Efficacy and Safety of Tocotrienols in CADASIL

Brief Title

Efficacy and Safety of Tocotrienols in CADASIL

Official Title

A Randomized Placebo-controlled Double-blind Pilot / Phase II Study to Assess the Efficacy and Safety of HOV-12020 in Patients With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL)

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.
    


Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Incidence of manifestations related to clinical worsening

Secondary Outcome

 Incidence of adverse events

Condition

Cadasil

Intervention

HOV-12020 (Palm tocotrienols complex)

Study Arms / Comparison Groups

 HOV-12020
Description:  Palm tocotrienols complex Oral softgel capsule (containing 285mg mixed tocotrienols and tocopherol)

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

50

Start Date

December 21, 2020

Completion Date

December 31, 2023

Primary Completion Date

December 31, 2023

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female

          2. Participants aged 45 to 75 years inclusive, at the time of signing of informed consent

          3. 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

          4. Presence of at least one prevalent lacune on the MRI identified on 3DT1 or FLAIR
             images.

          5. Presence of Confluent white matter hyperintensities (WMH) on T2-weighted or FLAIR MR
             images (Fazekas grade 2-3).

          6. MMSE score ≥15

          7. mRS at 0 - 3

          8. 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.

          9. 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.

        Exclusion Criteria:

          1. Clinical stroke with persisting neurological deficit within 6 months prior to
             Screening.

          2. Any other neurodegenerative disorder, such as Parkinson's disease, Alzheimer's
             disease, or Huntington's disease.

          3. 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.

          4. History of myocardial infarction within 3 months prior to Screening, or current active
             angina pectoris, or symptomatic heart failure.

          5. 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.

          6. An episode of major depression within the last 6 months prior to Screening (clinically
             stable minor depression is not exclusionary).

          7. 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.

          8. History of drug or alcohol abuse or dependence.

          9. Contra-indications to MRI: presence of a pacemaker, severe claustrophobia, cochlear
             implants, ferromagnetic devices or clips, intracranial vascular clips, insulin pumps,
             metallic implants.

         10. Pregnancy or breastfeeding women.

         11. History of human immunodeficiency virus (HIV), hepatitis B or C.

         12. History of allergy or severe intolerance to Vitamin E (tocopherols / tocotrienols).

         13. 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.

         14. Presence at Screening of Creatinine clearance <60 (estimated by Cockcroft-Gault
             equation).

         15. Cognitive enhancers such as donepezil, are allowed only if stable dosage within 3
             months prior to Screening.

         16. 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).

         17. Participation in a clinical trial with investigational product (IP) within 30 days
             prior to Screening. Patients participating in observational studies with no IP, will
             be allowed to participate in this study

         18. Indication for anti-coagulant therapy

         19. Patients with known sensitivity to polyoxyl castor oil or risk of allergy to soybean
             and peanuts.
      

Gender

All

Ages

45 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

Pr Hugues Chabriat, 33 (0)1 49952597, [email protected]

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT04658823

Organization ID

T3-CAD-01


Responsible Party

Sponsor

Study Sponsor

Hovid Berhad


Study Sponsor

Pr Hugues Chabriat, Principal Investigator, Hôpital Lariboisière APHP


Verification Date

December 2020