A Phase 2 interventional study of CNM-Au8 and Placebo in Relapsing Remitting Multiple Sclerosis, Optic Neuropathy and Optic; Neuritis, With Demyelination, sponsored by Clene Nanomedicine. Terminated at 7 sites in 3 countries. Open to participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2023-04-03.
Sponsored by Clene Nanomedicine · Phase 2, Interventional, and Treatment
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.
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:
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.
618 studies on the registry are indexed under Multiple Sclerosis, Relapsing-Remitting; 82 are open to participants now.
This study's enrollment of 73 is above the median of 66 across 437 interventional studies indexed under Multiple Sclerosis, Relapsing-Remitting.
Browse Multiple Sclerosis, Relapsing-Remitting studies →Clene Nanomedicine is the lead sponsor of 12 studies on the registry; 1 is open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 2 (40%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
15mg suspension of clean-surfaced, faceted, gold nanocrystals in 60ml of sodium bicarbonate buffered water
Drug: CNM-Au8
30mg suspension of clean-surfaced, faceted, gold nanocrystals in 60ml of sodium bicarbonate buffered water
Drug: CNM-Au8
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
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 is liquid with identical color and taste
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.
Time frame: Baseline to 48 weeks
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%.
Time frame: Baseline up to 48 weeks
Multifocal Visual Evoked Potential (mfVEP) Latency
mfVEP latency is an electrophysiologic measure of remyelination that assesses the speed of conduction of electrical signals in neurons of the visual system.
Time frame: Every 12 weeks following the 6-month primary endpoint, up to 48-weeks
Multifocal Visual Evoked Potential (mfVEP) Amplitude
mfVEP amplitude is an electrophysiologic measure of axonal protection that assesses the magnitude of electrical signals in neurons of the visual system.
Time frame: Every 12 weeks following the 6-month primary endpoint, up to 48-weeks
Full field Visual Evoked Potentials (ff-VEP) latency
ffVEP latency is an electrophysiologic measure of remyelination that assesses the latency of electrical signals conduction in neurons of the visual system.
Time frame: At three month intervals beginning at 12-weeks, up to 48-weeks
Full field Visual Evoked Potentials (ff-VEP) amplitude
ffVEP amplitude is an electrophysiologic measure of axonal protection that assesses the magnitude of electrical signals in neurons of the visual system.
Time frame: At three month intervals beginning at 12-weeks, up to 48-weeks
Optical Coherence Tomography (OCT)
Measure of optic nerve morphology and retinal layers
Time frame: At three month intervals beginning at 24-weeks, up to 48-weeks
Magnetic Resonance Imaging (MRI)
Structural imaging of MS lesions
Time frame: At three month intervals beginning at 24-weeks, up to 48-weeks
Change in Best High Contrast Visual Acuity Testing (HCVA)
Mean change from Baseline in best-corrected high contrast visual acuity (BC-HCVA) score, as measured by EDTRS in the affected and fellow eye.
Time frame: Every 6-weeks, up to 48-weeks
Expanded Disability Status Scale (EDSS)
Standardized MS functional scales
Time frame: At three month intervals beginning at 12-weeks, up to 48-weeks
9-Hole Peg Test
Standardized test of upper body extremity function
Time frame: Every 12-weeks, up to 48-weeks
Symbol Digit Modality Test (SDMT)
Pattern matching functional scale
Time frame: At three month intervals beginning at 12-weeks, up to 48-weeks
National Eye Institute Visual Function Questionnaire (NEI-VFQ-25)
Visual Function Quality of Life Scales
Time frame: At three month intervals beginning at 12-weeks, up to 48-weeks
Ten-item Neuro-Ophthalmic Supplement (10-item NOS)
Visual Function Quality of Life Scales
Time frame: At three month intervals beginning at 12-weeks, up to 48-weeks
Six-Minute Walk Test (6MWT)
Standardized Measure of Mobility and Exercise Tolerance
Time frame: At three month intervals beginning at 12-weeks, up to 48-weeks
Timed 25-Foot Walk Test
Quantitative mobility and leg function performance test
Time frame: Every 12-weeks, up to 48-weeks
Individual OR Lesion MRI Analysis
Mean change in optic radiation lesional/non-lesional fibre DTI Divided by the MTR difference from Baseline.
Time frame: Week 24 and week 48.
Myelin Water Fraction MRI Analysis
Myelin Water Fraction (MWF) will be assessed with mcDESPOT imaging
Time frame: Week 24 and Week 48
Whole Brian Diffusion Tensor Imaging (DTI) divided by Magnetization Transfer Ratio (MTR)
Mean change in whole brain DTI / MTR from Baseline.
Time frame: Week 24 and week 48
Whole Brian White Matter Diffusion Tensor Imaging (DTI) divided by Magnetization Transfer Ratio (MTR)
Mean change in whole brain white matter DTI / MTR from Baseline.
Time frame: Week 24 and week 48
Whole Brian Lesion Diffusion Tensor Imaging (DTI) divided by Magnetization Transfer Ratio (MTR)
Mean change in whole brain lesion DTI / MTR from Baseline.
Time frame: Week 24 and week 48
Optic Radiation Diffusion Tensor Imaging (DTI) divided by Magnetization Transfer Ratio (MTR)
Mean change in optic radiation DTI / MTR from Baseline.
Time frame: Week 24 and week 48
Optic Radiation Lesion Diffusion Tensor Imaging (DTI) divided by Magnetization Transfer Ratio (MTR)
Mean change in optic lesion radiation DTI / MTR from Baseline.
Time frame: Week 24 and week 48
Change in Best Corrected Low-Contrast Letter Acuity (BC-LCLA)
Mean change by eye from Baseline in BC-LCLA score as determined by 2.5% low contrast Sloan letter chart for the affected and fellow eye. Proportion of patients with an improvement of at least 7 character letters by 2.5% low contrast Sloan letter chart in the affected and fellow eye.
Time frame: Baseline up to 48 weeks
Plan to share: No
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Ran from Nov 2018 to primary completion in Apr 2022, 41 months.
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This study is terminated, as verified in Mar 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: CNM-Au8
Multiple Sclerosis, Relapsing-Remitting →
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