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Nanocrystalline Gold to Treat Remyelination Failure in Chronic Optic Neuropathy In Multiple Sclerosis (VISIONARY-MS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03536559
Recruitment Status : Recruiting
First Posted : May 24, 2018
Last Update Posted : December 4, 2020
Sponsor:
Collaborator:
Clene Australia Pty Ltd
Information provided by (Responsible Party):
Clene Nanomedicine

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.

Condition or disease Intervention/treatment Phase
Relapsing Remitting Multiple Sclerosis Optic Neuropathy Optic; Neuritis, With Demyelination Drug: CNM-Au8 Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: randomized, double-blind, parallel group, placebo controlled study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: 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
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, DB-PC, Parallel Group Study for the Treatment of Visual Pathway Deficits In Chronic Optic Neuropathy to Assess the Efficacy, Safety, Tolerability and Pharmacokinetics of CNM-Au8 For Remyelination In Multiple Sclerosis
Actual Study Start Date : November 23, 2018
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : September 2022


Arm Intervention/treatment
Experimental: 15mg CNM-Au8
15mg suspension of clean-surfaced, faceted, gold nanocrystals in 60ml of sodium bicarbonate buffered water
Drug: CNM-Au8
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.

Experimental: 30mg CNM-Au8
30mg suspension of clean-surfaced, faceted, gold nanocrystals in 60ml of sodium bicarbonate buffered water
Drug: CNM-Au8
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.

Placebo Comparator: Placebo
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
Placebo is liquid with identical color and taste




Primary Outcome Measures :
  1. Best corrected low contrast letter acuity (BC-LCLA). [ Time Frame: Baseline to 24-weeks ]
    Mean change in BC-LCLA across all eyes as measured by 2.5% low contrast Sloan letter charts.


Secondary Outcome Measures :
  1. Functional Composite Responder Analysis [ Time Frame: Baseline to 24 weeks ]

    The functional composite responder analysis is a multi-component score consisting of changes in each subjects EDSS score in addition to changes in the individual components of the modified MS Functional Composite (m)MSFC scale.

    At each visit, each component is given a score relative to baseline: -1 if threshold is met for worsening, 0 if no changes meet threshold criteria, or +1 if threshold is met for improvement.



Other Outcome Measures:
  1. Multifocal Visual Evoked Potential (mfVEP) Latency [ Time Frame: Every 12 weeks following the 6-month primary endpoint, up to 48-weeks ]
    mfVEP latency is an electrophysiologic measure of remyelination that assesses the speed of conduction of electrical signals in neurons of the visual system.

  2. Multifocal Visual Evoked Potential (mfVEP) Amplitude [ Time Frame: Every 12 weeks following the 6-month primary endpoint, up to 48-weeks ]
    mfVEP amplitude is an electrophysiologic measure of axonal protection that assesses the magnitude of electrical signals in neurons of the visual system.

  3. Full field Visual Evoked Potentials (ff-VEP) latency [ Time Frame: At three month intervals beginning at 12-weeks, up to 48-weeks ]
    ffVEP latency is an electrophysiologic measure of remyelination that assesses the latency of electrical signals conduction in neurons of the visual system.

  4. Full field Visual Evoked Potentials (ff-VEP) amplitude [ Time Frame: At three month intervals beginning at 12-weeks, up to 48-weeks ]
    ffVEP amplitude is an electrophysiologic measure of axonal protection that assesses the magnitude of electrical signals in neurons of the visual system.

  5. Optical Coherence Tomography (OCT) [ Time Frame: At three month intervals beginning at 24-weeks, up to 48-weeks ]
    Measure of optic nerve morphology and retinal layers

  6. Magnetic Resonance Imaging (MRI) [ Time Frame: At three month intervals beginning at 24-weeks, up to 48-weeks ]
    Structural imaging of MS lesions

  7. High Contrast Visual Acuity Testing (HCVA) [ Time Frame: Every 6-weeks, up to 48-weeks ]
    Standard visual acuity testing

  8. Expanded Disability Status Scale (EDSS) [ Time Frame: At three month intervals beginning at 12-weeks, up to 48-weeks ]
    Standardized MS functional scales

  9. 9-Hole Peg Test [ Time Frame: Every 12-weeks, up to 48-weeks ]
    Standardized test of upper body extremity function

  10. Symbol Digit Modality Test (SDMT) [ Time Frame: At three month intervals beginning at 12-weeks, up to 48-weeks ]
    Pattern matching functional scale

  11. National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) [ Time Frame: At three month intervals beginning at 12-weeks, up to 48-weeks ]
    Visual Function Quality of Life Scales

  12. Ten-item Neuro-Ophthalmic Supplement (10-item NOS) [ Time Frame: At three month intervals beginning at 12-weeks, up to 48-weeks ]
    Visual Function Quality of Life Scales

  13. Six-Minute Walk Test (6MWT) [ Time Frame: At three month intervals beginning at 12-weeks, up to 48-weeks ]
    Standardized Measure of Mobility and Exercise Tolerance

  14. Timed 25-Foot Walk Test [ Time Frame: Every 12-weeks, up to 48-weeks ]
    Quantitative mobility and leg function performance test

  15. Individual OR Lesion MRI Analysis [ Time Frame: Week 24 and week 48. ]
    Mean change in optic radiation lesional/non-lesional fibre DTI Divided by the MTR difference from Baseline.

  16. Myelin Water Fraction MRI Analysis [ Time Frame: Week 24 and Week 48 ]
    Myelin Water Fraction (MWF) will be assessed with mcDESPOT imaging

  17. Whole Brian Diffusion Tensor Imaging (DTI) divided by Magnetization Transfer Ratio (MTR) [ Time Frame: Week 24 and week 48 ]
    Mean change in whole brain DTI / MTR from Baseline.

  18. Whole Brian White Matter Diffusion Tensor Imaging (DTI) divided by Magnetization Transfer Ratio (MTR) [ Time Frame: Week 24 and week 48 ]
    Mean change in whole brain white matter DTI / MTR from Baseline.

  19. Whole Brian Lesion Diffusion Tensor Imaging (DTI) divided by Magnetization Transfer Ratio (MTR) [ Time Frame: Week 24 and week 48 ]
    Mean change in whole brain lesion DTI / MTR from Baseline.

  20. Optic Radiation Diffusion Tensor Imaging (DTI) divided by Magnetization Transfer Ratio (MTR) [ Time Frame: Week 24 and week 48 ]
    Mean change in optic radiation DTI / MTR from Baseline.

  21. Optic Radiation Lesion Diffusion Tensor Imaging (DTI) divided by Magnetization Transfer Ratio (MTR) [ Time Frame: Week 24 and week 48 ]
    Mean change in optic lesion radiation DTI / MTR from Baseline.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. At least 18 years of age and up to 55 years of age (inclusive) at Screening.
  2. Clinical diagnosis of Relapsing Multiple Sclerosis (meeting McDonald criteria, 2010) who have had RMS no longer than 15 years from diagnosis.
  3. 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.

  4. 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.

  5. Retinal Nerve Fiber Layer (RNFL) thickness ≥ 70 μm.
  6. Stable disease activity based on the investigator's judgment over the previous 6 months.
  7. 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.
  8. Able to understand and give written informed consent.

Exclusion Criteria:

  1. History of AQP4, MOG Ab(+) status, or ≥ 3 segments lesion in the spinal cord.
  2. Any diagnosis other than RMS that could explain the patient's signs and symptoms.
  3. An acute optic neuritis episode within the prior 6 months.
  4. 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).
  5. Unstable treatment with a disease-modifying therapy (DMT) defined as a treatment change within prior 3-months unless due to intolerability.
  6. Current treatment with immunosuppressive or immunomodulatory therapy other than those approved for the treatment of MS.
  7. Any treatment with drugs known or suspected of producing retinal or optic nerve toxicity including hydroxychloroquine, chloroquine, clofazimine, vigabatrin, or ethambutol.
  8. 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).
  9. 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).
  10. 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).
  11. History of human immunodeficiency virus (HIV), hepatitis C (HepC) virus antibody, or hepatitis B (HepB) virus antibody.
  12. History of gold allergy.
  13. 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).
  14. Patients taking clemastine fumarate, 4-aminopyridine (fampridine), or high dose Biotin (>300 mg/day).
  15. 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.
  16. History or evidence of substance abuse or alcohol abuse within 5 years prior to Screening, including alcoholism; or severe tobacco use (>1 pack/day).
  17. Clinical history of toxic neuropathy (e.g., secondary to treatment with ethambutol, isoniazid, linezolid, gentamycin, chloramphenicol, vincristine, or penicillamine).
  18. Current enrollment in any other drug or device treatment study within 3 months prior to Baseline. Participation in an observational non-interventional study (i.e., no drug or device therapy) is not an exclusion criterion.
  19. Inability to undergo any planned study procedures such as LCLA, VEP, MRI, or OCT; history of severe hypersensitivity to gadolinium-DTPA or reduced renal clearance (GFR must be ≥ 45 mL/min at Screening), claustrophobia; or inability to comply with study requirements based on Investigator judgment.
  20. Patients with clinically significant hepatic or renal dysfunction or clinical laboratory findings that would limit the interpretability of change in liver or kidney function, or those with low platelet counts (< 150 x 10^9 per liter) or eosinophilia (absolute eosinophil count of ≥ 500 eosinophils per microliter) at Screening.
  21. Based on the investigator's judgment, concurrent chronic or acute illness or unstable medical condition that may deteriorate that could confound the results of safety assessments, increase risk to the patient, or lead to difficulty complying with the protocol; including severe disc edema or hemorrhage, any clinically significant cardiac, endocrinological, hematological, hepatic, immunological, metabolic, urological, pulmonary, neurological (any progressive neurological disorder other than RRMS), dermatological, psychiatric (any untreated or unstable psychiatric disease including depression, bipolar and psychosis), renal, severe allergic or anaphylactic reactions, autoimmune, or other major confounding diseases.
  22. Any history of previous malignancy, with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix, post documented full resections, with clean margins.
  23. Patient is considered a suicide risk in the opinion of the Investigator, has previously made a suicide attempt, or is currently demonstrating active suicidal ideation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03536559


Contacts
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Contact: Robert Glanzman, MD 801-676-9695 info@clene.com
Contact: Austin Rynders 801-676-9695 info@clene.com

Locations
Show Show 17 study locations
Sponsors and Collaborators
Clene Nanomedicine
Clene Australia Pty Ltd
Investigators
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Principal Investigator: Heidi Beadnall, MD University of Sydney
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Responsible Party: Clene Nanomedicine
ClinicalTrials.gov Identifier: NCT03536559    
Other Study ID Numbers: CNMAu8.201
First Posted: May 24, 2018    Key Record Dates
Last Update Posted: December 4, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Clene Nanomedicine:
gold
nanocrystal
multifocal visual evoked potential
full field visual evoked potential
low contrast vision
low contrast letter acuity
remyelination
demyelination
Additional relevant MeSH terms:
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Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Optic Nerve Diseases
Neuritis
Demyelinating Diseases
Optic Neuritis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Autoimmune Diseases
Immune System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Cranial Nerve Diseases
Eye Diseases