Keratoconjunctivitis, AtopicPhase 1/2NCT04037891
Topical rVA576 for Treatment of Atopic Keratoconjunctivitis
A Phase 1/2 study testing rVA576 in people with Keratoconjunctivitis, Atopic and Keratoconjunctivitis, Vernal, run by AKARI Therapeutics at 9 sites in 2 countries.
Trial summary
Topical rVA576 for treatment of atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC),and severe allergic conjunctivitis (seasonal (SAC) or perennial (PAC)): a randomised placebo-controlled double masked parallel trial (TRACKER) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Keratoconjunctivitis, Atopic, Keratoconjunctivitis, Vernal, Conjunctivitis, Allergic
- What is being tested?
- rVA576
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 4 Mar 2019to 30 Apr 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18 and above
- Diagnosis of moderate to severe AKC, VKC, or severe allergic conjunctivitis (seasonal or perennial). Defined as:
- AKC, VKC - a composite symptom/sign score from one eye of ≥ 18 out of 33
- Severe allergic conjunctivitis (SAC or PAC) - a composite symptom/sign score from one eye of ≥ 15 out of 27
- Will have had received some topical therapy during the last 3 months without improvement but will not currently be receiving systemic immunotherapy. Topical therapy may be topical calcineurin inhibitors, antihistamines or corticosteroids alone or in combination. Lubricants or artificial tears will not a count as topical therapy for these purposes.
- Will have had at least 7 days without topical ocular corticosteroids prior to entry
Show all 9Show fewer
- Willing to give informed consent
- Willing to use highly effective contraceptive precautions for the duration of the study and for 90 days after the last dose of IMP
- Willing to avoid prohibited medications for duration of study (see list of prohibited medications)
Who cannot join
- Eye surface disease other than AKC, VKC or severe allergic conjunctivitis (SAC or PAC)
- 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
Show all 23Show fewer
- 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
- Uncontrolled glaucoma (increase in dose of glaucoma medication or surgical intervention for glaucoma within 3 months prior to entry)
- Pregnancy (females)
- Breast feeding (females)
- Known allergy to ticks or severe reaction to arthropod venom (e.g. bee or wasp venom)
- Use of topical ocular steroids within 7 days of the Screening visit
- Failure to satisfy the PI of suitability to participate for any other reason
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
United Kingdom7 sites
Bristol Eye Hospital
Bristol
Addenbrookes Hospital
Cambridge
St James's University Hospital
Leeds
Royal Liverpool University Hospital
Liverpool
Moorfields Eye Hospital NHS Foundation Trust
London, EC1V 2PD
Royal Victoria Infirmary
Newcastle upon Tyne
University Hospital NHS Foundation Trust
Southend-on-Sea
Spain2 sites
Hospital Clinic de Barcelona
Barcelona
Instituto Universitario de Oftalmobiología Aplicada
Valladolid
About this study
Official title: Topical rVA576 for Treatment of Atopic Keratoconjunctivitis: a Randomised Placebo-controlled Double Masked Parallel Trial (TRACKER)
Topical rVA576 for treatment of atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC),and severe allergic conjunctivitis (seasonal (SAC) or perennial (PAC)): a randomised placebo-controlled double masked parallel trial (TRACKER)
Read the 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).
- Being tested
- rVA576, Placebo
- Medical subject headings
- Keratoconjunctivitis, Conjunctivitis, Allergic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rVA576Drug
Also called Nomacopan
Part 1: The first 3 patients selected for the study will be treated with the active drug in open-label.
PlaceboOther
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.
rVA576Drug
Also called Nomacopan
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.
| Study group | Role | What they receive |
|---|---|---|
| rVA576 - Open-label period | Experimental | 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 Receives: Drug: rVA576 |
| Placebo - Double-blind period | Placebo comparator | 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. Receives: Other: Placebo |
| rVA576 - Double-blind period | Experimental | 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. Receives: Drug: rVA576 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Ocular TEAE
Incidence of ocular treatment-emergent adverse events (TEAE) during the treatment period which have occurred during the 56 days following randomisation.
Measured: 56 days
Secondary outcomes (5)
Post-instillation Comfort
Graded on patient diary cards at the intervals Day 1-14, 15-28, 29-42 and 43-56.
Eye comfort scoring:
0 - Perfectly comfortable
- - Slight discomfort. 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 0.5 minute or longer but improves without treatment.
- - Severe discomfort. Burning, itching or stinging last for at least 0.5 minute and requires washing the eyes to relieve it.
- - Unbearable burning itching or stinging. So severe that you cannot continue treatment.
The 14 day average score for each interval have been calculated for each patient (possible range of 0 to 40). Classifications were assigned using the average total score at each two week period as follows:
< 10 = Comfortable/Acceptable, 10 - 19 = Moderately Uncomfortable, 20 - 29 = Very Uncomfortable, >= 30 = Severely/Unacceptably Uncomfortable.
Measured: Day 1 to 56
Visual Acuity
Visual acuity for the worst eye over time by Early Treatment Diabetic Retinopathy Study (ETDRS) charts comparison from Day 1 to Day 56 In ETDRS charts, zero indicates standard vision, positive values indicates poor vision, and negative values indicates good vision.
Measured: Day 1 to 56
Clinical Scores
Change from Day 1 in composite clinical scores at Day 14, 28, 42 and 56, for the eye judged as worst affected at each visit. Score calculated from symptom and sign sub-components.
AKC/VKC: symptom sub-component consisted of itch, tearing, discomfort, discharge, and photophobia, and the sign component consisted of bulbar conjunctival hyperaemia, tarsal conjunctival papillary hypertrophy, punctate keratitis, neovascularization of cornea, cicatrizing conjunctivitis, blepharitis.
SAC/PAC: symptom sub-component consisted itch, tearing, discomfort, and photophobia, and the sign sub-component consisted of upper tarsal conjunctival hyperaemia, upper bulbar conjunctival hyperaemia, chemosis, upper tarsal conjunctival papillae, blepharitis.
For each sign/symptom a score of 0 - 3 is awarded (0=absence of a sign/symptom; an increase in score indicates increase in severity). These scores are summed at the end of the exam to give the composite score. Range:0 to 33 (AKC/VKC) or 27 (SAC/PAC).
Measured: Day 1 to 56
MMP-9 Positive
Percentage of patients with Matrix metalloprotease 9 (MMP-9) positive levels at Days 1, 28, and 56.
MMP-9 is a is a nonspecific inflammatory marker. Detection was made using the Inflammadry® device. This device gives a binary (positive/negative) result.
Measured: Day 1 to 56
Tear Film Break up Time
Change from Day 1 in Tear film break up time (TBUT) at Day 14, 28, 42 and 56. TBUT data was available for one eye only. Tear breakup time (TBUT) is a clinical test used to assess for evaporative dry eye disease. To measure TBUT, fluorescein is instilled into the patient's tear film and the patient is asked not to blink while the tear film is observed under a broad beam of cobalt blue illumination. The TBUT is recorded as the number of seconds that elapse between the last blink and the appearance of the first dry spot in the tear film. A TBUT under 10 seconds is considered abnormal.
Measured: Change from Day 1 at Day 14, 28, 42 and 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2019
- Study start4 Mar 2019
- Primary completion30 Apr 2020
- Study completion30 Apr 2020
Why it 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Keratoconjunctivitis, AtopicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- AKARI Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sajjad Ahmad, Principal investigator, Moorfields Eye Hospital NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04037891
- Sponsor's protocol ID
- AK701
- Status last verified
- Jul 2024
- First submitted
- 13 Feb 2019
- Last updated
- 10 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Topical rVA576 for Treatment of Atopic Keratoconjunctivitis: a Randomised Placebo-controlled Double Masked Parallel Trial (TRACKER)
- ClinicalTrials.gov ID
- NCT04037891
- Acronym / sponsor ID
- AK701
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason 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.
- Enrolment
- 12 participants (actual)
- Lead sponsor
- AKARI TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 4 Mar 2019 (actual)
- Primary completion
- 30 Apr 2020 (actual)
- Study completion
- 30 Apr 2020 (actual)
- First posted
- 30 Jul 2019 (actual)
- Results
- Posted 27 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Topical rVA576 for treatment of atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC),and severe allergic conjunctivitis (seasonal (SAC) or perennial (PAC)): 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| rVA576 - Open-label period | Experimental | Drug: rVA576Part 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 |
| Placebo - Double-blind period | Placebo comparator | Other: PlaceboPart 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. |
| rVA576 - Double-blind period | Experimental | Drug: rVA576Part 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Aged 18 and above
- Diagnosis of moderate to severe AKC, VKC, or severe allergic conjunctivitis (seasonal or perennial). Defined as:
- Will have had received some topical therapy during the last 3 months without improvement but will not currently be receiving systemic immunotherapy. Topical therapy may be topical calcineurin inhibitors, antihistamines or corticosteroids alone or in combination. Lubricants or artificial tears will not a count as topical therapy for these purposes.
- Will have had at least 7 days without topical ocular corticosteroids prior to entry
- Willing to give informed consent
Key exclusion criteria (23 listed)
- Eye surface disease other than AKC, VKC or severe allergic conjunctivitis (SAC or PAC)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rVA576Also: NomacopanPart 1: The first 3 patients selected for the study will be treated with the active drug in open-label. | Drug | rVA576 - Open-label period |
| PlaceboPart 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. | Other | Placebo - Double-blind period |
| rVA576Also: NomacopanPart 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. | Drug | rVA576 - Double-blind period |
Primary outcome
Incidence of Ocular TEAE
Time frame: 56 days
Incidence of ocular treatment-emergent adverse events (TEAE) during the treatment period which have occurred during the 56 days following randomisation.
5 secondary outcomes
Post-instillation Comfort
Time frame: Day 1 to 56
Visual Acuity
Time frame: Day 1 to 56
Clinical Scores
Time frame: Day 1 to 56
MMP-9 Positive
Time frame: Day 1 to 56
Tear Film Break up Time
Time frame: Change from Day 1 at Day 14, 28, 42 and 56
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Keratoconjunctivitis, Atopic
RecruitingPhase 3
An Efficacy and Safety Study of DFL24498 in the Treatment of AKC
Atopic Keratoconjunctivitis
Active, not recruitingObservational study
Ocular Comorbidity in Atopic Dermatitis
Atopic Keratoconjunctivitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sajjad Ahmad principal investigator
Moorfields Eye Hospital NHS Foundation Trust
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing rVA576 in people with Keratoconjunctivitis, Atopic and Keratoconjunctivitis, Vernal, run by AKARI Therapeutics at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United Kingdom, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Ocular TEAE (time frame: 56 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2025.