendation, Cohort 2 will be enrolled and receive the next dose level. After Cohort 2 has completed 4 weeks of treatment, the DSMB will review all available safety data (Cohorts 1 and 2) and, subject to DSMB recommendation, Cohort 3 will be enrolled and receive the next dose level. Additional Cohorts may be enrolled at the recommendation of the DSMB with an incremental dose increase.

In Part 2, subjects will continue to receive treatment in the LTT period of the study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Intervention Model: Sequential Assignment
• Intervention Model Description: Sequential dose escalation
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II, Open-Label, Dose Escalation Study of the Safety, Pharmacokinetics and Pharmacodynamics of NV1205 in Pediatric Male Subjects With Childhood Cerebral Adrenoleukodystrophy (CCALD)
• Estimated Study Start Date: August 2018
• Estimated Primary Completion Date: December 1, 2020
• Estimated Study Completion Date: December 1, 2020

Arms and Interventions

Intervention Details:

• Drug: Sobetirome (NV1205)
  Once a day oral dose of the study drug
  Other Name: NV1205

Outcome Measures

Primary Outcome Measures :

1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 2 years ]
   Adverse events

Secondary Outcome Measures :

1. Area under the curve concentration of NV1205 in plasma [ Time Frame: 12 weeks ]
   A sparse sampling approach will be utilized to estimate a 24-hr area under the curve of NV1205 plasma concentration

Other Outcome Measures:

1. Loes score [ Time Frame: 2 years ]
   Percent change from baseline in brain lesions assessed as Loes score will be calculated

Eligibility Criteria

• Ages Eligible for Study: 4 Years to 18 Years (Child, Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Males ≥4 years and <18 years of age
2. CCALD diagnosis confirmed by genetic testing
3. Loes score of >0 and ≤15
4. Patients on VLCFA lowering agents such as Lorenzo's oil must stop the medication and have high VLCFA levels before enrollment

Exclusion Criteria:

• Significant medical conditions such as heart, thyroid, or liver disease
• HSCT recipients

Contacts and Locations

Locations

Argentina

Hospital Austral

Buenos Aires, Argentina

Hospital General de ninos Pedro de Elizalde

Buenos Aires, Argentina

Australia, Victoria

Monash Health

Clayton, Victoria, Australia, 3168

Chile

Hospital Clínico San Borja Arriarán

Santiago, Chile

Hospital Dr. Luis Calvo Mackenna

Santiago, Chile

Colombia

Fundacion Cardioinfantil

Bogotá, Colombia

France

Hôpital Bicêtre - Paris Sud

Paris, France

Russian Federation

Endocrinology Research Center

Moscow, Russian Federation

Moscow Morozov's Children Clinical Hospital

Moscow, Russian Federation

Saint Petersburg State Pediatric Medical University

Saint Petersburg, Russian Federation

Ukraine

National Children's Specialized Hospital 'OKHMATDET'

Kiev, Ukraine

United Kingdom

Great Ormond Street Hospital for Children

London, United Kingdom

Manchester Children's Hospital

Manchester, United Kingdom

Sponsors and Collaborators

NeuroVia, Inc.

Investigators

• Study Director: John Henderson, MD; NeuroVia, Inc.

More Information

• Responsible Party: NeuroVia, Inc.
• ClinicalTrials.gov Identifier: NCT03196765
• Other Study ID Numbers: NV1205-009
• First Posted: June 23, 2017
• Last Update Posted: March 7, 2019
• Last Verified: May 2018

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

Keywords provided by NeuroVia, Inc.:

X-ALD

Additional relevant MeSH terms:

Adrenoleukodystrophy; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Demyelinating Diseases; Mental Retardation, X-Linked; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Peroxisomal Disorders; Metabolic Diseases; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases