RAFT - Clinical Trial of RAFT for Aniridia Related Keratopathy (RAFT)

RAFT - First in Human Phase I/II Clinical Trial of RAFT for Aniridia Related Keratopathy

The RAFT trial is a first in human trial of a novel cellular therapy called RAFT-OS (Real Architecture for 3D Tissues Ocular Surface) developed and manufactured by Cells for Sight Stem Cell Therapy Research Unit at UCL institute of Ophthalmology.

The aim of this seamless phase I/II single-dose, single-arm trial is to investigate if RAFT-OS is a safe and effective alternative treatment for patients with aniridia related keratopathy (ARK) in 21 patients.

ARK is a complication of aniridia, which is a genetic eye condition present from birth.

RAFT-OS is an artificial tissue, populated with limbal epithelial cells and stromal cells. The source of the adult limbal and stromal cells is from donated human corneas from the NHS blood and Transplant, Tissue and Eye services in Liverpool.

Following a Screening visit, participants will commence 10-weeks of immune suppression therapy to prepare for the transplantation of RAFT-OS.

The RAFT-OS will be transplanted into the participants worst affected eye. Following surgery, each participant will be assessed at days 1, 7, 14, 21, and 1-month for major or intermediate safety events. Participants will continue to be followed up to 12 months after transplantation and will be required to stay on the immune suppression therapy for the duration of the trial.

The trial is conducted at Moorfields Eye Hospital NHS Foundation Trust (MEH), London in the United Kingdom (UK). MEH is a leading provider of eye health services in the UK and is a world-class centre of excellence for ophthalmic research and education.

All trial medical assessments and procedures will be performed in an appropriate clinical setting by suitability qualified staff.

Study Overview

• Status: Completed
• Conditions: Aniridia
• Intervention / Treatment: Other: RAFT-OS

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, EC1V 2PD
    • Moorfields Eye Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Confirmed diagnosis of congenital aniridia
2. Confirmed diagnosis of advanced aniridia related keratopathy with corneal surface conjunctivalisation, vascularisation and increasing opacity with worsening vision loss, glare & ocular surface pain
3. Patients aged 18 years and over
4. Participants must use acceptable contraception from enrolment up to 6 weeks for female participants and 90 days for male participants, after stopping immunosuppression therapy
5. Negative viral screen for, HIV, syphilis, hepatitis B & C and Human T-cell Leukaemia Virus (HTLV)
6. Negative urine pregnancy test.

Exclusion Criteria:

1. Poor tear production, as assessed by a Schirmer's test type 1
2. Lid malposition (entropion, ectropion, fornix shortening, symblepharon)
3. Current corneal infection
4. Uncontrolled glaucoma (defined as uncontrolled eye pressure, changes to medication, recent surgery in the last 3 months or being considered for surgical treatment)
5. Must not be NPL (no light perception) in one or both eyes
6. Patients who refuse to consent to the site informing their GP of their participation
7. Patients who lack capacity to give full informed consent to participate
8. Pregnant or lactating women
9. Patients with known contraindications to any of the following non-investigational medicinal products; mycophenolate, prednisolone, omeprazole, doxycycline, dexamethasone & moxifloxacin or excipients according to the relevant SmPCs
10. Patients who are participating in any concurrent trial involving an investigational medical product, device or surgical intervention within the last 12 months
11. Known albumin or egg allergy
12. Known penicillin allergy
13. Known hydrocortisone allergy
14. Inability to lie flat for surgical procedure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: RAFT-OS; Single-arm trial is to investigate if RAFT-OS ((Real Architecture for 3D Tissues Ocular Surface) is a safe and effective alternative treatment for patients with aniridia related keratopathy (ARK) in 21 patients. The RAFT-OS will be transplanted into the participants worst affected eye. Following surgery, each participant will be assessed at days 1, 7, 14, 21, and 1-month for major or intermediate safety events. Participants will continue to be followed up to 12 months after transplantation and will be required to stay on the immune suppression therapy for the duration of the trial.

Other: RAFT-OS; RAFT-OS (Real Architecture for 3D Tissues Ocular Surface) is an artificial tissue, populated with limbal epithelial cells and stromal cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary safety outcome defined as the number of adverse events related to the intervention	defined as either major adverse event (non-ocular SUSAR; corneal melting; death) or any intermediate adverse event (persisting epithelial defect; persisting ocular inflammation; loss of corneal clarity; ocular SAEs related to the RAFT-OS and not surgery alone, conjunctival or lid swelling considered related to the ATIMP (RAFT-OS) and not surgery alone).	12 months
primary efficacy outcome defined as Improvement in the corneal surface at 3months post intervention.	Efficacy will be based on corneal surface normalisation (i.e., persistence of normal corneal epithelium and absence of vascularisation, epithelial defect and conjunctivalisation) at 3 months post-RAFT-OS transplantation using a validated ocular surface scoring system	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in visual acuity	1. Visual improvement assessed by distance EDTRS visual acuity (refractive best corrected) at 3 & 12 months post RAFT-OS transplantation.	3 & 12 months post RAFT transplantation
changes in quality of life scores	as assessed by NEI-VFQ-25 patient questionnaire	at 3 & 12 months post RAFT transplantation
Changes in quality of Life scores	RAND 36-Item Health Survey.	3 &12 months post RAFT transplantation.

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: Medical Research Council; Moorfields Eye Hospital NHS Foundation Trust
• Investigators: Principal Investigator: Sajjad Ahmad, Moorfields Eye Hospital, London; Study Chair: Julie Daniels, University College, London

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2021
• Primary Completion (Actual): April 17, 2025
• Study Completion (Actual): April 17, 2025

Study Registration Dates

• First Submitted: May 19, 2021
• First Submitted That Met QC Criteria: September 9, 2021
• First Posted (Actual): September 16, 2021

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 25, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Eye Diseases; Eye Diseases, Hereditary; Congenital Abnormalities; Uveal Diseases; Eye Abnormalities; Iris Diseases; Aniridia
• Other Study ID Numbers: CTU/2017/307

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