EYS606-CT1 - version 2 2016-09-27
Research type
Research Study
Full title
A Phase I/II, open-label, multicentre, dose escalation study assessing the safety and tolerability of pEYS606 when administered by electrotransfer (ET) in the ciliary muscle of patients with non infectious posterior, intermediate or pan uveitis.
IRAS ID
208162
Contact name
Andrew Dick
Contact email
Sponsor organisation
EYEVENSYS
Eudract number
2015-001391-22
Duration of Study in the UK
1 years, 5 months, 30 days
Research summary
Summary of Research
It's a First In Human study to evaluate safety and tolerability of pEYS606 when administered by electrotransfer (ET) in the ciliary muscle of patients with non-infectious posterior, intermediate or pan uveitis.
pEYS606 is a plasmid DNA formulated as a solution for injection. After injection into the ciliary muscle the plasmid DNA is electro-transferred (ET).
pEYS606 treatment will be evaluated at 3 dose levels. Patients will receive a single administration of pEYS606 in the eligible eye by ET.Summary to Results
General information about the research Title of study:
A Phase I/II, Open-Label, Multicenter, Dose Escalation Study Assessing the Safety and Tolerability of pEYS606 when Administered by Electrotransfer (ET) in the Ciliary Muscle of Patients with Non- Infectious Posterior, Intermediate or Panuveitis Study Sites:
There were 8 sites in the study (5 in France: Hôpital Cochin, Paris; CHU Grenoble, CHU Limoges; CHU Lyon; Rothschild Ophthalmology Foundation and 3 in the United Kingdom [UK]: Moorfields Eye Hospital, London; Bristol Eye Hospital; Maidstone & Tunbridge Wells NHS Trust Maidstone Hospital) that were initiated during the course of the study. Of these, only 4 sites (Hôpital Cochin, Paris and CHU Grenoble in France and Moorfields Eye Hospital and Bristol Eye Hospital in the UK) enrolled and treated participants; a fifth site (CHU-Limoges) provided post-treatment study follow-up visits for one participant enrolled and treated at Hôpital Cochin, Paris.
Reason for the research:
The study was designed to test the safety of a new, non-clinically proven gene treatment for uveitis. The study was designed to determine the most appropriate and the safest dose of the new local treatment (called ‘EYS606’),
EYS606 was composed of an injection of a drug (‘pEYS606’) in the eye using a dedicated medical device (via a process called ‘electrotransfection’) in the treatment of non-infectious uveitis Information from this study may help researchers to better understand the safety and effectiveness of EYS606 and may help improve the treatment of people with uveitis.
This clinical study was conducted in two parts:
- the first part of the study was designed to evaluate the safety of three doses of study medication,
- the second part of the study used the results of the first part to determine and select the safest dose identified to administer to new participants, who were followed after treatment to also evaluate the potential effectiveness of the medication.Main objectives studied:
The primary objective was to assess the safety and tolerability of the study treatment (‘EYS606’) within the first 4 weeks of treatment administration
Other secondary objectives of the study were:
• To obtain additional indicators of long-term safety
• To obtain indicators of clinical activity (response to the study treatment)Who carried out the research?
The research was conducted by the Sponsor, Eyevensys, with its main headquarters in France. Eyevensys funded the research conducted in both France and the UK.
Who participated in the study?
Of the 7 study sites, two sites in France and two sites in the UK enrolled and treated participants; a fifth site (CHU Limoges) provided study follow-up visits for a participant enrolled and treated at Hôpital Cochin, Paris. Only patients with non-infectious uveitis (NIU) who met the specific requirements for study entry were selected to participate in the study.What treatments or interventions did the participants take/receive?
Treated participants received pre-determined doses of the study drug (pEYS606) as an injection in one eye. This was immediately followed by low voltage electrical pulses to the eye, delivered by a medical device specifically made for the study. All study participants were then followed by the study doctor and research team at each site to ensure the participant’s safety and to evaluate the response to the treatment.
In the second part of the study, and in the UK only, some study participants had the option of being retreated if they had initially shown some response to the first treatment, but with the response having lessened over time during the follow-up period.
What medical problems (adverse events) did the participants have?
In study participants, the following adverse events (medical issues) that were considered significant (related to the eye (“ocular”) and/or the study treatment, and/or were considered to be serious and/or were specific adverse events defined by the study plan (or protocol)) were reported:
• Serious Medical Problems (Serious Adverse Events, “SAEs”)
o Ocular/Treatment Related: There were no ocular and/or treatment-related adverse events that were considered to be serious (SAEs), which means there were no serious adverse drug reactions (SADRs) or serious adverse device effects (SADEs), reported for the study
o Other: Two serious adverse events (SAEs), one of cellulitis (an infection of the deeper layers of skin and the underlying tissue) and one of malignant lung neoplasm (lung cancer), were each reported for a study participant, but both cases were judged by the study doctor as unrelated to the study medication (pEYS606) and/or to the treatment device.
• Non-serious Ocular Adverse Events (“AEs”)
o Eight participants experienced adverse events (AEs) of reduced visual acuity, with 9 of these events reported early in the study (shortly after treatment) and 4 reported later in the study follow-up period. Of the 13 events, 12 were transient (temporary), while the outcome of the 13th event was unknown because the participant was unreachable shortly after receiving the study treatment (due to lung cancer). Depending on the severity of the loss, many of these events were also reported as AESI’s (or adverse events of special interest, which were defined by the study protocol (study plan)). (See below.)
o Other post-treatment events: At most visits and throughout the various cohorts (the various dosing groups), the majority of participants reported some eye events as absent or mild. Approximately 60% of participants reported experiencing some eye events as “severe” at least once (across symptoms and visits) after study treatment, with the most frequent symptom categories being: blurred vision, lacrimation (excessive tearing), foreign body sensation, and photophobia (light sensitivity).
• Adverse Events of Special Interest
Seven adverse events of special interest (AESIs, specific adverse events defined by the study protocol (study plan)) in study eyes were recorded in this study:
o One participant experienced an AESI at 1 hour after the procedure (with a 28-letter loss from the initial pre-treatment visual acuity), which resolved at 4 hours after the procedure with a 25-letter improvement. The Sponsor assessed this AESI, which lasted for 3 hours, as likely related to a subconjunctival hemorrhage (a bleed underneath the conjunctiva- the transparent layer which lies over the white of the eye) that the patient was experiencing at the same time.
o Two participants each experienced an AESI at 1 hour after the treatment (one had a 42-letter loss from the initial pre-treatment visual acuity assessment) that resolved at 3 hours after the procedure with a 30-letter improvement; the other had a 33-letter loss at 1 hour after treatment that resolved at 3 hours after the procedure, with a 31-letter improvement). The Sponsor assessed both AESIs, which lasted for 2 hours, as likely related to the preventative ointment that was administered to the eye after the procedure.
o One participant experienced an AESI at 1 hour after treatment (with a 42-letter loss from the initial pre-treatment visual acuity assessment), which returned to the initial pre-treatment value by Visit3/Week 1. The Sponsor assessed this AESI as likely related to the combination of the use of preventative ointment after the procedure and the presence of a subconjunctival hemorrhage (bleeding under the conjunctiva of the eye.)
o One participant experienced 2 AESIs (with a 43-letter decline in visual acuity 84 days after the procedure and a 39-letter decline in visual acuity 333 days after the procedure). The 43-letter loss was assessed by the study doctor as possibly related to the study drug and not related to the medical device. However, after review of the participant’s data, the Sponsor assessed both the 43-letter AESI and the 39-letter AESI as likely related to the participant’s ongoing idiopathic panuveitis (uveitis in both the front and the back of the eye that was of unknown cause).
o One participant experienced one pre-treatment AESI (a 21-letter decline in visual acuity) between the screening visit (Visit 0) and the visual acuity assessments made before the study treatment at the baseline visit (Visit 1 Day 1). Because this AESI occurred prior to any study treatment procedure, the study doctor did not classify this decline in visual acuity as an AE. However, after review of the participant’s data, the Sponsor assessed this as an AESI that was likely related to a worsening of uveitis made apparent by worsening of the macular oedema (swelling in part of the retina (the light-sensitive layer of tissue at the back of the eye)) which was accompanied by decreased visual acuity.
• Electrocardiogram (ECG) results: All ECG results (a simple test that can be used to check heart rhythm and electrical activity) were normal, with the exception of 3 instances: one ECG was assessed by the study doctor as abnormal but not clinically significant and 2 were assessed by the study doctor as clinically significant and unrelated to both the study drug and the device, with one associated with an AE (ventricular dysfunction (heart failure)) and one related to the participant’s medical history of aortic valve stenosis (a narrowing of the aortic valve).
• Electroretinogram (ERG) results: For the ERG (an eye test that aims to discover how well the retina at the back of the eye is working), all but 2 participants had abnormal results at both the screening (Day 0, pre-treatment) visit and at Visit 9/Week 24. One participant had normal ERGs at both visits, and another had an abnormal ERG at screening (Day 0, pre-treatment) and a normal ERG at Visit 9/Week 24. The presence of abnormal ERGs at screening for nearly all participants suggests that these participants already had retinal damage due to the presence of chronic posterior uveitis (persistent uveitis in the back of the eye).
• Post-procedure Pain: Pain recorded by the participants after the study treatment did not exceed a score of 2 (‘Hurts Little Bit’) in most participants at the treatment visit (Visit 1/Day 1) (at 3 or 4 hours after the procedure) and at Visit 2/Day 2. Also, at Visit 2/Day 2, the majority of participants had their pain rating return to the baseline (initial pre-treatment) value (a score of 0 (‘No Hurt’)). No participants experienced a pain score >4 (‘Hurts Little More’) at Visit 3/Week 1 or beyond. Three participants experienced a pain score >5 (6: ‘Hurts Even More’, 8: ‘Hurts Whole Lot’, 10: ‘Hurts Worst’) reported between the baseline (initial pre-treatment) assessment and Visit 5/Week 4. For those who did experience a pain score >5, pain ratings returned to the baseline (initial pre-treatment) value by Visit 2/Day 2 for 2 participants and by Visit 4/Week 2 for one participant.What were the results of the study?
Clinical activity (treatment response) results:
• Four of 7 participants who could be evaluated for a treatment response (57.1%) showed a response with the study treatment (EYS606).
• This treatment response was maintained at Visit 7/Week 24 in 2 of the 4 participants.
• The one participant who was retreated recovered (improved by) 10 letters of the visual acuity assessment following retreatment and this vision was maintained through the end of the study (Visit 13/Week 48).
• One additional participant showed a late treatment response (at Visit 7/Week 12 through the End of the Study Visit). Despite the participant receiving topical alternate therapy between Visit 5/Wek 4 and Visit 6/Week 8, in the opinion of the Sponsor, this late treatment response was likely due to EYS606 rather than the topical alternate therapy, which has a short period of effect.
• No participants showed worsening of vision with the EYS606 treatment.Conclusions:
In this EYS606-CT1 study, 15 participants across 5 investigational sites in France and the UK were enrolled, treated, and followed. Nine participants were enrolled and treated in Part 1 of the study, and 6 participants were enrolled and treated in Part 2 of the research trial (One participant in Part 2 received the study drug injection but the necessary electrical pulse sequence with the study device was not performed.). One participant in Part 1 did not complete the study due to being unreachable after a lung cancer diagnosis, and 2 participants in Part 2 were discontinued from the study per the study doctor’s decision (one after Visit 7/Week 12 and one after Visit 10/Week 30).Where can I learn more about this study?
To learn more about this study, please visit the Sponsor’s website: https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbV-2FOUkfV2qsa1Wm55VRvTgI-3Dxeay_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YKBQ8hK5pJUSA-2FvC5CUBxpFv74-2B5owpjfBaqs5-2FPrTYtjB3-2F8Dks2zzjUR-2FTk-2FYzhchRqF8ZVjtXaplcvlvOKAEQJPXJ35IAN2LyXPofVfgE-2BK2fj6Znr1xiTtKaSe3Kuia74vmIuRDsK3M2fXEGT6-2FgBnvOk6aMWbcHQ7r3j2rXw-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cbbfdfeff9a594e02cf9b08dad1808352%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638052647131609749%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=yeScwfh3X3WlTMEFsCk6SDwNFL1yBylB20O2pWKQc3M%3D&reserved=0REC name
South Central - Oxford A Research Ethics Committee
REC reference
16/SC/0526
Date of REC Opinion
23 May 2017
REC opinion
Further Information Favourable Opinion