Efficacy and Safety of Tocotrienols in CADASIL

NCT04658823 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: T3-CAD-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

CADASIL is a paradigmatic cerebral small vessel disease responsible for white-matter lesions, accumulation of lacunes, microbleeds and cerebral atrophy. The disease is responsible for stroke and cognitive decline associated with motor disability. The number of incident lacunes, and amount of cerebral atrophy were recently found to have a strong relationship to cognitive decline and disability progression over 3 years in a large sample of patients. Palm tocotrienols has previously shown evidence of therapeutic effect in attenuating the progression of WMH related to sporadic cerebral small vessel disease in a randomized controlled clinical trial. We hypothesize that palm tocotrienols complex (HOV-12020) can reduce the clinical progression in CADASIL.

Conditions

Cadasil

Keywords

CADASIL; Tocotrienols; Vitamin E; Vascular; Stroke; Dementia; Cerebral Small Vessel Disease; Cognitive disorder; Neurovascular disease; Hereditary multi-infarct; Cerebrovascular disease

Outcome Measures

Primary Outcomes (1)

• Incidence of manifestations related to clinical worsening

  Occurrence one failure event within 24 months after Baseline. A failure event is considered when at least one of the following manifestations is detected during the study period: * incident stroke * increase of disability corresponding to an increase in the mRS score of at least 1 point to result in a score of 2 or greater * cognitive decline corresponding to a reduction of at least 4 points of the VADAS-Cog score

  24 months

Secondary Outcomes (1)

• Incidence of adverse events

  24 months

Other Outcomes (7)

• Change of cognitive performance on CDR

  24 months

• Change of cognitive performances on MDRS

  24 months

• Change of cognitive performances on sub-subscale of MDRS

  24 months

Study Arms (2)

HOV-12020

EXPERIMENTAL

Palm tocotrienols complex Oral softgel capsule (containing 285mg mixed tocotrienols and tocopherol)

Drug: HOV-12020 (Palm tocotrienols complex)

PLACEBO

PLACEBO COMPARATOR

Placebo Oral Softgel capsule (each capsule containing vitamin E stripped soybean oil)

Drug: Placebo

Interventions

HOV-12020 (Palm tocotrienols complex) DRUG

Oral Softgel capsule containing mixed tocotrienols and tocopherol with enhanced absorption delivery system; 1 capsule twice daily

Also known as: HOV-12020, Palm Vitamin E, Tocotrienols, Tocovid Suprabio

HOV-12020

Placebo DRUG

Oral Softgel capsule containing soybean oil; 1 capsule twice daily

PLACEBO

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female
• Participants aged 45 to 75 years inclusive, at the time of signing of informed consent
• Confirmed Diagnosis of CADASIL, defined by either:
• A Typical mutation in the NOTCH3 gene responsible for an odd number of cystein residue OR
• A positive skin biopsy showing typical granular osmiophilic material (GOM) in the vascular wall of small vessels with electron microscopy
• Presence of at least one prevalent lacune on the MRI identified on 3DT1 or FLAIR images.
• Presence of Confluent white matter hyperintensities (WMH) on T2-weighted or FLAIR MR images (Fazekas grade 2-3).
• MMSE score ≥15
• mRS at 0 - 3
• A woman of child bearing potential (WOCBP) is eligible to participate if she is not pregnant, not breastfeeding, and agrees to follow contraceptive guidance (as described in Appendix 5) provided by the study clinician during the treatment period and for 28 days after the last dose of the study treatment.
• Capable of giving signed informed consent and have a patient representative willing to co-sign informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

You may not qualify if:

• Clinical stroke with persisting neurological deficit within 6 months prior to Screening.
• Any other neurodegenerative disorder, such as Parkinson's disease, Alzheimer's disease, or Huntington's disease.
• Current significant hematological, cardiac, pulmonary, metabolic, neurologic or psychiatric disorders, uncontrolled seizures, untreated hypertension, disorders increasing risk of bleeding (Hemophilia), or any other significant active medical condition which in the Investigator's opinion would impact participation in this study.
• History of myocardial infarction within 3 months prior to Screening, or current active angina pectoris, or symptomatic heart failure.
• History of cancer, within the past 5 years. Patients with basal cell carcinoma, squamous cell carcinoma, and Stage 1 prostate cancer can be included in the study.
• History of attempted suicide within 6 months prior to Screening or a positive response to items 4 or 5 of Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening and Baseline.
• History of drug or alcohol abuse or dependence.
• Contra-indications to MRI: presence of a pacemaker, severe claustrophobia, cochlear implants, ferromagnetic devices or clips, intracranial vascular clips, insulin pumps, metallic implants.
• Pregnancy or breastfeeding women.
• History of human immunodeficiency virus (HIV), hepatitis B or C.
• History of allergy or severe intolerance to Vitamin E (tocopherols / tocotrienols).
• Presence at Screening of alanine aminotransferase (ALT), aspartate aminotransferase (AST), amylase, or lipase 2x above the upper limit of normal (ULN) of laboratory reference range, total bilirubin 1.5x ULN, any other clinically significant laboratory abnormality.
• Presence at Screening of Creatinine clearance \<60 (estimated by Cockcroft-Gault equation).
• Cognitive enhancers such as donepezil, are allowed only if stable dosage within 3 months prior to Screening.
• Use of tocotrienol supplementation within 3 months prior to Screening or any current use of Vitamin E other than study drug (all other vitamin supplements are allowed, if stable dosage within 3 months prior to screening).

Sponsors & Collaborators

• Hovid Berhad: lead

Study Sites (1)

Hôpital Lariboisière APHP

Paris, 75010, France

Location

MeSH Terms

Conditions

CADASIL; Stroke; Dementia; Cerebral Small Vessel Diseases; Cognitive Dysfunction; Cerebrovascular Disorders

Interventions

Tocotrienols

Condition Hierarchy (Ancestors)

Cerebral Infarction; Brain Infarction; Brain Ischemia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia, Vascular; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

Vitamin E; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Pr Hugues Chabriat

  Hôpital Lariboisière APHP

  PRINCIPAL INVESTIGATOR

• David Ho

  Hovid Berhad

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2020
• First Posted: December 9, 2020
• Study Start: December 21, 2020
• Primary Completion: February 28, 2024
• Study Completion: October 31, 2024
• Last Updated: February 2, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)