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Topical rVA576 for Treatment of Atopic Keratoconjunctivitis

Primary Purpose

Atopic Keratoconjunctivitis (AKC)

Status
Terminated
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
rVA576
Placebo
Sponsored by
AKARI Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atopic Keratoconjunctivitis (AKC)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Aged 18 and above
  2. Diagnosis of moderate to severe AKC with a composite symptom/sign score from one eye of ≥ 22 out of 33 (see Clinical Scoring 17.1)
  3. Will have had maximal topical therapy for at least 3 months without improvement but will not currently be receiving systemic immunotherapy.
  4. History of atopy other than ocular (dermatitis, asthma, hay fever)
  5. Willing to give informed consent
  6. Willing to use adequate contraceptive precautions for the duration of the study and for 90 days thereafter
  7. Willing to avoid prohibited medications for the duration of the study

Exclusion Criteria:

  1. Eye surface disease other than AKC
  2. Contact lens use during the study
  3. Complete or partial tarsorrhaphy. If such a procedure becomes necessary during the course of the trial patients may remain in the trial providing that at least 50% of the eye surface remains visible to slit lamp examination
  4. Ankyloblepharon of any degree at entry to the trial
  5. Known or suspected ocular malignancy
  6. Active ocular infection at entry to the trial. Patients with eye surface bacterial, viral, fungal or protozoal infection may enter the trial after elimination of the infection as confirmed by eye swabs
  7. Known or suspected uveitis
  8. Participation in any other clinical trial within 1 month of enrolment

  9. Use of any of the following prohibited medications:

    • Eculizumab
    • Any other investigational complement inhibitor whether systemic or topical (e.g. RA101495)
    • Montelukast
    • Zafirlukast
    • Pranlukast
    • Zileuton
    • Hypericum perforatum (St John's wort)
  10. Corneal perforation
  11. Glaucoma
  12. Pregnancy (females)
  13. Breast feeding (females)
  14. Known allergy to ticks or severe reaction to arthropod venom (e.g. bee or wasp venom)
  15. Failure to satisfy the PI of suitability to participate for any other reason

Sites / Locations

  • Moorfields Eye Hospital NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

rVA576

Placebo

Arm Description

Part 1: The first 3 patients selected for the study will be treated with the active drug in an open-label manner at intervals of 1 week and will have weekly clinic visits until Day 14, after which the visit will be every two weeks. When the first 3 patients have completed two weeks of treatment and the safety and tolerability data has been reviewed by the PI and an independent clinician, provided the data is favourable the randomisation process will begin (Part 2). The first 3 patients will continue treatment for a total of 8 weeks and will be assessed throughout the trial by the Principal Investigator according to the Schedule of Events Part 2: Sixteen patients will be randomised 1:1. between active and placebo and patients allocated to either group will receive the appropriate product throughout the trial.

Part 2: Sixteen patients will be randomised 1:1. between active and placebo and patients allocated to either group will receive the appropriate product throughout the trial.

Outcomes

Primary Outcome Measures

Safety Parameter
Incidence of ocular treatment emergent adverse events during the treatment period which have occurred during the 56 days following randomisation.

Secondary Outcome Measures

Post-instillation comfort
Post-instillation comfort, as graded on patient diary cards at the following intervals Days 1-14, Day 15-28, Day 29-42 and Day 43-56. Eye comfort scoring (0-5): 0 Perfectly comfortable Slight discomfort. Aware of some burning, itching or stinging for up to half a minute after using the eye drop, solution but the discomfort improves without treatment. Moderate discomfort. Burning, itching or stinging lasts for half a minute or longer but improves without treatment. Severe discomfort. Burning, itching or stinging last for at least half a minute and requires washing the eyes to relieve it. Unbearable burning itching or stinging. So severe that you cannot continue treatment.
Visual acuity
Visual acuity by Early Treatment Diabetic Retinopathy Study (ETDRS) charts comparison from Day 1 to Day 56
Clinical scores
Change from Day 1 in composite clinical scores at Day 14, 28, 42 and 56 Outcome measure information describes more than one measure The primary efficacy endpoint is a composite clinical score made up of 5 symptoms and 6 signs as follows: Symptoms Itching Tearing Discomfort (burning, stinging or foreign body sensation) Discharge Photophobia Signs Bulbar conjunctival hyperaemia Tarsal conjunctival papillary hypertrophy Punctate keratitis Neovascularisation of cornea Cicatrising conjunctivitis Blepharitis
MMP-9 positive
Percentage of patients with MMP-9 positive levels at Days 1, 28, and 56

Full Information

First Posted
February 13, 2019
Last Updated
March 16, 2021
Sponsor
AKARI Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT04037891
Brief Title
Topical rVA576 for Treatment of Atopic Keratoconjunctivitis
Official Title
Topical rVA576 for Treatment of Atopic Keratoconjunctivitis: a Randomised Placebo-controlled Double Masked Parallel Trial (TRACKER)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Terminated
Why Stopped
The trial has terminated early due to the disruptions caused by the ongoing COVID-19 pandemic. The decision was not related to any efficacy, safety or clinical concerns regarding rVA576/Coversin.
Study Start Date
February 20, 2019 (Actual)
Primary Completion Date
December 15, 2020 (Actual)
Study Completion Date
December 15, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AKARI Therapeutics

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
Topical rVA576 for treatment of atopic keratoconjunctivitis: a randomised placebo-controlled double masked parallel trial (TRACKER)
Detailed Description
Recombinant rVA576 is a small protein (16.7kDa) which has two independent actions. It inhibits the activation and cleavage of complement C5 and it binds and inactivates leukotriene B4 (LTB4). It acts on the complement system by preventing the cleavage of C5 by C5 convertase into C5a and C5b and so is effective in inhibiting terminal complement activity irrespective of the activating pathway. Atopic keratoconjunctivitis (AKC) is a type of allergic conjunctivitis which involves mast cell activation due to the predominance of inflammatory mediators such as eosinophils and Th2-generated cytokines (Mishra et al. 2011). Recombinant rVA576 eye drops solution is the investigational medicinal product. It is intended for ophthalmic use by topical administration to the eye. Recombinant rVA576 is a compact small protein molecule with a lipocalin-like structure consisting of alpha helices and a beta barrel. There is a surface-active site which binds to the complement C5 molecule with a high affinity (KD 1.85 x 10-8 M) and an internalised active site which binds the small eicosinoid molecule leukotriene B4 (Hepburn et al. 2007).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atopic Keratoconjunctivitis (AKC)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Randomised, double-masked, placebo-controlled parallel group comparison with open-label sentinel group.
Allocation
Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
rVA576
Arm Type
Experimental
Arm Description
Part 1: The first 3 patients selected for the study will be treated with the active drug in an open-label manner at intervals of 1 week and will have weekly clinic visits until Day 14, after which the visit will be every two weeks. When the first 3 patients have completed two weeks of treatment and the safety and tolerability data has been reviewed by the PI and an independent clinician, provided the data is favourable the randomisation process will begin (Part 2). The first 3 patients will continue treatment for a total of 8 weeks and will be assessed throughout the trial by the Principal Investigator according to the Schedule of Events Part 2: Sixteen patients will be randomised 1:1. between active and placebo and patients allocated to either group will receive the appropriate product throughout the trial.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Part 2: Sixteen patients will be randomised 1:1. between active and placebo and patients allocated to either group will receive the appropriate product throughout the trial.
Intervention Type
Drug
Intervention Name(s)
rVA576
Other Intervention Name(s)
Coversin
Intervention Description
19 Patients with moderate to severe AKC. the study includes two parts: Part 1: The first 3 patients selected for the study will be treated with the active drug in open-label. Part 2: Sixteen patients will be randomised 1:1. between active and placebo and patients allocated to either group will receive the appropriate product throughout the trial.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Part 2: Sixteen patients will be randomised 1:1. between active and placebo and patients allocated to either group will receive the appropriate product throughout the trial.
Primary Outcome Measure Information:
Title
Safety Parameter
Description
Incidence of ocular treatment emergent adverse events during the treatment period which have occurred during the 56 days following randomisation.
Time Frame
56 days
Secondary Outcome Measure Information:
Title
Post-instillation comfort
Description
Post-instillation comfort, as graded on patient diary cards at the following intervals Days 1-14, Day 15-28, Day 29-42 and Day 43-56. Eye comfort scoring (0-5): 0 Perfectly comfortable Slight discomfort. Aware of some burning, itching or stinging for up to half a minute after using the eye drop, solution but the discomfort improves without treatment. Moderate discomfort. Burning, itching or stinging lasts for half a minute or longer but improves without treatment. Severe discomfort. Burning, itching or stinging last for at least half a minute and requires washing the eyes to relieve it. Unbearable burning itching or stinging. So severe that you cannot continue treatment.
Time Frame
Day1 to 56
Title
Visual acuity
Description
Visual acuity by Early Treatment Diabetic Retinopathy Study (ETDRS) charts comparison from Day 1 to Day 56
Time Frame
Day1 to 56
Title
Clinical scores
Description
Change from Day 1 in composite clinical scores at Day 14, 28, 42 and 56 Outcome measure information describes more than one measure The primary efficacy endpoint is a composite clinical score made up of 5 symptoms and 6 signs as follows: Symptoms Itching Tearing Discomfort (burning, stinging or foreign body sensation) Discharge Photophobia Signs Bulbar conjunctival hyperaemia Tarsal conjunctival papillary hypertrophy Punctate keratitis Neovascularisation of cornea Cicatrising conjunctivitis Blepharitis
Time Frame
Day1 to 56
Title
MMP-9 positive
Description
Percentage of patients with MMP-9 positive levels at Days 1, 28, and 56
Time Frame
Day1 to 56

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Aged 18 and above Diagnosis of moderate to severe AKC with a composite symptom/sign score from one eye of ≥ 22 out of 33 (see Clinical Scoring 17.1) Will have had maximal topical therapy for at least 3 months without improvement but will not currently be receiving systemic immunotherapy. History of atopy other than ocular (dermatitis, asthma, hay fever) Willing to give informed consent Willing to use adequate contraceptive precautions for the duration of the study and for 90 days thereafter Willing to avoid prohibited medications for the duration of the study Exclusion Criteria: Eye surface disease other than AKC Contact lens use during the study Complete or partial tarsorrhaphy. If such a procedure becomes necessary during the course of the trial patients may remain in the trial providing that at least 50% of the eye surface remains visible to slit lamp examination Ankyloblepharon of any degree at entry to the trial Known or suspected ocular malignancy Active ocular infection at entry to the trial. Patients with eye surface bacterial, viral, fungal or protozoal infection may enter the trial after elimination of the infection as confirmed by eye swabs Known or suspected uveitis Participation in any other clinical trial within 1 month of enrolment Use of any of the following prohibited medications: Eculizumab Any other investigational complement inhibitor whether systemic or topical (e.g. RA101495) Montelukast Zafirlukast Pranlukast Zileuton Hypericum perforatum (St John's wort) Corneal perforation Glaucoma Pregnancy (females) Breast feeding (females) Known allergy to ticks or severe reaction to arthropod venom (e.g. bee or wasp venom) Failure to satisfy the PI of suitability to participate for any other reason
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sajjad Ahmad
Organizational Affiliation
Moorfields Eye Hospital NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Moorfields Eye Hospital NHS Foundation Trust
City
London
ZIP/Postal Code
EC1V 2PD
Country
United Kingdom

12. IPD Sharing Statement

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Topical rVA576 for Treatment of Atopic Keratoconjunctivitis

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