Nanocrystalline Gold to Treat Remyelination Failure in Chronic Optic Neuropathy In Multiple Sclerosis

NCT03536559 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: CNMAu8.201
• Study Type: interventional
• Target: 73
• Locations: 3 countries
• Sites: 7

Brief Summary

The objective of this trial is to assess the efficacy and safety of CNM-Au8 as a remyelinating treatment for vision-impairing MS lesions in participants who have chronic vision impairment as a result of Relapsing-Remitting Multiple Sclerosis. The primary endpoint is to assess the efficacy and safety of CNM-Au8 as a remyelinating therapy in patients with stable RMS. The secondary endpoint is Change in Functional Composite Responder Analysis Score from Baseline to Week 24.

Conditions

Relapsing Remitting Multiple Sclerosis; Optic Neuropathy; Optic; Neuritis, With Demyelination

Keywords

gold; nanocrystal; multifocal visual evoked potential; full field visual evoked potential; low contrast vision; low contrast letter acuity; remyelination; demyelination

Outcome Measures

Primary Outcomes (1)

• Measures of Visual Function

  Change in Best-Corrected Low-Contrast Letter Acuity (BC-LCLA) score: Mean change in BC-LCLA from Baseline to Week 48 in the most affected eye as measured by 2.5% low contrast Sloan letter charts.

  Baseline to 48 weeks

Secondary Outcomes (1)

• Other Measures of Neurological Function

  Baseline up to 48 weeks

Other Outcomes (22)

• Multifocal Visual Evoked Potential (mfVEP) Latency

  Every 12 weeks following the 6-month primary endpoint, up to 48-weeks

• Multifocal Visual Evoked Potential (mfVEP) Amplitude

  Every 12 weeks following the 6-month primary endpoint, up to 48-weeks

• Full field Visual Evoked Potentials (ff-VEP) latency

  At three month intervals beginning at 12-weeks, up to 48-weeks

Study Arms (3)

15mg CNM-Au8

EXPERIMENTAL

15mg suspension of clean-surfaced, faceted, gold nanocrystals in 60ml of sodium bicarbonate buffered water

Drug: CNM-Au8

30mg CNM-Au8

EXPERIMENTAL

30mg suspension of clean-surfaced, faceted, gold nanocrystals in 60ml of sodium bicarbonate buffered water

Drug: CNM-Au8

Placebo

PLACEBO COMPARATOR

The matched placebo to be used in this study will consist of water, sodium bicarbonate, and food coloring to match volume and color of the experimental treatments.

Drug: Placebo

Interventions

CNM-Au8 DRUG

CNM-Au8 is a dark red/purple-colored liquid formulation consisting of a stable suspension of faceted clean surfaced elemental gold nanocrystals in buffered deionized water with a concentration of up to 0.5 mg/mL of gold. The formulation is buffered by sodium bicarbonate present at a concentration of 0.546 mg/mL. There are no other excipients. The drug product is formulated to be taken orally and will be provided in single dose HDPE containers. The study doses vary by the concentration of gold nanocrystals per milliliter in a volume of 60 mL.

15mg CNM-Au8; 30mg CNM-Au8

Placebo DRUG

Placebo is liquid with identical color and taste

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• At least 18 years of age and up to 55 years of age (inclusive) at Screening.
• Clinical diagnosis of Relapsing Multiple Sclerosis (meeting McDonald criteria, 2010) who have had RMS no longer than 15 years from diagnosis.
• Maximum Best Corrected High Contrast Visual Acuity (BC-HCVA) deficit on the Early Treatment Diabetic Retinopathy Study (ETDRS) Chart of 20/200 (6/60 metric) in both eyes.
• a. BC-HCVA is defined as the last line on the Early Treatment Diabetic Retinopathy Study (ETDRS) Chart that a patient is able to read three (3) or more letters correctly.
• Best Corrected Low Contrast Letter Acuity (BC-LCLA) (by 2.5% Sloan Chart) must be 20/40 (6/12 metric) (inclusive) or worse in the affected eye and 20/32 (6/9.5 metric) or worse in the fellow eye; and the BC-LCLA must be worse than BC-HCVA for the respective value in both eyes.
• a. BC-LCLA is defined as the last line on the 2.5% Sloan Chart that a patient is able to read three (3) or more letters correctly.
• Retinal Nerve Fiber Layer (RNFL) thickness ≥ 70 μm.
• Stable disease activity based on the investigator's judgment over the previous 6 months.
• All hematological parameters and biochemical parameters that fall outside the Within Normal Limits range must be assessed as Not Clinically Significant (NCS) and deemed stable or transient in nature.
• Able to understand and give written informed consent.

You may not qualify if:

• History of AQP4, MOG Ab(+) status, or ≥ 3 segments lesion in the spinal cord.
• Any diagnosis other than RMS that could explain the patient's signs and symptoms.
• An acute optic neuritis episode within the prior 6 months.
• Clinical relapse requiring systemic steroid treatment within the prior 3 months (pre- treatment with systemic steroids during the administration of disease-modifying therapies \[DMT\] may be allowed after discussion with the Sponsor's Medical Monitor but must not be administered within 30 days of a planned VEP or MRI assessment).
• Unstable treatment with a disease-modifying therapy (DMT) defined as a treatment change within prior 3-months unless due to intolerability.
• Current treatment with immunosuppressive or immunomodulatory therapy other than those approved for the treatment of MS.
• Any treatment with drugs known or suspected of producing retinal or optic nerve toxicity including hydroxychloroquine, chloroquine, clofazimine, vigabatrin, or ethambutol.
• Any history of ophthalmological cause for retinal damage other than MS (e.g. cataracts, uveitis, macular degeneration, macular exudate, macular edema, glaucoma, severe astigmatism, ocular trauma, neuromyelitis optica, ischemic optic neuropathy, congenital nystagmus, retinal detachment, amblyopia, optic disk drusen).
• Severe refractive defects: refractive errors (-6 dioptres to +6 dioptres or more in either eye, or axial eye length \>26 mm), hypermetropia (\> 6 dioptres; cylinder \> 3 dioptres); or based on the investigators judgment any other ophthalmic diseases that would confound the study results or assessment of Visual Evoked Potential (VEPs), Best Corrected Visual Acuity (BCVA), Low Contrast Letter Acuity (LCLA), or Optical Coherence Tomography (OCT).
• History diabetic retinopathy or a previous diagnosis of Diabetes Mellitus or history of prior impaired fasting glucose ≥126 mg/dL (or ≥ 200 mg/dL after oral glucose tolerance test).
• History of human immunodeficiency virus (HIV), hepatitis C (HepC) virus antibody, or hepatitis B (HepB) virus antibody.
• History of gold allergy.
• Patients taking stimulant medications (including: amphetamine, dextroamphetamine, lisdexamfetamine, methylphenidate, or modafinil) who have not been on a stable dose greater than or equal to 30 days. Changes to dose will not be allowed during the course of the trial).
• Patients taking clemastine fumarate, 4-aminopyridine (fampridine), or high dose Biotin (\>300 mg/day).
• Females who have a positive serum pregnancy test result at Screening or Baseline, or who are pregnant, breastfeeding, or planning to conceive during the study or within 180 days after study completion.

Sponsors & Collaborators

• Clene Nanomedicine: lead
• Clene Australia Pty Ltd.: collaborator

Study Sites (7)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

John Hunter Hospital

New Lambton Heights, New South Wales, 2305, Australia

Location

Sydney Brain Mind Centre

Sydney, New South Wales, Australia

Location

Princess Alexandria Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Menzies Institute for Medical Research

Hobart, Tasmania, 7000, Australia

Location

Alfred Health

Melbourne, Victoria, 3004, Australia

Location

University of British Columbia

Vancouver, British Columbia, V6T 1Z3, Canada

Location

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Optic Nerve Diseases; Neuritis; Demyelinating Diseases

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Cranial Nerve Diseases; Eye Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Study Officials

• Heidi Beadnall, MD

  University of Sydney

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The drug formulations will be identical in appearance (size, shape, volume, color) and smell. The packaging and labeling will be designed to maintain blinding to the Investigator's team and to patients. There are no visible differences between the active drug, and placebo dosing units
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: randomized, double-blind, parallel group, placebo controlled study

Study Record Dates

• First Submitted: May 2, 2018
• First Posted: May 24, 2018
• Study Start: November 23, 2018
• Primary Completion: April 27, 2022
• Study Completion: July 12, 2022
• Last Updated: April 3, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (1); AU (5)