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

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)

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

Study Overview

• Status: Withdrawn
• Conditions: X-Linked Adrenoleukodystrophy
• Intervention / Treatment: Drug: Sobetirome (NV1205)

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 Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Hospital Austral
  • Buenos Aires, Argentina
    • Hospital General de Niños Pedro de Elizalde
• Australia
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health
• Chile
  • Santiago, Chile
    • Hospital Clinico San Borja Arriarán
  • Santiago, Chile
    • Hospital Dr. Luis Calvo Mackenna
• Colombia
  • Bogotá, Colombia
    • Fundacion Cardioinfantil
• France
  • Paris, France
    • Hôpital Bicêtre - Paris Sud
• Russian Federation
  • Moscow, Russian Federation
    • Endocrinology Research Center
  • Moscow, Russian Federation
    • Moscow Morozov's Children Clinical Hospital
  • Saint Petersburg, Russian Federation
    • Saint Petersburg State Pediatric Medical University
• Ukraine
  • Kiev, Ukraine
    • National Children's Specialized Hospital 'OKHMATDET'
• United Kingdom
  • London, United Kingdom
    • Great Ormond Street Hospital for Children
  • Manchester, United Kingdom
    • Manchester Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Adverse events	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve concentration of NV1205 in plasma	A sparse sampling approach will be utilized to estimate a 24-hr area under the curve of NV1205 plasma concentration	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Loes score	Percent change from baseline in brain lesions assessed as Loes score will be calculated	2 years

Collaborators and Investigators

• Sponsor: NeuroVia, Inc.
• Investigators: Study Director: John Henderson, MD, NeuroVia, Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2018
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: May 5, 2017
• First Submitted That Met QC Criteria: June 21, 2017
• First Posted (Actual): June 23, 2017

Study Record Updates

• Last Update Posted (Actual): March 7, 2019
• Last Update Submitted That Met QC Criteria: March 6, 2019
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: X-ALD
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Demyelinating Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Endocrine System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Leukoencephalopathies; Adrenal Gland Diseases; Hereditary Central Nervous System Demyelinating Diseases; Peroxisomal Disorders; Adrenal Insufficiency; Adrenoleukodystrophy
• Other Study ID Numbers: NV1205-009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No