A Phase 1/2 interventional study of rVA576 and Placebo in Keratoconjunctivitis, Atopic, Keratoconjunctivitis, Vernal and Conjunctivitis, Allergic, sponsored by AKARI Therapeutics. Terminated at 9 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-04-10.
Sponsored by AKARI Therapeutics · Phase 1/2, Interventional, and Treatment
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)
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).
27 studies on the registry are indexed under Keratoconjunctivitis; 3 are open to participants now.
This study's enrollment of 12 is below the median of 45 across 19 interventional studies indexed under Keratoconjunctivitis.
Browse Keratoconjunctivitis studies →AKARI Therapeutics is the lead sponsor of 8 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Diagnosis of moderate to severe AKC, VKC, or severe allergic conjunctivitis (seasonal or perennial). Defined as:
Exclusion Criteria:
Use of any of the following prohibited medications:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
Drug: rVA576
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.
Other: Placebo
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.
Drug: rVA576
Part 1: The first 3 patients selected for the study will be treated with the active drug in open-label.
Also known as: 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.
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.
Also known as: Nomacopan
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.
Time frame: 56 days
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 1. - 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. 2. - Moderate discomfort. Burning, itching or stinging lasts for 0.5 minute or longer but improves without treatment. 3. - Severe discomfort. Burning, itching or stinging last for at least 0.5 minute and requires washing the eyes to relieve it. 4. - 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: Change from Day 1 at Day 14, 28, 42 and 56
| Milestone | rVA576, Open-label Period (8 Weeks) | rVA576, Double-blind Period (8 Weeks) | Placebo (8 Weeks) |
|---|---|---|---|
| Started | 3 | 0 | 0 |
| Completed | 2 | 0 | 0 |
| Not completed | 1 | 0 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 | 0 |
| Milestone | rVA576, Open-label Period (8 Weeks) | rVA576, Double-blind Period (8 Weeks) | Placebo (8 Weeks) |
|---|---|---|---|
| Started | 0 | 3 | 6 |
| Completed | 0 | 2 | 6 |
| Not completed | 0 | 1 | 0 |
| Withdrew: Withdrawal by subject | 0 | 1 | 0 |
Incidence of ocular treatment-emergent adverse events (TEAE) during the treatment period which have occurred during the 56 days following randomisation.
| Participants | rVA576, Open-label Period | rVA576, Double-blind Period | Placebo |
|---|---|---|---|
| Incidence of Ocular TEAE | 3 | 2 | 3 |
Graded on patient diary cards at the intervals Day 1-14, 15-28, 29-42 and 43-56. Eye comfort scoring: 0 - Perfectly comfortable 1. - 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. 2. - Moderate discomfort. Burning, itching or stinging lasts for 0.5 minute or longer but improves without treatment. 3. - Severe discomfort. Burning, itching or stinging last for at least 0.5 minute and requires washing the eyes to relieve it. 4. - 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.
| Participants | rVA576, Open-label Period | rVA576, Double-blind Period | Placebo |
|---|---|---|---|
| Day 1 to 14 — Comfortable/Acceptable | 3 | 1 | 4 |
| Day 1 to 14 — Moderately Uncomfortable | 0 | 1 | 2 |
| Days 15 to 28 — Comfortable/Acceptable | 2 | 2 | 5 |
| Days 15 to 28 — Moderately Uncomfortable | 0 | 0 | 1 |
| Days 29 to 42 — Comfortable/Acceptable | 2 | 1 | 4 |
| Days 29 to 42 — Moderately Uncomfortable | 0 | 1 | 2 |
| Days 43 to 56 — Comfortable/Acceptable | 2 | 1 | 5 |
| Days 43 to 56 — Moderately Uncomfortable | 0 | 1 | 1 |
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.
| Number of ETDRS letters | rVA576, Open-label Period | rVA576, Double-blind Period | Placebo |
|---|---|---|---|
| Baseline | 56.7 ± 49.1 | 66.0 ± 19.8 | 82.7 ± 8.778 |
| Day 14 | 59.0 ± 48.5 | 82.0 ± 0 | 82.0 ± 7.18 |
| Day 28 | 84.0 ± 0.0 | 78.0 ± 0 | 79.8 ± 10.68 |
| Day 42 | 85.5 ± 0.7 | 83.0 ± 0 | 79.3 ± 15.33 |
| Day 56 (end of dosing) | 87.0 ± 1.4 | 81.0 ± 0 | 77.0 ± 10.56 |
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).
| score on a scale | rVA576, Open-label Period | rVA576, Double-blind Period | Placebo (AKC/VKC) | Placebo (SAC/PAC) |
|---|---|---|---|---|
| Baseline | 23.2 ± 1.53 | 20.7 ± 2.31 | 21.3 ± 1.26 | 19.5 ± 3.54 |
| Day 14 | 16.0 ± 5.20 | 15.0 ± 1.41 | 14.8 ± 3.5 | 17.5 ± 6.36 |
| Day 28 | 14.5 ± 0.71 | 19.0 ± 7.07 | 15 ± 5.48 | 17.5 ± 7.78 |
| Day 42 | 16.0 ± 7.07 | 16.5 ± 2.12 | 11.8 ± 5.32 | — |
| Day 56 | 10.5 ± 0.71 | 15.0 ± 1.41 | 11.0 ± 7.28 | — |
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.
| Participants | rVA576, Open-label Period | rVA576, Double-blind Period | Placebo |
|---|---|---|---|
| Baseline left eye — Positive | 2 | 2 | 4 |
| Baseline left eye — Negative | 1 | 1 | 2 |
| Baseline right eye — Positive | 2 | 3 | 2 |
| Baseline right eye — Negative | 1 | 0 | 4 |
| Day 28 left eye — Positive | 0 | 2 | 3 |
| Day 28 left eye — Negative | 2 | 0 | 3 |
| Day 28 right eye — Positive | 2 | 2 | 2 |
| Day 28 right eye — Negative | 0 | 0 | 3 |
| Day 56 left eye — Positive | 1 | 1 | 0 |
| Day 56 left eye — Negative | 1 | 1 | 5 |
| Day 56 right eye — Positive | 1 | 2 | 1 |
| Day 56 right eye — Negative | 1 | 0 | 3 |
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.
| seconds | rVA576, Open-label Period | rVA576, Double-blind Period | Placebo |
|---|---|---|---|
| Baseline | 5.0 ± 5.57 | 3.0 ± 1.00 | 3.5 ± 1.05 |
| Day 14 | 6.0 ± 3.61 | 2.5 ± 0.71 | 3.7 ± 2.25 |
| Day 28 | 11.0 ± 1.41 | 4.5 ± 0.71 | 5.0 ± 2.00 |
| Day 42 | 8.0 ± 0.00 | 4.0 ± 0.00 | 8.0 ± 2.16 |
| Day 56 | 6.5 ± 2.12 | 5.0 ± 0.00 | 7.4 ± 1.95 |
Collected over From day 1 to day 56.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| rVA576, Open-label Period | 0/3 (0%) | 0/3 (0%) | 3/3 (100%) |
| rVA576, Double-blind Period | 0/3 (0%) | 0/3 (0%) | 2/3 (66.7%) |
| Placebo | 0/6 (0%) | 0/6 (0%) | 3/6 (50%) |
| Event | rVA576, Open-label Period | rVA576, Double-blind Period | Placebo |
|---|---|---|---|
| Ocular hyperaemiaEye disorders | 2/3 | 0/3 | 0/6 |
| Atopic keratoconjunctivitisEye disorders | 1/3 | 1/3 | 0/6 |
| KeratitisEye disorders | 0/3 | 1/3 | 1/6 |
| Dry eyeEye disorders | 0/3 | 1/3 | 0/6 |
| Eczema eyelidsEye disorders | 0/3 | 1/3 | 0/6 |
| Eye dischargeEye disorders | 1/3 | 0/3 | 0/6 |
| Eye pruritusEye disorders | 1/3 | 0/3 | 0/6 |
| Eye swellingEye disorders | 1/3 | 0/3 | 0/6 |
| InsomniaPsychiatric disorders | 1/3 | 0/3 | 0/6 |
| Dry throatRespiratory, thoracic and mediastinal disorders | 1/3 | 0/3 | 0/6 |
| Age, Continuous(years) | rVA576, Open-label Period | rVA576, Double-blind Period | Placebo | Total |
|---|---|---|---|---|
| Mean | 44.3 ± 11.55 | 30.3 ± 6.81 | 33.8 ± 8.04 | 32.7 ± 7.42 |
| Sex: Female, Male(Participants) | rVA576, Open-label Period | rVA576, Double-blind Period | Placebo | Total |
|---|---|---|---|---|
| Female | 0 | 1 | 3 | 4 |
| Male | 3 | 2 | 3 | 8 |
| Race/Ethnicity, Customized(Participants) | rVA576, Open-label Period | rVA576, Double-blind Period | Placebo | Total |
|---|---|---|---|---|
| Not Hispanic or Latino | 3 | 3 | 6 | 12 |
| Asian | 1 | 1 | 1 | 3 |
| White | 1 | 1 | 5 | 7 |
| Other | 1 | 1 | 0 | 2 |
| Indication(Participants) | rVA576, Open-label Period | rVA576, Double-blind Period | Placebo | Total |
|---|---|---|---|---|
| Atopic keratoconjunctivitis (AKC) | 3 | 3 | 2 | 8 |
| Vernal keratoconjunctivitis (VKC) | 0 | 0 | 2 | 2 |
| Seasonal allergic conjunctivitis (SAC) | 0 | 0 | 2 | 2 |
| Perennial allergic conjunctivitis (PAC) | 0 | 0 | 0 | 0 |
| Patient group(Participants) | rVA576, Open-label Period | rVA576, Double-blind Period | Placebo | Total |
|---|---|---|---|---|
| AKC/VKC | 3 | 3 | 4 | 10 |
| SAC/PAC | 0 | 0 | 2 | 2 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Mar 2019 to primary completion in Apr 2020, 13 months.
Results were first posted in Feb 2025, 4 years 9 months after primary completion.
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Studies of the drug tested here: RVA576
AKARI Therapeutics