TEASE is a Phase 2 Multicenter, Double-Masked, Randomized, Placebo-Controlled Study to Investigate the Long Term Safety, Tolerability, Pharmacokinetics and Effects of ALK-001 on the Progression of Stargardt Disease.
Main Eligibility Criteria
- Male or female between 12 and 60 years old (inclusive), with any visual acuity. Ages outside of this range may possibly be eligible.
- Has a clinical diagnosis of typical autosomal recessive Stargardt macular dystrophy (STGD1)
- Has provided a genetic report indicating at least two ABCA4 disease-causing mutations. When only one ABCA4 disease-causing mutation is reported, sponsor’s permission will be required.
- At least one eye (called the “primary study eye”) must have at least one well-demarcated area of significantly reduced autofluorescence as imaged by fundus autofluorescence (FAF)
- Primary study eye must have clear ocular media and adequate pupillary dilation, including no allergy to dilating eyedrops, to permit good quality retinal imaging
- Healthy as judged by investigator
- Able and willing to comply with study requirements, restrictions and instructions and is likely to complete the 24-month study
- Has signed and dated the informed consent forms (or assent where appropriate) to participate
- Female of childbearing potential has signed the informed consent about birth defects or attestation on contraception requirements
- Has taken disallowed items (supplement containing vitamin A or beta-carotene, liver-based products, or prescription oral retinoid medications) over the past 30 days
- Is lactating, pregnant, or has a positive serum or urine pregnancy test at screening or at randomization
- Has concurrent medical condition or history, which in the opinion of the investigator, is likely to prevent compliance with the protocol and/or interfere with absorption of ALK-001 or study procedures
- Has clinically significant abnormal laboratory result(s) at screening
- Has active or historical acute or chronic liver disorder
- Has active or historical ocular disorder in the primary study eye that, in the opinion of the investigator, may confound assessment of the retina morphologically or functionally (this could include for example cataract surgery within the past 6 months, choroidal neovascularization (CNV), glaucoma, recurring uveitis, diabetic retinopathy, other retinal disease, etc.)
- Has had intraocular surgery or injections in the primary study eye within 90 days of the screening visit
- Has a clinically significant abnormal electrocardiogram (ECG), or has a corrected QT interval (QTc) that is 450 ms or greater
Primary Outcome Measure
- Safety and tolerability of 24 months of daily dosing of ALK-001 assessed by Incidence and/or clinically significant changes of a combination of ocular and non-ocular adverse events
Secondary Outcome Measures
- Effects of ALK-001 on the progression of Stargardt disease-related changes in atrophic lesion size, best corrected visual acuity (BCVA), and ocular assessments
- Pharmacokinetic profile of ALK-001 derived from the concentrations of ALK-001 and metabolites in plasma
What are Vitamin A Dimers (A2E)
Vitamin A dimers (A2E) are aggregates of vitamin A, which form gradually with age or quickly due to mutations on the ABCA4 gene. On fundus autofluorescence imaging, hyperautofluorescence is associated with increased vitamin A dimers.
Vitamin A dimers are toxic to the retina and have been implicated in the development of AMD and Stargardt disease. Vitamin A dimers have been shown to cause chronic oxidative stress, inflammation, dysregulation of the complement, angiogenesis, poisoning of the lysosomes, etc.
Slowing vitamin A dimerization may prevent blindness associated with conditions such as AMD or Stargardt.
What is ALK-001?
ALK-001 is a modified form of vitamin A, which does not dimerize as readily as natural vitamin A. To synthesize ALK-001, three hydrogen atoms are selectively replaced by three heavy hydrogen (also known as “deuterium”). Deuterium impedes the formation of vitamin A dimers. Because deuterium and hydrogen are similar, ALK-001 preserves the normal biological functions of vitamin A. As such, ALK-001 is not a visual cycle modifier.
ALK-001 prevents age-related degeneration of the retina in various mice models (see References).
In clinical trials, ALK-001 rapidly replaces vitamin A in the body when given once-a-day as a capsule, thereby significantly inhibiting the formation of vitamin A dimers in the retina. In addition to the TEASE studies, ALK-001 is being investigated for the treatment of geographic atrophy associated with age-related macular degeneration.
ALK-001 belongs to the vitamin A class, meaning that side effects if any, would be those normally associated with vitamin A. These side effects are known to resolve upon discontinuation of vitamin A. In previous and ongoing clinical trials, no unexpected adverse events have been observed and all adverse events have been mild or moderate. Based on these clinical data, no serious adverse reactions are expected in the TEASE studies.
TEASE studies are composed of 12 scheduled visits, spanning a total of ~28 months. Eight comprehensive visits (including imaging, clinical lab, and other ocular assessments) take place every 4 to 6 months and may last up to 4 hours. Short visits are scheduled in between comprehensive study visits and last up to 2 hours.
To help defray costs associated with participation in the study, study participants will receive gift cards after each completed visit.
Yes. Patients who have previously enrolled in a clinical trial may participate in TEASE studies upon permission by the sponsor.
Participants should not take tetracycline antibiotics, should avoid taking vitamin A containing supplements (including beta carotene), should avoid consumption of liver and should limit alcohol intake to approximately 2 drinks per day.
The TEASE studies are currently ongoing and enrolling. Clinical sites are spread across the United States.
About the Sponsor
Alkeus Pharmaceuticals is a biopharmaceutical company focused on discovering and developing treatments against serious and untreatable diseases of the eye. Most of the company’s research has been funded by private investors, and through funding of the USA’s Food and Drug Administration (FDA) and the National Eye Institute (NEI) of the National Institutes of Health (NIH). Alkeus Pharmaceuticals is based in Somerville, Massachusetts.
To Contact the Sponsor Please Fill out the Following Form
- Issa PC, Barnard AR, Herrmann P, Washington I, MacLaren RE. Rescue of the Stargardt Phenotype in Abca4 Knockout Mice Through Inhibition of Vitamin A Dimerization, http://www.pnas.org/content/112/27/8415
- Kaufman Y, Ma L, Washington I. Deuterium Enrichment of Vitamin A at the C20 Position Slows the Formation of Detrimental Vitamin A Dimers in Wild-type Rodents, https://www.ncbi.nlm.nih.gov/pubmed/21075840
- Ma L, Kaufman Y, Zhang J, Washington I. C20-D3-vitamin A Slows Lipofuscin Accumulation and Electrophysiological Retinal Degeneration in a Mouse Model of Stargardt Disease, https://www.ncbi.nlm.nih.gov/pubmed/21156790
- Washingon I, Saad L. The Rate of Vitamin A Dimerization in Lipofuscinogenesis, Fundus Autofluorescence, Retinal Senescence and Degeneration, https://www.ncbi.nlm.nih.gov/pubmed/26427431
- Saad L, Washington I. Can Vitamin A be Improved to Prevent Blindness due to Age-Related Macular Degeneration, Stargardt Disease and Other Retinal Dystrophies?, https://www.ncbi.nlm.nih.gov/pubmed/26427432
- Issa PC, Barnard AR, Herrmann P, Washington I, MacLaren RE. Rescue of the Stargardt Phenotype in Abca4 Knockout Mice Through Inhibition of Vitamin A Dimerization.
- Kaufman Y, Ma L, Washington I. Deuterium Enrichment of Vitamin A at the C20 Position Slows the Formation of Detrimental Vitamin A Dimers in Wild-type Rodents.
- Ma L, Kaufman Y, Zhang J, Washington I. C20-D3-vitamin A Slows Lipofuscin Accumulation and Electrophysiological Retinal Degeneration in a Mouse Model of Stargardt Disease.
- Washingon I, Saad L. The Rate of Vitamin A Dimerization in Lipofuscinogenesis, Fundus Autofluorescence, Retinal Senescence and Degeneration.
- Saad L, Washington I. Can Vitamin A be Improved to Prevent Blindness due to Age-Related Macular Degeneration, Stargardt Disease and Other Retinal Dystrophies?,