Phase 3 Study of ALK-001 in Geographic Atrophy

(SAGA Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alkeus Pharmaceuticals, Inc.

Disqualifiers: Medical condition interfering with study, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a special type of vitamin A in people with vision loss due to Geographic Atrophy from age-related macular degeneration. The goal is to see if this vitamin can slow down the damage to the retina by reducing harmful clumps of vitamin A. There are no current treatments for this condition, making this study important for those affected.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It might depend on whether your medications interfere with the study, so it's best to discuss this with the trial coordinators.

What data supports the effectiveness of the drug ALK-001?

The research mentions that synthetic retinoids like fenretinide have shown promising anticancer activity in preclinical studies, and a novel formulation improved its bioavailability, which means the body can use it more effectively. Additionally, some retinoids have shown potential in cancer prevention, although more data is needed. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Alitretinoin, a form of retinoid, has been studied for safety in treating conditions like chronic hand eczema and Kaposi sarcoma. It is generally considered safe, but higher doses may increase the risk of side effects like high triglycerides (a type of fat in the blood). ^{4 6 7 8 9}

What makes the drug ALK-001 unique compared to other treatments?

ALK-001, also known as Gildeuretinol acetate, is a unique treatment because it is a modified form of vitamin A (retinoid) designed to potentially offer benefits in conditions where traditional retinoids may not be effective. Its novel formulation aims to improve bioavailability and effectiveness, which could make it a promising option for conditions resistant to other retinoid treatments. ^{3 4 5 10 11}

Research Team

Leonide Saad, PhD

Principal Investigator

Alkeus Pharmaceuticals, Inc.

Eligibility Criteria

This trial is for people with a condition called Geographic Atrophy (GA) that's due to dry age-related macular degeneration. Participants need to have at least one eye affected by GA. They shouldn't have any health issues that could mess with the study or stop them from following the trial procedures and staying in the study.

Inclusion Criteria

I have dry AMD causing vision loss in at least one eye.

I have vision loss in at least one eye due to dry AMD.

Exclusion Criteria

I do not have any health issues that would stop me from following the study's requirements.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ALK-001 or placebo to evaluate the efficacy and safety in treating Geographic Atrophy

12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• ALK-001
• Placebo oral capsule

Trial Overview The trial is testing ALK-001, an oral capsule, against a placebo (a pill without active medication). It's a phase 3 study where participants are randomly chosen to receive either ALK-001 or placebo, and neither they nor the researchers know who gets what—a method known as double-masking.

Participant Groups

Group I: ALK-001 Experimental Treatment 1 Intervention

Capsule

Group II: Placebo Placebo Group 1 Intervention

Capsule

ALK-001 is already approved in United States for the following indications:

Approved in United States as Gildeuretinol for:

• Stargardt disease

Who Is Running the Clinical Trial?

Alkeus Pharmaceuticals, Inc.

Lead Sponsor

Trials

4

Recruited

520+

Findings from Research

Intravenous liposomal all-trans-retinoic acid (L-ATRA) maintains significantly higher and stable plasma concentrations compared to oral ATRA, with 13- and 22-fold greater AUC values on days 1 and 9, respectively, indicating a more effective delivery method.

Despite higher plasma levels of L-ATRA, the side effects were similar to those of oral ATRA, although L-ATRA was associated with dermal exfoliation in 31% of subjects, while oral ATRA led to abnormal liver function tests in 23% of subjects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of intravenously administered liposomal all-trans-retinoic acid (ATRA) and orally administered ATRA in healthy volunteers. Ozpolat, B., Lopez-Berestein, G., Adamson, P., et al.[2022]

The review of nine retinoids for cancer prevention found that all-trans-retinoic acid, 13-cis-retinoic acid, and N-ethylretinamide are not suitable for human use due to toxicity, potential to enhance cancer, or ineffectiveness.

Conversely, 9-cis-retinoic acid, etretinate, and acitretin show some potential for cancer prevention, but further research is needed, while all-trans N-(4-hydroxyphenyl)retinamide appears particularly promising.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An International Evaluation of the Cancer-Preventive Potential of Nine Retinoids. Miller, AB., Nettesheim, P., Stewart, BW.[2019]

References

1. China pubmed.ncbi.nlm.nih.gov

[The experimental treatment of laryngeal carcinoma with all-trans retinoic acid]. [2013]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of intravenously administered liposomal all-trans-retinoic acid (ATRA) and orally administered ATRA in healthy volunteers. [2022]

3. Greece pubmed.ncbi.nlm.nih.gov

Phase I trial of fenretinide lym-x-sorb oral powder in adults with solid tumors and lymphomas. [2021]

4. Thailand pubmed.ncbi.nlm.nih.gov

An International Evaluation of the Cancer-Preventive Potential of Nine Retinoids. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Fenretinide activity in retinoid-resistant oral leukoplakia. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Topical treatment of cutaneous lesions of acquired immunodeficiency syndrome-related Kaposi sarcoma using alitretinoin gel: results of phase 1 and 2 trials. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of retinoids in women after meal consumption or vitamin A supplementation. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Use of Longitudinal Dose-Response Modeling to Support the Efficacy and Tolerability of Alitretinoin in Severe Refractory Chronic Hand Eczema (CHE). [2018]

9. Saudi Arabia pubmed.ncbi.nlm.nih.gov

The effectiveness of alitretinoin for the treatment of chronic hand eczema: A meta-analysis. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Structure-activity relationships among various retinoids and their ability to inhibit neoplastic transformation and to increase cell adhesion in the C3H/10T1/2 CL8 cell line. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Retinoids as preventive and therapeutic anticancer agents (Part I). [2007]