A Phase I Clinical Trial of DARC

NCT02394613 | Unknown Phase 1 DMC

• 2 other identifiers: 08/03512014-002504-25
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Glaucoma is a major cause of irreversible blindness worldwide, caused by retinal nerve cell (RGC) death. This is currently identified only after significant vision loss has already occurred with an early event in, and a potential marker of, this process being RGC "apoptosis" (a form of cell death). This study aims to investigate the tolerability and safety of ANX776, as part of the new Detection of Apoptosing Retinal Cells (DARC) technique. This has been developed by the laboratory of DARC IP holder and grant applicant: Prof. M. Francesca Cordeiro. A secondary aim is to initially establish the ability of DARC to identify RGC apoptosis in the diagnosis of glaucoma in healthy and progressive glaucoma/glaucoma-suspect/ocular hypertensive patients. As a positive control for this secondary aim of this study, patients with Non-arteritic Anterior Ischaemic Optic Neuropathy (NAION) will be recruited. During the study, each patient will undergo several ophthalmological examinations, imaging of the back of the eye using established clinical devices, and blood sampling for studying the safety and toxicology profile of ANX776. The understanding of the safety profile of ANX776 is crucial for the use of DARC in patients, and its application as a potentially powerful new clinical tool with which to identify patients with early glaucoma before their vision is lost. If successful, it opens the door to directly observing effects of glaucoma treatments, including the assessment of new, breakthrough therapies.

Conditions

Glaucoma; Ocular Hypertension; Glaucoma, Suspect

Keywords

Glaucoma; DARC; Diagnosis

Outcome Measures

Primary Outcomes (1)

• Safety of ANX776 as defined by the number and nature of adverse events

  Serious and adverse medical events will be recorded

  24 hours

Secondary Outcomes (1)

• DARC Count

  6 hours

Study Arms (1)

ANX776

EXPERIMENTAL

Using and increasing dose storer design, GLAUCOMA and NORMAL patients will be randomly grouped to received the intervention (0.1 mg, 0.2 mg, 0.4 mg, 0.5 mg). 1 NAION patient will receive each dose once it has been proven safe in GLAUCOMA and NORMAL patients, as part of the secondary objective of this trial.

Drug: ANX776

Interventions

ANX776 DRUG

Single intravenous injection

ANX776

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years
• Clear optical media in the studied eye
• No ocular or systemic disease (except glaucoma in the test group)
• Refractive error not higher than spherical equivalent of 6D; best corrected visual acuity ≥ 6/24 at qualification
• Proven ability to perform reliable visual field testing (HFA 640, central 24-2 program) to yield full thresholds, and have had good fundoscopy with assessment of the optic disc
• Willing and able to comply with the scheduled visits and assessments. Informed Consent Form personally (or by legal representative) signed and dated
• Women Not of Childbearing Potential (postmenopausal or permanently sterilised)
• Male participants agree to double barrier contraception from consent until 6 weeks after treatment discontinuation
• GLAUCOMA patients
• Show progression in any measured parameter; have at least one eye with a diagnosis of glaucoma (abnormal optic disc, visual field defect or both); be diagnosed as a glaucoma suspect or ocular hypertensive (elevated Intraocular Pressure (IOP))
• NORMAL subjects
• No evidence of any glaucomatous process (either optic disc, Retinal Nerve Fibre Layer (RNFL) of visual field abnormalities with normal IOPs)
• Must provide a GP letter confirming their medical history
• GLAUCOMA \& NORMAL patients • Have performed at least 3 Visual Field tests, Heidelberg Retinal Tomography (HRT), and Optical Coherence Tomography (OCT) before or during Visit-1
• POSITIVE CONTROL patients

You may not qualify if:

• Terminal or mental illness, dementia, inability to comply with the study or follow-up procedures
• Presence of ocular or systemic uncontrolled disease (unless deemed not clinically significant by Chief Investigator and Sponsor), except glaucoma in the test group
• Central corneal thickness \<450µm or \>650µm
• History of current or severe, unstable or uncontrolled systemic disease (unless deemed not clinically significant by Chief Investigator and Sponsor)
• Body weight \<40kg or \>120kg
• Evidence of another chronic neurodegenerative condition
• Patients with active antiphospholipid syndrome or with diagnosis of circulating antiphospholipid antibodies
• History of clotting diseases (including Deep Vein Thromboses), subjects taking anticoagulants
• Diagnosis of thrombocytopenia, heart valve disease, and livedo reticularis
• Pregnancy or lactation
• Allergy to any study medication ingredient
• Ocular surgery within the past 3 months in the study eye
• History of retinal laser photocoagulation
• Media opacities or retinal pathology or amblyopia significantly limiting visual acuity, visual field test or retinal imaging
• Expected need for ocular surgery during the study

Sponsors & Collaborators

• University College, London: lead
• Wellcome Trust: collaborator

Study Sites (1)

Western Eye Hospital, Imperial College Healthcare NHS Trust,

London, NW1 5QH, United Kingdom

Location

MeSH Terms

Conditions

Glaucoma; Ocular Hypertension; Disease

Condition Hierarchy (Ancestors)

Eye Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Philip Bloom, MB ChB FRCS

  Western Eye Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2015
• First Posted: March 20, 2015
• Study Start: May 1, 2015
• Primary Completion: November 1, 2015
• Study Completion: August 1, 2016
• Last Updated: May 26, 2016

Record last verified: 2015-08

Locations

GB (1)