Safety, Tolerability, Plug Retention and Preliminary Efficacy of Tacrolimus-loaded Punctal Plug in Patients With Moderate to Severe Dry Eye Disease - Cohort B

NCT05618730 | Unknown Phase 1

• 1 other identifier: EXP-TC-1
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this interventional study is to assess safety, patient tolerability, plug retention rate, and preliminary efficacy in improving the symptoms of Dry Eye Disease (DED) of EXP-TC tacrolimus releasing punctal plug. The main questions it aims to answer are:

1. 1.The safety of using EXP-TC plug following all study adverse events
2. 2.The number of patients with Adverse Events related to the us of EXP-LP plug
3. 3.The number of patients discontinuing the study due to plug discomfort
4. 4.The total patients with plugs remained during the 3-months study duration from plug insertion
5. 5.Exploratory: change from baseline in the study eye to follow-up visits in various Dryness clinical measurements. The change of measurements from baseline will also be compared between the study and fellow control eye (receiving artificial tears only, 0.15% sodium hyaluronate).

Conditions

Dry Eye; Keratoconjunctivitis Sicca; Ocular Inflammation

Outcome Measures

Primary Outcomes (2)

• The primary safety endpoint is adverse events' frequency, severity, and duration.

  Main Adverse Event that will be focused on during the study: Irritation and local discomfort Increased Lacrimation Increased mucus Intraocular inflammation Ocular redness Eyelid Edema Hyperemia conjunctival erythema Keratitis

  Will be evaluated through study completion (6 weeks)

• The number of Participants with Treatment-Related Adverse Events

  as assessed by CTCAE v4.0

  Will be evaluated through study completion (6 weeks)

Secondary Outcomes (10)

• Patient Tolerability

  Will be evaluated through study completion (6 weeks)

• Plug retention rate

  Study termination visit: 6 weeks after plug insertion

• Exploratory Endpoint1

  Will be evaluated from baseline to follow up visit 6 (4 weeks from plug insertion)

• Exploratory Endpoint2

  Will be evaluated from baseline to follow up visit 6 (4 weeks from plug insertion)

• Exploratory Endpoint3

  Will be evaluated from baseline to follow up visit 6 (4 weeks from plug insertion)

Study Arms (2)

EXP-TC punctal plug together with artificial tears

EXPERIMENTAL

EXP-TC: A punctal plug as a delivery system for Tacrolimus. EXP-TC has 3 different sizes (Small, Medium and Big for Wide EXP-TC)

Device: punctum plug insertion; Drug: Eye Drops, Lubricant

Artificial tears

ACTIVE COMPARATOR

Preservative-free, 0.15% sodium hyaluronate (Hyabak, Théa laboratories)

Drug: Eye Drops, Lubricant

Interventions

punctum plug insertion DEVICE

EXP-TC delivers the anti-inflammatory drug tacrolimus that acts as inhibitor of T lymphocytes and may therefore lead to the inhibition of release of inflammatory cytokines. EXP-TC has a Pangolin design and has 3 different designs: big, medium and small with drug content ranging from 194 to 348 µg. After plug insertion preservative-free, 0.15% sodium hyaluronate (Hyabak, Théa laboratories) is taken 4 times daily.

EXP-TC punctal plug together with artificial tears

Eye Drops, Lubricant DRUG

Preservative-free, 0.15% sodium hyaluronate (Hyabak, Théa laboratories) 4 times daily.

Artificial tears; EXP-TC punctal plug together with artificial tears

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, 18 years of age and over;
• Patient-reported history of DED in both eyes
• Use of artificial tears within 3 months before the Screening Visit
• Corneal fluorescein staining score ≥2 (0- to 4-point scale) in ≥1 region (superior, inferior, or central) in at least one eye
• Schirmer ≥1 and ≤10 mm in both eyes
• Central corneal thickness of 400-620 microns.
• IOP ≤ 24 mmHg in each eye

You may not qualify if:

• Intolerance or contraindication to Tacrolimus
• Stevens-Johnson Syndrome;
• Use of methotrexate or systemic cyclosporine within the 3 months before the Screening Visit;
• Using systemic anti-rheumatic therapy, if started within 6 months before recruitment OR that the systemic disease is considered unstable OR that the patient is unsure of continuing using the treatment throughout the current study;
• Use of any anti-rheumatic biological agent within 2 months, or 5 half-lives, whichever is longer, before the Screening Visit;
• Use of oral corticosteroids \>10 mg prednisone, or equivalent, per day, if started within 2 months before screening;
• Use of topical steroids within 4 weeks before the Screening Visit and for the duration of the study
• Use of oral statin or preparation containing omega-3 fatty acid unless dose has been stable for at least 3 months and will remain so during the trial;
• Presence of chronic ocular disease other than Aqueous-Deficient Dry Eye requiring topical treatment.
• Presence of post-burn ocular injury;
• Active ocular herpes simplex virus infection;
• Concomitant use of contact lenses or use within 3 months before the Screening Visit or inability to abstain from contact lens use throughout the study.
• Persistent intraocular inflammation or infection;
• Have anterior blepharitis, which is deemed clinically significant and likely to interfere with study parameters in the opinion of the investigator;
• Meibomian gland dysfunction (MGD) necessitating treatment in the 4 weeks before or planned during the study period.

Sponsors & Collaborators

• Eximore Ltd.: lead

Study Sites (1)

Asociación para Evitar la Ceguera en México (APEC)

Mexico City, Coyoacán, 04030, Mexico

Location

Related Publications (9)

• Baldo A, Cafiero M, Di Caterino P, Di Costanzo L. Tacrolimus ointment in the management of atopic dermatitis. Clin Cosmet Investig Dermatol. 2009 Jan 27;2:1-7. doi: 10.2147/ccid.s3378.

  PMID: 21436963 BACKGROUND

• Berdoulay A, English RV, Nadelstein B. Effect of topical 0.02% tacrolimus aqueous suspension on tear production in dogs with keratoconjunctivitis sicca. Vet Ophthalmol. 2005 Jul-Aug;8(4):225-32. doi: 10.1111/j.1463-5224.2005.00390.x.

  PMID: 16008701 BACKGROUND

• Ebihara N, Ohashi Y, Fujishima H, Fukushima A, Nakagawa Y, Namba K, Okamoto S, Shoji J, Takamura E, Uchio E, Miyazaki D. Blood level of tacrolimus in patients with severe allergic conjunctivitis treated by 0.1% tacrolimus ophthalmic suspension. Allergol Int. 2012 Jun;61(2):275-82. doi: 10.2332/allergolint.11-OA-0349. Epub 2012 Feb 25.

  PMID: 22361511 BACKGROUND

• Fukushima A, Ohashi Y, Ebihara N, Uchio E, Okamoto S, Kumagai N, Shoji J, Takamura E, Nakagawa Y, Namba K, Fujishima H, Miyazaki D. Therapeutic effects of 0.1% tacrolimus eye drops for refractory allergic ocular diseases with proliferative lesion or corneal involvement. Br J Ophthalmol. 2014 Aug;98(8):1023-7. doi: 10.1136/bjophthalmol-2013-304453. Epub 2014 Apr 2.

  PMID: 24695688 RESULT

• Haddad EM, McAlister VC, Renouf E, Malthaner R, Kjaer MS, Gluud LL. Cyclosporin versus tacrolimus for liver transplanted patients. Cochrane Database Syst Rev. 2006 Oct 18;2006(4):CD005161. doi: 10.1002/14651858.CD005161.pub2.

  PMID: 17054241 RESULT

• Hanifin JM, Paller AS, Eichenfield L, Clark RA, Korman N, Weinstein G, Caro I, Jaracz E, Rico MJ; US Tacrolimus Ointment Study Group. Efficacy and safety of tacrolimus ointment treatment for up to 4 years in patients with atopic dermatitis. J Am Acad Dermatol. 2005 Aug;53(2 Suppl 2):S186-94. doi: 10.1016/j.jaad.2005.04.062.

  PMID: 16021174 RESULT

• Kanellopoulos AJ, Asimellis G. In pursuit of objective dry eye screening clinical techniques. Eye Vis (Lond). 2016 Jan 18;3:1. doi: 10.1186/s40662-015-0032-4. eCollection 2016.

  PMID: 26783543 RESULT

• Moscovici BK, Holzchuh R, Chiacchio BB, Santo RM, Shimazaki J, Hida RY. Clinical treatment of dry eye using 0.03% tacrolimus eye drops. Cornea. 2012 Aug;31(8):945-9. doi: 10.1097/ICO.0b013e31823f8c9b.

  PMID: 22511024 RESULT

• Reitamo S, Ortonne JP, Sand C, Cambazard F, Bieber T, Folster-Holst R, Vena G, Bos JD, Fabbri P, Groenhoej Larsen C; European Tacrolimus Ointment Study Group. A multicentre, randomized, double-blind, controlled study of long-term treatment with 0.1% tacrolimus ointment in adults with moderate to severe atopic dermatitis. Br J Dermatol. 2005 Jun;152(6):1282-9. doi: 10.1111/j.1365-2133.2005.06592.x.

  PMID: 15948994 RESULT

Related Links

• Treatment of Dry Eye Using 0.03% Tacrolimus Eye Drops
• EagleVision Procedure Demo

MeSH Terms

Conditions

Dry Eye Syndromes; Keratoconjunctivitis Sicca

Interventions

Lubricant Eye Drops

Condition Hierarchy (Ancestors)

Lacrimal Apparatus Diseases; Eye Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases

Intervention Hierarchy (Ancestors)

Ophthalmic Solutions; Pharmaceutical Solutions; Solutions; Pharmaceutical Preparations; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Lubricants; Specialty Uses of Chemicals

Study Officials

• Nallely Ramos Betancourt, Dr.

  Asociación para Evitar la Ceguera en México

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Each patient with Dry Eye Disease is tested with EXP-TC tacrolimus releasing punctal plug in one eye. Both eyes will receive standard of care of 0.15% sodium hyaluronate (Hyabak, Théa laboratories).

Study Record Dates

• First Submitted: November 3, 2022
• First Posted: November 16, 2022
• Study Start: September 29, 2022
• Primary Completion: December 30, 2023
• Study Completion: December 30, 2023
• Last Updated: September 7, 2023

Record last verified: 2023-09

Locations

ME (1)