RAFT - Clinical Trial of RAFT for Aniridia Related Keratopathy (RAFT)
Primary Purpose
Aniridia
Status
Recruiting
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
RAFT-OS
Sponsored by
About this trial
This is an interventional treatment trial for Aniridia
Eligibility Criteria
Inclusion Criteria:
- Confirmed diagnosis of congenital aniridia
- Confirmed diagnosis of advanced aniridia related keratopathy with corneal surface conjunctivalisation, vascularisation and increasing opacity with worsening vision loss, glare & ocular surface pain
- Patients aged 18 years and over
- Participants must use acceptable contraception from enrolment up to 6 weeks for female participants and 90 days for male participants, after stopping immunosuppression therapy
- Negative viral screen for, HIV, syphilis, hepatitis B & C and Human T-cell Leukaemia Virus (HTLV)
- Negative urine pregnancy test.
Exclusion Criteria:
- Poor tear production, as assessed by a Schirmer's test type 1
- Lid malposition
- Current corneal infection
- Uncontrolled glaucoma (defined as uncontrolled eye pressure, changes to medication, recent surgery in the last 3 months or being considered for surgical treatment)
- Must not be NPL (no light perception) in one or both eyes
- Patients who refuse to consent to the site informing their GP of their participation
- Patients who lack capacity to give full informed consent to participate
- Pregnant or lactating women
- Patients with known contraindications to any of the following non-investigational medicinal products; mycophenolate, prednisolone, omeprazole, doxycycline, dexamethasone & moxifloxacin
- Patients who are participating in any concurrent trial involving an investigational medical product, device or surgical intervention within the last 12 months
- Known albumin or egg allergy
- Known penicillin allergy
- Known hydrocortisone allergy
- Inability to lie flat for surgical procedure.
Sites / Locations
- Moorfields Eye HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
RAFT-OS
Arm Description
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.
Outcomes
Primary Outcome Measures
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).
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
Secondary Outcome Measures
Change in visual acuity
1. Visual improvement assessed by distance EDTRS visual acuity (refractive best corrected) at 3 & 12 months post RAFT-OS transplantation.
changes in quality of life scores
as assessed by NEI-VFQ-25 patient questionnaire
Changes in quality of Life scores
RAND 36-Item Health Survey.
Full Information
NCT ID
NCT05044598
First Posted
May 19, 2021
Last Updated
May 31, 2023
Sponsor
University College, London
Collaborators
Medical Research Council, Moorfields Eye Hospital NHS Foundation Trust
1. Study Identification
Unique Protocol Identification Number
NCT05044598
Brief Title
RAFT - Clinical Trial of RAFT for Aniridia Related Keratopathy
Acronym
RAFT
Official Title
RAFT - First in Human Phase I/II Clinical Trial of RAFT for Aniridia Related Keratopathy
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 28, 2021 (Actual)
Primary Completion Date
February 28, 2025 (Anticipated)
Study Completion Date
May 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London
Collaborators
Medical Research Council, Moorfields Eye Hospital NHS Foundation Trust
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aniridia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
RAFT-OS
Arm Type
Other
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
RAFT-OS
Intervention Description
RAFT-OS (Real Architecture for 3D Tissues Ocular Surface) is an artificial tissue, populated with limbal epithelial cells and stromal cells.
Primary Outcome Measure Information:
Title
Primary safety outcome defined as the number of adverse events related to the intervention
Description
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).
Time Frame
12 months
Title
primary efficacy outcome defined as Improvement in the corneal surface at 3months post intervention.
Description
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
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Change in visual acuity
Description
1. Visual improvement assessed by distance EDTRS visual acuity (refractive best corrected) at 3 & 12 months post RAFT-OS transplantation.
Time Frame
3 & 12 months post RAFT transplantation
Title
changes in quality of life scores
Description
as assessed by NEI-VFQ-25 patient questionnaire
Time Frame
at 3 & 12 months post RAFT transplantation
Title
Changes in quality of Life scores
Description
RAND 36-Item Health Survey.
Time Frame
3 &12 months post RAFT transplantation.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Confirmed diagnosis of congenital aniridia
Confirmed diagnosis of advanced aniridia related keratopathy with corneal surface conjunctivalisation, vascularisation and increasing opacity with worsening vision loss, glare & ocular surface pain
Patients aged 18 years and over
Participants must use acceptable contraception from enrolment up to 6 weeks for female participants and 90 days for male participants, after stopping immunosuppression therapy
Negative viral screen for, HIV, syphilis, hepatitis B & C and Human T-cell Leukaemia Virus (HTLV)
Negative urine pregnancy test.
Exclusion Criteria:
Poor tear production, as assessed by a Schirmer's test type 1
Lid malposition (entropion, ectropion, fornix shortening, symblepharon)
Current corneal infection
Uncontrolled glaucoma (defined as uncontrolled eye pressure, changes to medication, recent surgery in the last 3 months or being considered for surgical treatment)
Must not be NPL (no light perception) in one or both eyes
Patients who refuse to consent to the site informing their GP of their participation
Patients who lack capacity to give full informed consent to participate
Pregnant or lactating women
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
Patients who are participating in any concurrent trial involving an investigational medical product, device or surgical intervention within the last 12 months
Known albumin or egg allergy
Known penicillin allergy
Known hydrocortisone allergy
Inability to lie flat for surgical procedure.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amalia Ndoutoumou
Phone
020 3108 9840
Email
raft@ucl.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Liz Deane
Email
raft@ucl.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sajjad Ahmad
Organizational Affiliation
Moorfields Eye Hospital, London
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Julie Daniels
Organizational Affiliation
University College, London
Official's Role
Study Chair
Facility Information:
Facility Name
Moorfields Eye Hospital
City
London
ZIP/Postal Code
EC1V 2PD
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sajjad Ahmad
Phone
0207 566 2320
Email
sajjad.ahmad3@nhs.net
First Name & Middle Initial & Last Name & Degree
Abigail Kaye
Phone
0207 566 2320
Email
Abigail.kaye2@nhs.net
First Name & Middle Initial & Last Name & Degree
Sajjad Ahmad
First Name & Middle Initial & Last Name & Degree
Julie Daniels
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
RAFT - Clinical Trial of RAFT for Aniridia Related Keratopathy
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