Phase 2/3 Study of ALK-001 in Geographic Atrophy (SAGA)

A Phase 2/3 Multicenter, Randomized, Double-masked, Parallel-group, Placebo-controlled Study to Investigate the Safety, Pharmacokinetics, Tolerability, and Efficacy of ALK-001 in Geographic Atrophy Secondary to Age-related Macular Degeneration

This is a double-masked, multicenter, randomized, placebo-controlled clinical trial, evaluating the efficacy and safety of ALK-001 in participants with Geographic Atrophy (GA) secondary to age-related macular degeneration (AMD).

Up to 200 participants will receive ALK-001 while up to 100 participants will receive a placebo.

Study Overview

• Status: Completed
• Conditions: Geographic Atrophy; Age Related Macular Degeneration; AMD; Atrophy, Geographic
• Intervention / Treatment: Drug: ALK-001 oral capsule; Drug: Placebo oral capsule

Detailed Description

There is no oral treatment available for Geographic Atrophy secondary to AMD. AMD is characterized by an age-related degeneration of the retina.

The root cause for this degeneration or why some people develop AMD while others do not, is unknown. Over 20 years ago, it was hypothesized that the dimerization of vitamin A may be a significant contributor to the etiology of AMD. The eye indeed uses vitamin A as a cofactor to sense light, and a striking chemical signature of the aging and degenerating retina is the accumulation of vitamin A dimers in the retinal pigment epithelium (RPE) and the underlying Bruch's membrane. In rodent models, high levels of vitamin A dimers correlate with poor retinal health, and a variety of mechanisms have been proposed by which vitamin A dimers may induce retinal toxicity. It has been argued that these mechanisms participate in the development and progression of AMD.

ALK-001, the study drug, is a modified form of vitamin A. When taken once a day as a capsule, it replaces natural vitamin A in the body with one that forms vitamin A dimers more slowly. This study will measure the extent to which treatment with ALK-001 slows the progression of Geographic Atrophy.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Alkeus Site
  • California
    • Beverly Hills, California, United States, 90211
      • Alkeus Site
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Alkeus Site
  • Florida
    • Clearwater, Florida, United States, 33761
      • Alkeus Site
    • Fort Myers, Florida, United States, 33912
      • Alkeus Site
    • Gainesville, Florida, United States, 32601
      • Alkeus Site
    • Tampa, Florida, United States, 33609
      • Alkeus Site
    • Winter Haven, Florida, United States, 33880
      • Alkeus Site
  • Illinois
    • Bloomington, Illinois, United States, 61704
      • Alkeus Site
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Alkeus Site
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Alkeus Site
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • Alkeus Site
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Alkeus Site
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Alkeus Site
  • New Jersey
    • Northfield, New Jersey, United States, 08225
      • Alkeus Site
  • New York
    • Great Neck, New York, United States, 11021
      • Alkeus Site
    • Hauppauge, New York, United States, 11788
      • Alkeus Site
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Alkeus Site
  • Oregon
    • Ashland, Oregon, United States, 97520
      • Alkeus Site
  • Texas
    • Houston, Texas, United States, 77025
      • Alkeus Site
    • San Antonio, Texas, United States, 78240
      • Alkeus Site-1
    • San Antonio, Texas, United States, 78240
      • Alkeus Site-2
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Alkeus Site
  • Washington
    • Silverdale, Washington, United States, 98383
      • Alkeus Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 56 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Major Inclusion Criteria:

- At least one eye with geographic atrophy secondary to dry age-related macular degeneration (AMD)

Major Exclusion Criteria:

- Medical condition, which may interfere with the progression of GA, prevent performance of study procedures, compliance with protocol, or continuous participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALK-001; Capsule	Drug: ALK-001 oral capsule; Daily administration for 24 months; Other Names: C20-D3-Retinyl Acetate; C20 Deuterated vitamin A
Placebo Comparator: Placebo; Capsule	Drug: Placebo oral capsule; Daily administration for 24 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Growth Rate of GA Lesions, as Assessed by Fundus Autofluorescence (FAF)	Baseline to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events		Baseline to 24 months
Changes in Visual Acuity	Changes in LLVA and BCVA	Baseline to 24 months

Collaborators and Investigators

• Sponsor: Alkeus Pharmaceuticals, Inc.
• Investigators: Study Director: Leonide Saad, PhD, Alkeus Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• 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. J Biol Chem. 2011 Mar 11;286(10):7958-7965. doi: 10.1074/jbc.M110.178640. Epub 2010 Nov 12.
• Mihai DM, Jiang H, Blaner WS, Romanov A, Washington I. The retina rapidly incorporates ingested C20-D(3)-vitamin A in a swine model. Mol Vis. 2013 Jul 25;19:1677-83. Print 2013.
• Saad L, Washington I. Can Vitamin A be Improved to Prevent Blindness due to Age-Related Macular Degeneration, Stargardt Disease and Other Retinal Dystrophies? Adv Exp Med Biol. 2016;854:355-61. doi: 10.1007/978-3-319-17121-0_47.
• Evans JR, Lawrenson JG. Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration. Cochrane Database Syst Rev. 2023 Sep 13;9(9):CD000254. doi: 10.1002/14651858.CD000254.pub5.

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2019
• Primary Completion (Actual): July 25, 2023
• Study Completion (Actual): June 30, 2024

Study Registration Dates

• First Submitted: February 15, 2019
• First Submitted That Met QC Criteria: February 18, 2019
• First Posted (Actual): February 19, 2019

Study Record Updates

• Last Update Posted (Estimated): November 3, 2025
• Last Update Submitted That Met QC Criteria: October 16, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Diseases; Retinal Degeneration; Macular Degeneration; Geographic Atrophy; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Micronutrients; Protective Agents; Vitamins; Adjuvants, Immunologic; Anticarcinogenic Agents; Vitamin A; Retinol acetate
• Other Study ID Numbers: ALK001-P3001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No