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.

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.

Double blinded