Topical rVA576 for Treatment of Atopic Keratoconjunctivitis

NCT ID: NCT04037891

Last Updated: 2025-04-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-04
• Study Completion Date: 2020-04-30

Brief 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)

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).

Conditions

Keratoconjunctivitis, Atopic; Keratoconjunctivitis, Vernal; Conjunctivitis, Allergic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

rVA576 - Open-label period

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

Group Type: EXPERIMENTAL

rVA576

Intervention Type: DRUG

Part 1: The first 3 patients selected for the study will be treated with the active drug in open-label.

Placebo - Double-blind period

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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.

rVA576 - Double-blind period

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.

Group Type: EXPERIMENTAL

rVA576

Intervention Type: DRUG

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.

Interventions

rVA576

Part 1: The first 3 patients selected for the study will be treated with the active drug in open-label.

Intervention Type: DRUG

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.

Intervention Type: OTHER

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.

Intervention Type: DRUG

Other Intervention Names

Nomacopan; Nomacopan

Eligibility Criteria

Inclusion Criteria

1. Aged 18 and above

2. 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

3. 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.

4. Will have had at least 7 days without topical ocular corticosteroids prior to entry

5. Willing to give informed consent

6. Willing to use highly effective contraceptive precautions for the duration of the study and for 90 days after the last dose of IMP

7. Willing to avoid prohibited medications for duration of study (see list of prohibited medications)

Exclusion Criteria

1. Eye surface disease other than AKC, VKC or severe allergic conjunctivitis (SAC or PAC)

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. Uncontrolled glaucoma (increase in dose of glaucoma medication or surgical intervention for glaucoma within 3 months prior to entry)

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. Use of topical ocular steroids within 7 days of the Screening visit

16. Failure to satisfy the PI of suitability to participate for any other reason

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AKARI Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sajjad Ahmad

Role: PRINCIPAL_INVESTIGATOR

Moorfields Eye Hospital NHS Foundation Trust

Locations

Hospital Clinic de Barcelona

Barcelona, , Spain

Instituto Universitario de Oftalmobiología Aplicada

Valladolid, , Spain

Bristol Eye Hospital

Bristol, , United Kingdom

Addenbrookes Hospital

Cambridge, , United Kingdom

St James's University Hospital

Leeds, , United Kingdom

Royal Liverpool University Hospital

Liverpool, , United Kingdom

Moorfields Eye Hospital NHS Foundation Trust

London, , United Kingdom

Royal Victoria Infirmary

Newcastle upon Tyne, , United Kingdom

University Hospital NHS Foundation Trust

Southend-on-Sea, , United Kingdom

Countries

Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

AK701

Identifier Type: -

Identifier Source: org_study_id