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

• ClinicalTrials.gov Identifier: NCT03845582
• Recruitment Status: Active, not recruiting
• First Posted: February 19, 2019
• Last Update Posted: February 16, 2022
• Sponsor: Alkeus Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Alkeus Pharmaceuticals, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Geographic Atrophy; Age Related Macular Degeneration; AMD; Atrophy, Geographic	Drug: ALK-001 oral capsule; Drug: Placebo oral capsule	Phase 3

Detailed Description:

There is no 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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 7, 2019
• Estimated Primary Completion Date: August 31, 2023
• Estimated Study Completion Date: September 30, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Growth rate of GA lesions, as assessed by Fundus Autofluorescence (FAF) [ Time Frame: Baseline to 24 months ]

Secondary Outcome Measures :

1. Safety and tolerability, as assessed by evaluation of adverse events [ Time Frame: Baseline to 24 months ]
2. Pharmacokinetics, as assessed by plasma concentrations of ALK-001 and metabolites [ Time Frame: Baseline to 24 months ]
3. Incidence of choroidal neovascularization (CNV) [ Time Frame: Baseline to 24 months ]
4. Changes in Visual Acuity [ Time Frame: Baseline to 24 months ]
5. Changes in Reading Speed [ Time Frame: Baseline to 24 months ]

Eligibility Criteria

• Ages Eligible for Study: 60 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Massachusetts

Coordinating Center

Somerville, Massachusetts, United States, 02144

Sponsors and Collaborators

Alkeus Pharmaceuticals, Inc.

Investigators

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

More Information

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.

• Responsible Party: Alkeus Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03845582
• Other Study ID Numbers: ALK001-P3001
• First Posted: February 19, 2019
• Last Update Posted: February 16, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Geographic Atrophy; Atrophy; Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; Pathological Conditions, Anatomical; Vitamin A; Retinol acetate; Vitamins; Micronutrients; Physiological Effects of Drugs; Protective Agents; Anticarcinogenic Agents; Antineoplastic Agents; Adjuvants, Immunologic; Immunologic Factors