Topical rVA576 for Treatment of Atopic Keratoconjunctivitis

Akari Therapeutics

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Conjunctivitis, Allergic; Keratoconjunctivitis, Atopic; Keratoconjunctivitis, Vernal

Treatments: Other: Placebo; Drug: rVA576

Study type: Interventional

Funder types: Industry

Identifiers

NCT04037891

AK701

Details and patient eligibility

About

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)

Full 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).

Enrollment: 12 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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12 participants in 3 patient groups, including a placebo group

rVA576 - Open-label period

Experimental group

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

Treatment:

Drug: rVA576

Drug: rVA576

Placebo - Double-blind period

Placebo Comparator group

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.

Treatment:

Other: Placebo

rVA576 - Double-blind period

Experimental group

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.

Treatment:

Drug: rVA576

Drug: rVA576