Ikervis for DED Due to GVHD Post Allo-HSCT (Ikervis)

Ikervis for Prophylaxis of Dry Eye Disease Due to Graft vs Host Disease Post Allogeneic Haemtopoietic Stem Cell Transplant

Dry eye disease (DED) is a common sequelae of graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Since Ikervis is reported to be a safe and efficacious treatment of DED associated with chronic GVHD, our study would like to study the efficacy of prophlactic Ikervis in preventing ocular GVHD development.

Study Overview

• Status: Unknown
• Conditions: Leukemia (Both ALL and AML); MDS-EB-1
• Intervention / Treatment: Drug: Cyclosporine Ophthalmic

Detailed Description

This is a prospective single arm interventional study.

The recruitment period will be over 12-18 months to enroll all suitable patients. The total duration of prophylaxis will be for 1 year. After completion of the period of prophylaxis, the patients will be followed up as a non-study patient as clinically indicated.

Forty subjects, undergoing allo-HSCT, will be recruited from the Singapore National Eye Centre upon referral from the Department of Hematology, Singapore General Hospital and followed up at least 5 times over a period of 12 months at the Singapore Eye Research Institute.

The images of the subject eyes will be recorded and stored electronically. These images (corneal fluorescein staining score, Lipiview, meibography, conjunctival redness, tear stability assessment) will be used in the analysis of outcome measures. The Lipiview result is in video format.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Li Lim; Phone Number: 63224500; Email: lim.li@singhealth.com.sg

Study Locations

• Singapore
  • Singapore, Singapore
    • Recruiting
    • Singapore Eye Research Institute
    • Contact: Li Lim; Phone Number: 63224500; Email: lim.li@singhealth.com.sg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 95 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 13 and above
• Able to give informed consent

Exclusion Criteria:

• Presence of concurrent disease
• Unable to complete the follow up

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Single arm; Ikervis (cyclosporine 0.1%), emulsion, one drop into both eyes, once at night.	Drug: Cyclosporine Ophthalmic; Prospective interventional study (single arm); Other Names: Ikervis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess change in basline visual acuity using LogMAR chart with prophylactic Ikervis after 3 to 5 weeks before Haematopoietic Stem Cell Transplant and 3 months, 6 months and 12 months post Haematopoietic Stem Cell Transplant.	Visual acuity will be assessed using LogMAR chart at baseline screening and 3, 6, and 12 months post-HSCT after prophylactic Ikervis.	Baseline, 3 months, 6 months and 1 year post-HSCT follow up
To assess change in baseline intraocular pressure using non-contact tonometry with 3 months, 6 months and 12 months post Haematopoietic Stem Cell Transplant.	Intraocular pressure (mmHg) will be assessed using non-contact tonometry at baseline screening and 3, 6, and 12 months post-HSCT after prophylactic Ikervis.	Baseline, 3 months, 6 months and 1 year post-HSCT follow up
To assess change in baseline anterior ocular health using slit lamp examination with 12 months post Haematopoietic Stem Cell Transplant.	Slit lamp examination will be performed at baseline screening and 12 months post-HSCT after prophylactic Ikervis. Clinical findings such as macroerosions or chemosis on cornea, or cataract will be recorded.	Baseline screening and 1 year post-HSCT follow up
To assess change in baseline posterior ocular health using fundus examination with 12 months post Haematopoietic Stem Cell Transplant.	Fundus examination will be performed at baseline screening and 12 months post-HSCT after prophylactic Ikervis. Clinical findings such as cup disc ratio will be graded from 0.0 to 1.0 (greater value means larger cup), hemorrhage, edema of the retina/macular will be recorded.	Baseline screening and 1 year post-HSCT follow up
To assess change of baseline dry eye symptoms with prophylactic Ikervis after 3 to 5 weeks before Haematopoietic Stem Cell Transplant and 3 months, 6 months and 12 months post Haematopoietic Stem Cell Transplant.	Dry eye symptoms will be assessed using SPEED questionnaire (in score 0-28). A higher score means worse dry eye symptom. The change of dry eye symptoms will be assess from baseline before prophylactic Ikervis, 3 to 5 weeks from baseline (Pre-HSCT), and 3, 6, and 12 months post-HSCT after prophylactic Ikervis.	Baseline, 3 to 5 weeks from baseline (Pre-HSCT), 3 months, 6 months and 1 year post-HSCT follow up
To assess change of baseline non-invasive tear break up time with prophylactic Ikervis after 3 to 5 weeks before Haematopoietic Stem Cell Transplant and 3 months, 6 months and 12 months post Haematopoietic Stem Cell Transplant.	Non-invasive tear break up time (in seconds) will be assessed using Oculus Keratography K5M. The change of NITBUT will be assessed from baseline before prophylactic Ikervis, pre-HSCT, and 3, 6, and 12 months post-HSCT after prophylactic Ikervis.	Baseline, 3 to 5 weeks from baseline (Pre-HSCT), 3 months, 6 months and 1 year post-HSCT follow up
To assess change of baseline conjunctival redness with prophylactic Ikervis after 3 to 5 weeks before Haematopoietic Stem Cell Transplant and 3 months, 6 months and 12 months post Haematopoietic Stem Cell Transplant.	Conjunctival Redness (in grading 0-4) will be assessed using Oculus Keratography K5M. A higher grading means conjunctiva is more red. The change of conjunctival redness will be assessed from baseline before prophylactic Ikervis, pre-HSCT, and 3, 6, and 12 months post-HSCT after prophylactic Ikervis.	Baseline, 3 to 5 weeks from baseline (Pre-HSCT), 3 months, 6 months and 1 year post-HSCT follow up
To assess change of baseline tear lipid thickness with prophylactic Ikervis 12 months post Haematopoietic Stem Cell Transplant.	Tear lipid thickness will be measured using LipiView. The change of tear lipid thickness will be only be assessed from baseline before prophylactic Ikervis and 12 months post-HSCT after prophylactic Ikervis.	Baseline and 1 year post-HSCT follow up
To assess change of baseline Meibomian gland status with prophylactic Ikervis 12 months post Haematopoietic Stem Cell Transplant.	Meibomian gland (in grade 0-3) will be assessed using Infra-red Meibography. We will grade the Meibomian gland disease as: 0, no loss of meibomian glands; 1, lost area was less than one third of the total area of meibomian glands; 2, lost area was between one third and two thirds of the total area of meibomian glands; 3, lost area was over two thirds of the total area of meibomian glands. The change of meibomian gland will be assessed from baseline before prophylactic Ikervis pre-HSCT and 12 months post-HSCT after prophylactic Ikervis.	Baseline and 1 year post-HSCT follow up
To assess change of baseline tear cytokines with prophylactic Ikervis after 3 to 5 weeks after 3 to 5 weeks before Haematopoietic Stem Cell Transplant and 3 months, 6 months and 12 months post Haematopoietic Stem Cell Transplant.	Tear cytokine will be analysed with tears extracted from Schirmers test. The change of tear cytokines will be assess from baseline before prophylactic Ikervis, 3 to 5 weeks from baseline (Pre-HSCT), and 3, 6, and 12 months post-HSCT after prophylactic Ikervis.	Baseline, 3 to 5 weeks from baseline (Pre-HSCT), 3 months, 6 months and 1 year post-HSCT follow up
To assess change of conjunctival impression cytology 3 to 5 weeks after prophylactic Ikervis with 12 months post Haematopoietic Stem Cell Transplant.	Conjunctival impression cytology will be performed using EyePrim. The change of conjunctival impression cytology only will be assessed 3 to 5 weeks from baseline (Pre-HSCT) and 12 months post-HSCT after prophylactic Ikervis.	3 to 5 weeks from baseline (Pre-HSCT) and 1 year post-HSCT follow up
To assess change of baseline corneal fluorescein staining score with prophylactic Ikervis after 3 to 5 weeks before Haematopoietic Stem Cell Transplant and 3 months, 6 months and 12 months post Haematopoietic Stem Cell Transplant.	Corneal fluorescein staining (in grade 0-4) will be imaged by Oculus Keratograph K5M. A greater number indicating more intense or greater area of staining. The change of corneal fluorescein staining will be assess from baseline before prophylactic Ikervis, 3 to 5 weeks from baseline (Pre-HSCT), and 3, 6, and 12 months post-HSCT after prophylactic Ikervis.	Baseline, 3 to 5 weeks from baseline (Pre-HSCT), 3 months, 6 months and 1 year post-HSCT follow up
To assess change of baseline Meibomian gland expressibility with prophylactic Ikervis after 3 to 5 weeks before Haematopoietic Stem Cell Transplant and 3 months, 6 months and 12 months post Haematopoietic Stem Cell Transplant.	Meibomian gland expressibility will be assessed using Meibomian gland evaluator. Texture of expressed secretion will be graded as liquid or viscous. The number of expressible glands will be recorded. The change of meibomian gland expressibility will be assess from baseline before prophylactic Ikervis, 3 to 5 weeks from baseline (Pre-HSCT), and 3, 6, and 12 months post-HSCT after prophylactic Ikervis.	Baseline, 3 to 5 weeks from baseline (Pre-HSCT), 3 months, 6 months and 1 year post-HSCT follow up
To assess Quality of Life Questionnaire at 12 months post Haematopoietic Stem Cell Transplant.	Quality of Life (in score 0, 1, 2, 3, 8) will be assessed using Impact of Vision Impairment Profile questionnaire at the end of the prophylactic Ikervis, 12 months post-HSCT. The score in 0 means a lot of the time, 1 means a fair amount of the time, 2 means a little of the time, 3 means not at all, 8 means do not do this for other reasons.	1 year post-HSCT follow up

Collaborators and Investigators

• Sponsor: Singapore Eye Research Institute
• Investigators: Principal Investigator: Li Lim, Senior Consultant

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2019
• Primary Completion (Anticipated): August 22, 2022
• Study Completion (Anticipated): December 30, 2022

Study Registration Dates

• First Submitted: March 9, 2020
• First Submitted That Met QC Criteria: November 14, 2020
• First Posted (Actual): November 19, 2020

Study Record Updates

• Last Update Posted (Actual): November 19, 2020
• Last Update Submitted That Met QC Criteria: November 14, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: R1641/38/2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No