AzTrials
AzTrials

Relapsing Remitting Multiple SclerosisPhase 2VISIONARY-MSNCT03536559

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

A Phase 2 study testing CNM-Au8 in people with Relapsing Remitting Multiple Sclerosis and Optic Neuropathy, run by Clene Nanomedicine at 7 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 55 years
What is being tested?
CNM-Au8
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
73 participants
Where
7 sitesin 3 countries
Study dates
23 Nov 2018to 12 Jul 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.
  • 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.
  • 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.
Show all 10Show fewer
  • 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.

Who cannot join

  • 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.
Show all 23Show fewer
  • 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.
  • History or evidence of substance abuse or alcohol abuse within 5 years prior to Screening, including alcoholism; or severe tobacco use (>1 pack/day).
  • Clinical history of toxic neuropathy (e.g., secondary to treatment with ethambutol, isoniazid, linezolid, gentamycin, chloramphenicol, vincristine, or penicillamine).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Trial locations and contacts

7 sites in 3 countries.

7 sites in 3 countries

Australia5 sites
  • Menzies Institute for Medical Research

    Hobart, Tasmania, 7000

  • Alfred Health

    Melbourne, Victoria, 3004

  • John Hunter Hospital

    New Lambton Heights, New South Wales, 2305

  • Sydney Brain Mind Centre

    Sydney, New South Wales

  • Princess Alexandria Hospital

    Woolloongabba, Queensland, 4102

Other trials in Australia

United States1 site
  • UT Southwestern Medical Center

    Dallas, Texas, 75390

Other trials in United States

Canada1 site
  • University of British Columbia

    Vancouver, British Columbia, V6T 1Z3

Other trials in Canada

About this study

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

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.

Read the detailed description

This is a randomized, double-blind, parallel-group, placebo-controlled study of the efficacy, safety, and pharmacokinetics of CNM-Au8 in stable RRMS patients who have Chronic Optic Neuropathy evidence by low contrast letter acuity deficits at Screening.

Patients will be screened over a 6-week period. Patients who meet the inclusion criteria and none of the exclusionary criteria will be enrolled into the clinical study.

All enrolled patients will have their visual baseline established in both eyes by functional, electrophysiological (at participating research sites), and morphological tests.

For each patient, the eye with the worst Baseline LCLA score will be considered as the affected eye. The other eye will be considered as the fellow eye. If both eyes have the same LCLA score at Baseline, then one eye will be randomly selected by the statistician to assess as the designated affected eye. Efficacy endpoints will be assessed in both the affected and the fellow eyes. Patients will be randomized to one of three groups: placebo, or one of two doses of CNM-Au8. All patients will receive their randomized investigational product (IP) dose daily over at least 24 consecutive weeks during the Fixed Duration Treatment Period. The study will also have a blinded Variable Duration Treatment Period for up to an additional 24-weeks (up to a 48-week maximum blinded duration) until the last-patient enrolled completes his/her Week 24 study visit per the study scheme in Figure 2. When the last enrolled patient completes his or her Week 24 visit, patients enrolled in the Variable Duration Treatment Period will complete the End-of-Study (EOS) visit at their next scheduled study visit.

The primary efficacy outcome measure will be assessed Efficacy will be assessed as an improvement in best-corrected low contrast letter acuity (BC-LCLA). Safety will be assessed up through the frequency of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and discontinuations due to adverse events (AEs), and changes in safety assessments (e.g., vitals, ECG, C-SSRS).

The study will remain blinded until the study database is locked.

All patients who are discontinued from treatment will complete the End-of-Study (EOS) assessment.

At the end of the Variable Duration Treatment Period, patients will complete an EOS assessment and then may choose either to exit the study, or receive open-label CNM-Au8 in a separate Open-Label Safety Extension Study.

An independent DSMB will be responsible for monitoring the safety of the study on a quarterly basis and ad hoc at the request of the DSMB or the Sponsor (e.g., in the event of unexpected SAEs) to review data throughout the Fixed Duration Treatment Period and the Variable Duration Treatment Period. The DSMB may make recommendations on the conduct of the study, including study termination. Appropriate procedures will be detailed in a DSMB Charter that will define disclosure of any findings along with patient- and study-stopping criteria.

There will be four study periods:

  1. A six-week screening period (Screening Period);
  2. A fixed 24-week double-blind, randomized treatment period (Fixed Duration Treatment Period);
  3. A variable-duration, double-blind treatment period (Variable Duration Treatment Period) where patients continue the previously randomized treatment for up to an additional 24 weeks (total blinded duration of 48- weeks). This period will end for all patients when the last-enrolled patient reaches his or her 24-week visit (LP-24Wk) at which time patients in the Variable Duration Treatment Period will complete the EOS Visit at their next scheduled study visit;
  4. A four-week follow-up period (Safety Follow-Up Period) for patients not continuing in the separate Open-Label Long-Term Safety Extension Study.

Following the end of the blinded treatment period, all patients who complete the 24-week Fixed Duration Treatment Period may be eligible to receive open-label CNM-Au8 in a separate Open-Label Long-Term Safety Extension Study.

Being tested
CNM-Au8, Placebo
Keywords
gold, nanocrystal, multifocal visual evoked potential, full field visual evoked potential, low contrast vision, low contrast letter acuity, remyelination, demyelination
Medical subject headings
Multiple Sclerosis, Relapsing-Remitting, Optic Nerve Diseases, Neuritis, Demyelinating Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CNM-Au8Drug

    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.

  • PlaceboDrug

    Placebo is liquid with identical color and taste

Study groups in NCT03536559
Study groupRoleWhat they receive
15mg CNM-Au8Experimental15mg suspension of clean-surfaced, faceted, gold nanocrystals in 60ml of sodium bicarbonate buffered water
Receives: Drug: CNM-Au8
30mg CNM-Au8Experimental30mg suspension of clean-surfaced, faceted, gold nanocrystals in 60ml of sodium bicarbonate buffered water
Receives: Drug: CNM-Au8
PlaceboPlacebo comparatorThe 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline to 48 weeks

Secondary outcomes (1)
  1. Other Measures of Neurological Function

    Change in the MS Functional Composite assessed by:

    Change from baseline for the average of the Z-scores of the six (m)MSFC domains.

    Combined ranked sum score for each (m)MSFC domain to the end of study. Time to the first repeated improvement of any two (m)MSFC domains by >=15%.

    Measured: Baseline up to 48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 May 2018
  2. Study start23 Nov 2018
  3. Primary completion27 Apr 2022
  4. Study completion12 Jul 2022

Why it stopped: COVID-19 related enrollment challenges.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
randomized, double-blind, parallel group, placebo controlled study
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
73 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03536559
Sponsor's protocol ID
CNMAu8.201
Acronym
VISIONARY-MS
Status last verified
Mar 2023
First submitted
2 May 2018
Last updated
3 Apr 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CNM-Au8 in people with Relapsing Remitting Multiple Sclerosis and Optic Neuropathy, run by Clene Nanomedicine at 7 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 3 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Australia, United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: COVID-19 related enrollment challenges.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Measures of Visual Function (time frame: Baseline to 48 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2023.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in