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Providers2019-02-11T14:34:15+00:00

SAGA Overview

SAGA is a Phase 2/3 multicenter, randomized, double-masked, parallel group, placebo-controlled clinical trial to investigate the safety, pharmacokinetics, tolerability and efficacy of ALK-001 in geographic atrophy secondary to age-related macular degeneration

Main Eligibility Criteria

Inclusion

  1. At least one eye (“study eye”) has GA secondary to AMD
  2. Fellow eye has a history of or active CNV, GA or intermediate AMD
  3. Male or Female 60 years or older

Exclusion

  1. A medical condition, which may interfere with progression of GA, prevent performance of study procedures, compliance with protocol, or continuous participation in the study
  2. Prior enrollment in a previous GA clinical study unless approved by sponsor or if there is documented evidence that subject received placebo or was in the sham group of the previous study

Outcome Measures

Primary Outcome Measure

  1. Growth rate of GA lesions, as assessed by Fundus Autofluorescence (FAF)

Secondary Outcome Measures

  1. Safety and tolerability, assessed by evaluation of treatment emergent adverse events
  2. Secondary efficacy measures, as assessed by incidence of choroidal neovascularization (CNV), changes in Best Corrected Visual Acuity (BCVA), reading speed, and questionnaires
  3. Pharmacokinetics, as assessed by plasma concentrations of ALK-001 and metabolites

About ALK-001

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 modified form of vitamin A, which does not dimerize as readily. 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 SAGA study,  ALK-001 clinical studies are underway for the treatment of Stargardt disease.

About ALK-001

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.

Vitamin A dimers are toxic to the retina and have been implicated in the development of AMD and Stargardt disease. For example, 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 modified form of vitamin A, which does not dimerize as readily. To synthesize ALK-001, three hydrogen atoms are selectively replaced by three heavy hydrogen (also known as “deuterium”), which impedes the formation of vitamin A dimers. Because deuterium and hydrogen are similar, ALK-001 preserves 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 publications).

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 SAGA, ALK-001 clinical studies are underway for the treatment of Stargardt disease.

FAQ

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 SAGA study.

SAGA is composed of 10 scheduled visits, spanning a total of ~24 months. Five comprehensive visits (including imaging, clinical lab, and other ocular assessments) take place every 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 can participate in SAGA, for as long as there is documentation that they have received placebo or have been in the sham group of the previous study(ies), or 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. Use of AREDS2 is recommended.

Patients with active or a history of CNV can enroll for as long as they have one eye with “pure GA.” Participants who develop CNV during the study can continue participation and will receive standard of care treatment for CNV.

The SAGA study is expected to start enrolling participants in the first half of 2019. Clinical sites are spread across the United States.

To refer patients, please contact the sponsor research team who will direct you to the site and investigator closest to you:

  • Telephone: 800-287-2755
  • Emailinfo@sagastudy.com
  • Contact form: Complete the contact form below

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    References

    1. 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
    2. 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
    3. 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
    4. 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
    5. 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