Topical rVA576 for Treatment of Atopic Keratoconjunctivitis

NCT04037891 | Terminated Phase 1 Results DMC

• 1 other identifier: AK701
• Study Type: interventional
• Target: 12
• Locations: 2 countries
• Sites: 9

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)

Conditions

Keratoconjunctivitis, Atopic; Keratoconjunctivitis, Vernal; Conjunctivitis, Allergic

Outcome Measures

Primary Outcomes (1)

• 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.

  56 days

Secondary Outcomes (5)

• Post-instillation Comfort

  Day 1 to 56

• Visual Acuity

  Day 1 to 56

• Clinical Scores

  Day 1 to 56

• MMP-9 Positive

  Day 1 to 56

• Tear Film Break up Time

  Change from Day 1 at Day 14, 28, 42 and 56

Study Arms (3)

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

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.

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.

Drug: rVA576

Interventions

rVA576 DRUG

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

Also known as: Nomacopan

rVA576 - Open-label period

Placebo 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.

Placebo - Double-blind period

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• AKARI Therapeutics: lead

Study Sites (9)

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Instituto Universitario de Oftalmobiología Aplicada

Valladolid, Spain

Location

Bristol Eye Hospital

Bristol, United Kingdom

Location

Addenbrookes Hospital

Cambridge, United Kingdom

Location

St James's University Hospital

Leeds, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, United Kingdom

Location

Moorfields Eye Hospital NHS Foundation Trust

London, EC1V 2PD, United Kingdom

Location

Royal Victoria Infirmary

Newcastle upon Tyne, United Kingdom

Location

University Hospital NHS Foundation Trust

Southend-on-Sea, United Kingdom

Location

MeSH Terms

Conditions

Keratoconjunctivitis; Conjunctivitis, Allergic

Condition Hierarchy (Ancestors)

Conjunctivitis; Conjunctival Diseases; Eye Diseases; Keratitis; Corneal Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Limitations and Caveats

1. Early termination due to the Covid-19 pandemic. 2. Uneven distribution of patients between rVA576 and placebo in Part 2, due to incorrect storage and impossibility of manufacturing a new batch, leading to replacement by the only available randomized and labelled product and resulting in patients being allocated to placebo. With a 6 to 3 distribution of completed patients it is difficult to draw meaningful statistical conclusions or detect trends. The safety data were not compromised.

Results Point of Contact

• Title: Wynne H Weston-Davies
• Organization: Akari

wynne.weston-davies@akaritx.com

+44(0)7801 281283

Study Officials

• Sajjad Ahmad

  Moorfields Eye Hospital NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Randomised, double-masked, placebo-controlled parallel group comparison with open-label sentinel group.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2019
• First Posted: July 30, 2019
• Study Start: March 4, 2019
• Primary Completion: April 30, 2020
• Study Completion: April 30, 2020
• Last Updated: April 10, 2025
• Results First Posted: February 27, 2025

Record last verified: 2024-07

Locations

GB (7); ES (2)