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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining cyclosporine drops with Intense Pulsed Light (IPL) can improve dry eye symptoms in contact lens wearers. Cyclosporine manages eye inflammation, while IPL, a clinic-based treatment, aims to enhance eyelid gland health. All participants will use cyclosporine drops, but only some will receive actual IPL treatments to determine its effectiveness. Ideal candidates for this trial regularly wear soft silicone-hydrogel contact lenses and experience discomfort or dryness. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment for dry eye symptoms.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cyclosporine eye drops are generally safe. Large studies have found no serious side effects from these drops, which are often used to reduce inflammation in people with dry eye disease.

For Intense Pulsed Light (IPL) treatment, studies have demonstrated its effectiveness in improving the stability of the tear film in the eyes. Importantly, these studies have reported no significant side effects. IPL, performed in clinics, is usually well-tolerated by patients.

Overall, the combination of cyclosporine drops and IPL treatment has been studied for safety, with no major safety concerns reported. This makes these treatments a potentially safe option for improving dry eye symptoms. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of cyclosporine and intense pulsed light (IPL) therapy for dry eye syndrome because it offers a novel approach compared to standard treatments like artificial tears and anti-inflammatory eye drops. Unlike traditional therapies, IPL therapy targets the underlying inflammation and meibomian gland dysfunction by using light pulses to improve gland function. This combination could potentially enhance the effectiveness of cyclosporine drops, which work by reducing inflammation on the eye's surface. By addressing both inflammation and gland dysfunction, this treatment could offer improved relief for those suffering from dry eye syndrome.

What evidence suggests that this trial's treatments could be effective for dry eye syndrome?

Research has shown that cyclosporine eye drops can reduce inflammation and improve symptoms for people with dry eye disease. Studies have found that using these drops twice a day for several weeks can increase tear production and reduce dryness. In this trial, participants will receive cyclosporine drops alongside either intense pulsed light (IPL) therapy or a sham IPL treatment. IPL therapy has improved the health of eyelid glands and stabilized tears, aiding dry eye relief. When combined, IPL and cyclosporine effectively relieve dry eye symptoms, especially in conditions like Sjögren's syndrome. This combination may also benefit those with dry eye related to contact lens use. ^{1 3 4 6 7}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06392438

Cyclosporine and Intense Pulsed Light for Dry Eye in ... The main objective of this study is to establish if the treatment of contact lens related dry eyes by the combination of 0.09% cyclosporine for 16 weeks and a ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38785065/

The effect of intense pulsed light combined with topical ... This study aimed to assess the effectiveness and safety of intense pulsed light (IPL) therapy plus topical 0.05% cyclosporine A (CsA) eye drops to treat Sjö ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10276661/

Efficacy of intense pulsed light therapy on signs and ... This study reviewed the efficacy and safety of intense pulsed light (IPL) for the treatment of dry eye disease (DED).

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1542012423001337

Safety and efficacy of intense pulsed light in the treatment ... IPL treatment can effectively increase tear film stability in patients with severe coGVHD without significant side effects.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03194698

Efficacy of IPL Treatment of Dry Eye and Ocular Rosacea Research has shown improvement in patient symptoms with the use of MGX. Intense pulsed light (IPL) have been used in dermatology to treat various conditions.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4298157/

Intense Pulsed Light Treatment for Dry Eye Disease Due to ... The objective of this retrospective noncomparative interventional case series study is to describe clinical data concerning effectiveness and safety of IPL skin ...

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/38/NCT06392438/ICF_001.pdf

The combination of 0.09% Cyclosporine and Intense ... will be offered an eye lubricant for relief. 227. 228. Treatment with Cequa drops has been shown to be safe in large-scale studies. No serious.