FIND a DOCTOR for NAION

NAION Clinical Trial Doctor Fact Sheet

Quark Pharmaceuticals and NORDIC have partnered to design and conduct an on demand phase II/III acute Non-arteritic anterior ischemic optic neuropathy (NAION) trial to test a new drug that could protect the optic nerve from further damage due to factors related to acute ischemic injury. Results of the Phase I safety study can be found here.

Neuro-Ophthalmologists in clinical practices and in academic institutions will work together with Quark Pharmaceuticals, the Duke Reading Center, Parexel (CRO), and NORDIC to enroll a maximum of 530 participants. This is an opportunity for Eye care specialists and Neuro-Ophthalmologists to advance NAION care.

  1. Current Status of NAION
  2. NAION Diagnosis
  3. Major Study Inclusion Criteria
  4. Study Intervention
  5. QRK207 Endpoints
  6. Industry and NORDIC Collaboration

1. Current Status of NAION

  • #1 Request from Neuro-Ophthalmologists is to have a Trial on NAION
  • 10,000 - 12,000 new cases yearly in the USA;
  • ~20% develop 2nd eye NAION within 5 years.
  • No proven therapy to improve vision or prevent worsening from presentation
  • No controlled studies to demonstrate treatment of acute NAION in Better Vision
  • Aspirin may reduce the incidence of 2nd eye episodes

NAION is the most common cause of acute optic nerve injury in individuals 50 years or older. The vision loss can appear as blurring in the center or lower or upper portion or the entire vision scene while covering the better eye and viewing with the affected eye. Commonly, patients will complain that they can't see objects below the straight ahead line of sight. The vision loss can worsen over days to a week. Think of the optic nerve as the video cable, connecting your eye (which is like an ultra-sophisticated camera) the brain, which processes the signals from the eye to create your vision. NAION interrupts those signals resulting in defects in your visual field. The poor blood flow to the optic nerve is temporary so it is unlikely a brain stroke. There is no blockage of arteries; therefore, treatments to restore blood flow are not used. If treatment can improve or prevent vision it must be started quickly since NAION, like a stroke of the brain, injures the optic nerve permanently.

Although NAION is not due to blood clots or emboli from the carotid artery or heart, but it is associated with the same risk factors that cause heart attack and stroke. Patients are evaluated for high blood pressure, high cholesterol, diabetes (high blood sugar), heart disease, carotid artery narrowing and sleep disorders.

From the outside the eye appears normal. It is not swollen or red. However, the eye doctor can see abnormal visual acuity (less than "20/20"), there are specific defects in the measure visual field (peripheral vision test), and the part of the optic nerve seen by looking in the eye is swollen.

NAION is not due to blood clots or emboli from the carotid artery or heart, but it is associated with the same risk factors that cause heart attack and stroke. Patients are evaluated for high blood pressure, high cholesterol, diabetes (high blood sugar), heart disease, carotid artery narrowing and sleep disorders.

There is no therapy that has been proven to be effective. There are case series suggesting the benefit of many types of interventions: surgical, medical and via electrical stimulation. However, the vast majority of eye care specialists understand that the data supporting these claims do not meet current standards of evidence.

NAION Epidemiology

  • Usually in patients over age 55
  • Men and women equally affected
  • Most have underlying risk factors for systemic vascular disease (but may be undiagnosed at time of onset)
  • Hypertension, Diabetes, Hypercholesteremia, smoking, sleep apnea
  • Occurs in 3-10 per 100,000 in the US

Visual Prognosis of Affected Eye

  • About 40% improve spontaneously (IONDT)
  • Visual acuity more likely to improve than visual field
  • Disc swelling persists for 6-11 weeks (Hayreh et al., 2007), then becomes pale but not usually cupped
Acutely Swollen Optic Disc

2. NAION Diagnosis

  • Visual acuity loss variable: 20/20 to HM or worse
  • Color vision loss usually mirrors visual acuity
  • Visual field usually shows altitudinal or arcuate defect
  • RAPD always present if unilateral and no abnormality in opposite eye
  • Disc usually hyperemic/swollen
  • Peripapillary flame-shaped hemorrhages often present
Acutely Swollen Injected Optic Disc
RE: Acutely swollen injected optic disc with nerve fiber layer hemorrhages superior border
LE: Opposite optic disc small or normal-sized with little or no cup


Examination of Typical NAION Patient


VA:
  • RE 20/20 Eye Muscles & Lids Normal
  • LE 20/200 Relative afferent pupillary defect LE
Color Plates:
  • RE 9/10
  • LE 4/10
Single Field Analysis Central 24-2 Threshold Test

NAION Considerations at Presentation

  1. Differentiate between NAION and arteritic AION due to temporal arteritis.
  2. Confusion with optic neuritis or optic nerve sheath lesion, or infiltration or infection rare.
  3. Patients with NAION require a complete medical assessment, and exploration for:
    1. History of underlying vascular risk factors
    2. Use of erectile dysfunction drugs
    3. Use of amiodarone
    4. Symptoms of apnea

3. Major Study Eligibility Criteria

Inclusion Criteria:

  1. Diagnosis of first episode of NAION in study eye with symptom onset within 14 days prior to Study Day 1.
  2. Clinical sites evaluate NAION diagnosis with Central Reading Center confirmation (using VF and OCT criteria)
  3. Subjects 50-80 years of age
  4. Best corrected visual acuity in the study eye is better than or equal to 15 letter score at 1 M, using ETDRS at presentation exam
  5. NAION diagnosis requires: Disc edema (seen and documented by site PI)
    • Visual field defects in the study eye consistent with NAION and mean deviation worse than 3.0 dB on HVF using the SITA standard 24-2 testing protocol
    • Relative afferent pupillary defect (unless the fellow eye had previous NAION or other optic nerve or retinal disease that is not exclusionary.
    • OCT peripapillary RNFL thickness > 95th percentile and VF pattern compatible with the diagnosis of NAION as determined by a Central Reading Center.

Exclusion Criteria:

  1. Present use or history of any treatment for the current episode of NAION, including systemic steroids, brimonidine, or traditional Chinese herbal medicine
  2. Prior episode of NAION in the study eye only.
  3. Bilateral acute NAION with bilateral disc swelling at presentation
  4. Clinical evidence of temporal arteritis based on: symptoms or signs, OR C reactive protein (CRP), OR abnormal Westergren sedimentation rate

Early REFERRAL will be Critical !

  • Study enrollment is limited to 14 days from patient reported vision loss
  • Identify a study site in your region (using interactive map)
  • Contact the study site
  • Study sites will complete full diagnosis, determine eligibility, and provide all study details.

4. Study Intervention

  • Intravitreal injection of QPI-1007, a small interfering ribonucleic acid (siRNA) designed to temporarily block cells from producing Caspase 2, which controls cell apoptosis.
  • Prior phase I study suggests the drug has no major side effects.
  • 80% of subjects get active treatment - divided among frequency and dose of drug delivery
  • Intravitreal injection is commonly and safely to treatment macula degeneration, diabetic retina disease, and retina vein occlusion.
  • Participants will be randomized to a treatment arm: 4 to active treatment vs 1 to placebo (4/5 chance for active drug);
  • Study visits are slightly more frequent than standard of care (eg. 8 day follow up);
  • Study involves 8 visits over 12 months.

QPI-1007 Overview

QPI-1007 targets caspase 2 -is a 'small interfering ribonucleic acid', or 'siRNA'. siRNA drugs are designed to temporarily block cells from making specific proteins. QPI-1007 is designed to temporarily block the cells of the body from making a protein called 'caspase 2'. High levels of caspase 2 have been found when cells are damaged due to lack of oxygen. In NAION, nerve cells become damaged because of lack of oxygen. Temporarily stopping the nerve cells in the eye from making caspase 2 after they are damaged could give the cells more time to make repairs which may prevent further loss of vision and possibly improve vision.

5. QRK207 Endpoints

PRIMARY ENDPOINTS

  • Efficacy: proportion of subjects who lose 15 letters or more in BCVA score from Baseline to Month 12.
  • Safety: safety and tolerability of QPI-1007 in recent-onset NAION.

SECONDARY ENDPOINTS

  • Mean change from Day 1 to Month 12 in BCVA score in study eye.
  • Mean change of VF; mean deviation from Day 1 to Month 12 in study eye.
NOTE: subject follow up through Month 12 is key to obtain required 12-month study endpoints!

6. Industry and NORDIC Collaboration

A Nonarteritic Anterior Ischemic Optic Neuropathy Clinical Trial: An Industry and NORDIC Collaboration Kupersmith and Miller: J Neuro-Ophthalmol 2016; 36: 235-237



NORDIC Contact

For questions regarding this webpage or help finding a study doctor please call 212-636-3516 or email info@NORDICclinicaltrials.com.