A Multi-Center, Double-Masked, Randomized, Vehicle-Controlled, Parallel-Group Clinical Trial Evaluating the Safety of Reproxalap Ophthalmic Solution in Subjects With Dry Eye Disease

Overseen By Bill Cavanagh

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Aldeyra Therapeutics, Inc.

Must not be taking: Cyclosporine, Lifitegrast

Disqualifiers: Blepharitis, MGD, Ocular infection, 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: 6 weeks

757 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use certain eye drops like cyclosporine or lifitegrast within 90 days before starting the trial. You also cannot use any eye drops within 2 hours of your first visit.

What data supports the effectiveness of the drug Reproxalap Ophthalmic Solution?

Research shows that Reproxalap, a novel RASP inhibitor, significantly improves symptoms of dry eye disease, such as discomfort and tear quality, within a week of use. It has been tested in multiple trials and demonstrated safety and effectiveness in reducing dry eye symptoms. ^{1 2 3 4 5}

Is Reproxalap safe for use in humans?

Research on Reproxalap, used for dry eye disease, shows no significant safety concerns in clinical trials, suggesting it is generally safe for human use. ^{1 2 3 4 5}

How does the drug Reproxalap Ophthalmic Solution differ from other treatments?

Reproxalap Ophthalmic Solution is unique because it is an ophthalmic (eye) solution, which means it is administered directly to the eye, potentially reducing systemic side effects compared to oral medications. This localized delivery can be beneficial for conditions affecting the eyes, as it targets the area directly without affecting the rest of the body. ^{6 7 8 9 10}

What is the purpose of this trial?

This trial is testing eye drops containing Reproxalap to see if they are safe for people with dry eyes. The drops aim to reduce swelling and discomfort in the eyes. The study involves multiple centers and compares the eye drops to another treatment. Reproxalap is being tested for its safety and effectiveness in treating dry eye disease.

Eligibility Criteria

Inclusion Criteria

Reported history of dry eye for at least 6 months prior to Visit 1;

History of use or desire to use eye drops for dry eye symptoms within 6 months of Visit 1.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Reproxalap or vehicle four times daily for four weeks followed by two times daily for two weeks

6 weeks

Extended Treatment

Participants continue receiving Reproxalap or vehicle two times daily for an additional 11 months

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo Comparator
• Reproxalap Ophthalmic Solution

Participant Groups

Group I: Reproxalap (0.25%) for six weeks Experimental Treatment 1 Intervention

Reproxalap four times daily (QID) for four weeks followed by two times daily (BID) for two weeks

Group II: Reproxalap (0.25%) for 12 months Experimental Treatment 1 Intervention

Reproxalap (0.25%) QID for four weeks followed by BID for 11 months

Group III: Vehicle for six weeks Placebo Group 1 Intervention

Vehicle QID for four weeks followed by BID for two weeks

Group IV: Vehicle for 12 months Placebo Group 1 Intervention

Vehicle QID for four weeks followed by BID for 11 months

Who Is Running the Clinical Trial?

Aldeyra Therapeutics, Inc.

Lead Sponsor

Trials

34

Recruited

4,700+

Findings from Research

In a clinical trial involving 19 patients with dry eye disease, both formulations of reproxalap demonstrated significantly better comfort and fewer side effects compared to lifitegrast, particularly in terms of ocular discomfort, blurry vision, and dysgeusia.

Reproxalap not only resulted in lower rates of negative responses but also had shorter durations of these responses, suggesting it may enhance patient adherence to treatment due to a more favorable overall experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Post-Acute Ocular Tolerability Comparison of Topical Reproxalap 0.25% and Lifitegrast 5% in Patients with Dry Eye Disease. McMullin, D., Clark, D., Cavanagh, B., et al.[2022]

In a review of 200 randomized drug trials published in 2013, only 1 trial (0.5%) used an active placebo, indicating that these control groups are rarely employed in clinical research.

Active placebos are more commonly found in trials involving drugs with noticeable side effects, as they help reduce the risk of unblinding, although they also carry the risk of causing unintended therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active placebo control groups of pharmacological interventions were rarely used but merited serious consideration: a methodological overview. Jensen, JS., Bielefeldt, AØ., Hróbjartsson, A.[2018]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

A Post-Acute Ocular Tolerability Comparison of Topical Reproxalap 0.25% and Lifitegrast 5% in Patients with Dry Eye Disease. [2022]

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

Early Onset and Broad Activity of Reproxalap in a Randomized, Double-Masked, Vehicle-Controlled Phase 2b Trial in Dry Eye Disease. [2021]

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

Lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease: results of the OPUS-1 phase 3 study. [2022]

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

A Randomized Double-Masked Phase 2a Trial to Evaluate Activity and Safety of Topical Ocular Reproxalap, a Novel RASP Inhibitor, in Dry Eye Disease. [2021]

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

Acute and chronic ocular symptoms of dorzolamide 2% compared with placebo. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Sildenafil in women with sexual arousal disorder following spinal cord injury. [2015]

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

Active placebo control groups of pharmacological interventions were rarely used but merited serious consideration: a methodological overview. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Intraocular pressure efficacy of glaucoma medications versus placebo in phase II compared to later phase trials. [2013]

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

Sequential bioactivation of methoxime analogs of beta-adrenergic antagonists in the eye. [2007]

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

Improved postoperative pain control in pediatric adenotonsillectomy with dextromethorphan. [2013]