Cyclosporine + Intense Pulsed Light for Dry Eye Syndrome

(CycliP Trial)

Overseen By Eric Lortie-Milner, OD, FAAO

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Université de Sherbrooke

Must be taking: Cyclosporine

Must not be taking: Photosensitizing, Glaucoma drops

Disqualifiers: Pregnancy, Ocular herpes, Epilepsy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 16 weeks

44 Participants Needed

Trial Summary

What is the purpose of this trial?

In this study, two treatments typically used for dry eye disease will be tried for contact lens users to see if their symptoms when they use their contact lenses get better. Cyclosporine is a drop that is used for long-term management of the inflammation and Intense pulsed light (IPL) is a treatment done in a clinic to improve the health of the eyelid glands. The main question in this study is: Does the combined treatment of cyclosporine and IPL improve the symptoms and the dry eye signs of contact lens wearers? All the participants will receive the cyclosporine drops for 4 months twice a day. The research team will split the group of participants in two, half receiving the real IPL treatment and half receiving a sham IPL treatment during the last two months of the study. This will allow to compare the two groups to see how IPL helped. The dry eye tests will be done at the start of the study, after two months and after 4 months. The tests will include a dry eye symptoms questionnaire, measures on the tears, the structures of the front of the eye and the eyelids.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have used cyclosporine eye drops recently or are using photosensitizing medication.

What data supports the effectiveness of the treatment Cyclosporine + Intense Pulsed Light for Dry Eye Syndrome?

Research shows that cyclosporine 0.05% has been effective in treating dry eye disease and other eye conditions with an immune-based inflammatory component. It has been approved by the FDA for dry eye disease and has shown positive results in managing conditions like ocular rosacea and post-LASIK dry eye. ^{1 2 3 4 5}

Is the combination of Cyclosporine and Intense Pulsed Light safe for treating dry eye syndrome?

Research on cyclosporine for dry eye disease shows it is generally safe, with common side effects like burning or stinging in the eyes. However, there is no specific safety data available for the combination of cyclosporine and intense pulsed light. ^{3 4 6 7 8}

How is the drug cyclosporine unique in treating dry eye syndrome?

Cyclosporine is unique because it is an anti-inflammatory drug that specifically targets the immune system to reduce inflammation on the eye's surface, making it effective for dry eye syndrome and other immune-related eye conditions. It is available as a topical emulsion, which is a non-toxic alternative to other potentially harmful treatments. ^{1 2 4 6 7}

Research Team

Patrick Boissy, PhD

Principal Investigator

Professor University of Sherbrooke

Langis Michaud, OD, MSc

Principal Investigator

Professor University of Montreal

Eric Lortie-Milner, OD

Principal Investigator

PhD candidate University of Sherbrooke

Eligibility Criteria

This trial is for contact lens users who suffer from dry eye syndrome. Participants should be willing to use cyclosporine drops twice daily and undergo IPL treatments. Those with certain eye conditions or who have had recent eye surgery may not qualify.

Inclusion Criteria

Soft silicone-hydrogel contact lens wearers

f-CLDEQ-8 score ≥ 12

I change my contact lenses daily, every 2 weeks, or monthly.

Exclusion Criteria

Known intolerance to cyclosporine

I currently have an eye infection.

Excessive movement or decentration of the contact lenses (assessed at first visit)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 0.09% cyclosporine drops twice a day for 16 weeks. In the last 2 months, participants receive either real or sham IPL treatment.

16 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cyclosporine
• Intense Pulsed Light
• Sham Intense Pulse Light

Trial Overview The study tests if using cyclosporine eye drops in combination with Intense Pulsed Light (IPL) therapy can improve dry eyes in contact lens wearers, compared to those only using the drops and receiving a sham IPL treatment.

Participant Groups

Group I: IPL group Experimental Treatment 2 Interventions

Participants will receive 0.09% cyclosporine drops dosed at bid for 16 weeks. Participants receive 3 IPL sessions at 3-weeks interval in the last 2 months of the study. IPL treatments will be given with Lumenis M22 with a 590nm filter, pulse duration of 6-50ms (3 pulses/trigger) and fluence will be determined after determining the skin type (Fitzpatrick scale) of the participant.

Group II: Sham-IPL group Placebo Group 2 Interventions

Participants will receive 0.09% cyclosporine drops dosed at bid for 16 weeks. Participants receive 3 IPL sessions at 3-weeks interval in the last 2 months of the study. IPL treatments will be given with Lumenis M22 with a 590nm filter, pulse duration of 6-50ms (3 pulses/trigger) and fluence will be determined set at 10 J/cm2. A plastic filter will recover the IPL prism, preventing the light to reach the skin of the participant.

Cyclosporine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Neoral for:

• Prevention of organ rejection in kidney, liver, heart, lung, pancreas, and bone marrow transplants
• Treatment of severe psoriasis
• Treatment of nephrotic syndrome

Approved in United States as Neoral for:

• Prevention of organ rejection in kidney, liver, and heart transplants
• Treatment of severe rheumatoid arthritis
• Treatment of severe psoriasis

Approved in Canada as Neoral for:

• Prevention of organ rejection in kidney, liver, heart, lung, pancreas, and bone marrow transplants
• Treatment of severe psoriasis
• Treatment of nephrotic syndrome

Approved in Japan as Neoral for:

• Prevention of organ rejection in kidney, liver, and heart transplants
• Treatment of severe rheumatoid arthritis
• Treatment of severe psoriasis

Who Is Running the Clinical Trial?

Université de Sherbrooke

Lead Sponsor

Trials

317

Recruited

79,300+

Findings from Research

In a study of 25 long-term contact lens wearers with dry eye syndrome, cyclosporine emulsion 0.05% significantly improved tear film stability and basal tear secretion over 6 months, with increases of 37.3% and 82.4%, respectively.

The treatment also enhanced contact lens tolerance and restored corneal epithelial structure, indicating that cyclosporine emulsion can effectively address symptoms of dry eye in patients unresponsive to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Topical cyclosporine for the treatment of ocular surface changes in contact lens wearers]. Egorova, GB., Mitichkina, TS., Fedorov, AA., et al.[2018]

Cyclosporine 0.05% ophthalmic emulsion, approved by the FDA in 2003, is effective in treating dry eye disease and has shown efficacy in managing various ocular surface disorders with an immune-based inflammatory component.

This topical formulation serves as a safe and non-toxic alternative to other potentially harmful immunosuppressive therapies, making it a valuable option for patients with conditions like posterior blepharitis and ocular rosacea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical ophthalmic cyclosporine: pharmacology and clinical uses. Donnenfeld, E., Pflugfelder, SC.[2022]

Topical cyclosporine 0.05% (Restasis) significantly improved dry eye symptoms in 7 out of 8 patients with graft versus host disease after stem cell transplantation, indicating its efficacy for this specific condition.

The treatment led to statistically significant improvements in key measures of dry eye, including tear production and stability, as evidenced by Schirmer scores, tear breakup time, and tear lysozyme levels, suggesting a beneficial mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of topical cyclosporine 0.05% in the treatment of dry eye associated with graft versus host disease. Rao, SN., Rao, RD.[2015]

In a study of 64 individuals with dry eye disease, a greater number preferred cyclosporine A (CsA) 0.05% over lifitegrast 5%, with 33 preferring CsA compared to 14 for lifitegrast.

No specific demographic or clinical factors were found to influence medication preference, suggesting that individual responses to these treatments may vary widely regardless of patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Subjective Responses to Cyclosporine 0.05% Versus Lifitegrast 5.0% in Individuals With Dry Eye Disease. Locatelli, EVT., Acuna, KA., Betz, J., et al.[2023]

In a study involving 412 patients with moderate to severe dry eye disease, cyclosporine 0.1% ophthalmic emulsion was found to be safe and well tolerated over a treatment period of up to 3 years, with no serious treatment-related adverse events reported.

While improvements in dry eye symptoms were modest, most patients (95.2%) expressed a desire to continue treatment, indicating a positive overall experience with the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III safety evaluation of cyclosporine 0.1% ophthalmic emulsion administered twice daily to dry eye disease patients for up to 3 years. Barber, LD., Pflugfelder, SC., Tauber, J., et al.[2022]

A survey of 21 physicians treating dry eye disease revealed low satisfaction with the effectiveness and onset of action of the anti-inflammatory treatments cyclosporine (CYC) and lifitegrast (LIF), despite two-thirds expressing overall satisfaction with these medications.

Physicians reported that common side effects included burning sensations and dysgeusia, and emphasized a strong need for more effective treatment options for dry eye disease, as fewer than half found CYC and LIF effective in improving patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physician Satisfaction with Anti-Inflammatory Topical Medications for the Treatment of Dry Eye Disease. White, DE., Zhao, Y., Jayapalan, H., et al.[2022]

In a phase III trial involving 627 participants, CyclAGel 0.05% significantly improved symptoms of moderate-to-severe dry eye disease compared to a vehicle, with 73.7% of patients showing at least a 1-point improvement in the ICSS scale by day 84.

CyclAGel was well tolerated, with mostly mild side effects, and no serious treatment-related adverse events reported, making it a safe and effective once-daily treatment option for dry eye disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclosporine A (0.05%) Ophthalmic Gel in the Treatment of Dry Eye Disease: A Multicenter, Randomized, Double-Masked, Phase III, COSMO Trial. Peng, W., Jiang, X., Zhu, L., et al.[2022]

A systematic review of 26 trials involving 13 topical ophthalmic drugs for dry eye disease (DED) found that while lifitegrast showed statistical superiority in symptom or sign endpoints in large trials, no other large studies demonstrated significant results for both signs and symptoms compared to controls.

Common side effects of these approved drugs included ocular discomfort, such as burning and stinging, highlighting the need for better standardization in clinical trial designs for DED treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of topical ophthalmic drugs in the treatment of dry eye disease: A systematic literature review. Holland, EJ., Darvish, M., Nichols, KK., et al.[2020]

References

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Topical cyclosporine for the treatment of ocular surface changes in contact lens wearers]. [2018]

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

Topical ophthalmic cyclosporine: pharmacology and clinical uses. [2022]

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

Efficacy of topical cyclosporine 0.05% in the treatment of dry eye associated with graft versus host disease. [2015]

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

Comparison of Subjective Responses to Cyclosporine 0.05% Versus Lifitegrast 5.0% in Individuals With Dry Eye Disease. [2023]

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

Phase III safety evaluation of cyclosporine 0.1% ophthalmic emulsion administered twice daily to dry eye disease patients for up to 3 years. [2022]

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

Physician Satisfaction with Anti-Inflammatory Topical Medications for the Treatment of Dry Eye Disease. [2022]

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

Cyclosporine A (0.05%) Ophthalmic Gel in the Treatment of Dry Eye Disease: A Multicenter, Randomized, Double-Masked, Phase III, COSMO Trial. [2022]

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

Efficacy of topical ophthalmic drugs in the treatment of dry eye disease: A systematic literature review. [2020]