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31P-MRS Imaging to Assess the Effects of CNM-Au8 on Impaired Neuronal Redox State in Multiple Sclerosis (REPAIR-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: NCT03993171
Recruitment Status : Recruiting
First Posted : June 20, 2019
Last Update Posted : January 18, 2020
Sponsor:
Collaborator:
University of Texas Southwestern Medical Center
Information provided by (Responsible Party):
Clene Nanomedicine

Brief Summary:
REPAIR-MS is a single-center open label, sequential group, investigator and patient blinded study to assess the CNS metabolic effects, safety, pharmacokinetics, and pharmacodynamics of CNM-Au8 in patients who have been diagnosed with Multiple Sclerosis (MS) within fifteen (15) years of Screening. The primary endpoint is the ratio of the oxidized to reduced form of nicotinamide adenine dinucleotide (NAD+:NADH) measured non-invasively by 31phosphorous magnetic resonance spectroscopy (31P-MRS).

Condition or disease Intervention/treatment Phase
Relapsing Remitting Multiple Sclerosis Drug: gold nanocrystals Phase 2

Detailed Description:

This is a single-center open label, sequential group, investigator blinded study of the CNS metabolic effects, safety, pharmacokinetics, and pharmacodynamics of CNM-Au8 in patients who have been diagnosed with Multiple Sclerosis (MS) within fifteen years of Screening. The Sponsor will select a starting treatment dose of CNM-Au8 for the initial treatment. Investigators and patients will be blinded to each cohort's study dose. Upon completion of the first treatment cohort, the Sponsor will select a single dose or two different doses for the subsequent second cohort from a pre-specified dosing selection plan based on the evaluation of the 31P-Magnetic Resonance Spectroscopy (31P-MRS) changes versus baseline in the first cohort. Up to a total of two treatment cohorts may be studied (n=12 patients/cohort, total n=24 patients). All patients will receive daily oral treatment over twelve consecutive weeks during each cohort's Treatment Period.

There will be three study periods per treatment cohort:

A four-week screening period (Screening Period); A twelve-week treatment period (Treatment Period); A six-week follow-up period (End-of-Study Assessment). The primary study outcome, CNS metabolic changes, will be assessed based upon each patient's Week 12 study visit versus the pre-treatment baseline. The primary endpoint is the brain metabolic effects of treatment with CNM-Au8 as assessed by an improvement of 31P-MRS assessment of Brain Tissue Cellular Redox Potential defined by the measured tissue ratio of NAD+:NADH concentrations following 12 weeks of once daily treatment.

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Study Type : Interventional
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Open Label, Investigator Blinded, Sequential Cohort (max of 2 cohorts amongst the possible 4 interventions)
Masking: None (Open Label)
Masking Description: Research participants and site personnel are not masked to study drug, but will be blinded to study dose for each cohort (single-blinded).
Primary Purpose: Treatment
Official Title: A Phase 2, Open Label, Sequential Group, Investigator Blinded Study of Magnetic Resonance Spectroscopy (31P-MRS) to Assess the Effects of CNM-Au8 for the Bioenergetic Improvement of Impaired Neuronal Redox State in Multiple Sclerosis
Estimated Study Start Date : January 2020
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 7.5mg CNM-Au8
7.5mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water
Drug: gold nanocrystals
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.
Other Name: CNM-Au8

Experimental: 15mg CNM-Au8
15mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water
Drug: gold nanocrystals
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.
Other Name: CNM-Au8

Experimental: 30mg CNM-Au8
30mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water
Drug: gold nanocrystals
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.
Other Name: CNM-Au8

Experimental: 60mg CNM-Au8
60mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water
Drug: gold nanocrystals
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.
Other Name: CNM-Au8




Primary Outcome Measures :
  1. Change in 31P-MRS Redox Ratio (NAD+/NADH) [ Time Frame: At 12 Weeks ]
    Mean change in average NAD+/NADH measured brain Redox Ratio by treatment group


Other Outcome Measures:
  1. Mean Change in 31P-MRS Bioenergetic Metabolite CNS Tissue Concentration of NAD+ [ Time Frame: At 12 Weeks ]
    Mean change in average CNS concentration of NAD+ [mmol/kg] by treatment group

  2. Mean Change in 31P-MRS Bioenergetic Metabolite CNS Tissue Concentration of NADH [ Time Frame: At 12 Weeks ]
    Mean change in average CNS concentration of NADH [mmol/kg] by treatment group

  3. Mean Change in 31P-MRS Bioenergetic Metabolite CNS Tissue Concentration of Pooled NAD+/NADH [ Time Frame: At 12 Weeks ]
    Mean change in average CNS concentration of pooled NAD+/NADH [mmol/kg] by treatment group

  4. Mean Change in 31P-MRS Bioenergetic Metabolite CNS Tissue Concentration of Phosphocreatine (PCr) [ Time Frame: At 12 Weeks ]
    Mean change in average CNS concentration of PCr [mmol/kg] by treatment group

  5. Mean Change in 31P-MRS Bioenergetic Metabolite CNS Tissue Concentration of Intracellular Inorganic Phosphate (Pi(in)) [ Time Frame: At 12 Weeks ]
    Mean change in average CNS concentration of Pi(in) [mmol/kg] by treatment group

  6. Mean Change in 31P-MRS Bioenergetic Metabolite CNS Tissue Concentration of Extracellular Inorganic Phosphate (Pi(ex)) [ Time Frame: At 12 Weeks ]
    Mean change in average CNS concentration of Pi(ex) [mmol/kg] by treatment group

  7. Mean Change in 31P-MRS Bioenergetic Metabolite CNS Tissue Concentration of Uridine Diphosphate Glucose (UDPG) [ Time Frame: At 12 Weeks ]
    Mean change in average CNS concentration of UDPG [mmol/kg] by treatment group

  8. Mean Change in 31P-MRS Membrane Component Tissue Concentration of Phosphoethanolamine (PE) [ Time Frame: At 12 Weeks ]
    Mean change in average CNS concentration of PE [mmol/kg] by treatment group

  9. Mean Change in 31P-MRS Membrane Component CNS Tissue Concentration of Phosphocholine (PC) [ Time Frame: At 12 Weeks ]
    Mean change in average CNS concentration of PC [mmol/kg] by treatment group

  10. Mean Change in 31P-MRS Membrane Component CNS Tissue Concentration of glycerophosphoethanolamine (GPE) [ Time Frame: At 12 Weeks ]
    Mean change in average CNS concentration of GPE [mmol/kg] by treatment group

  11. Mean Change in 31P-MRS Membrane Component CNS Tissue Concentration of Glycerophosphocholine (GPC) [ Time Frame: At 12 Weeks ]
    Mean change in average CNS concentration of GPC [mmol/kg] by treatment group

  12. Mean Change in Multiple Sclerosis Functional Composite (MSFC) [ Time Frame: At 12 Weeks ]

    Mean change in Multiple Sclerosis Functional Composite (MSFC) by treatment group from Baseline to Week 12.

    The MSFC is a composite score generated by comparing the average results from three assessment on an individual basis to the population mean at the Baseline Visit. The MSFC includes the timed 25 foot walk test, the 9-hole peg test, and the paced auditory serial additional test.


  13. Mean Change in Symbol Digit Modality Test (SDMT) [ Time Frame: At 12 Weeks ]
    Mean change in Symbol Digit Modality Test (SDMT) by treatment group from Baseline to Week 12

  14. Mean Change in Optical Coherence Tomography (OCT) Retinal Layers [ Time Frame: At 12 Weeks ]
    Mean change in Optical Coherence Tomography (OCT) retinal layers by macular scan of Ganglion Cell + inner plexiform layer (GCIPL), Outer nuclear layer (ONL) and Inner nuclear layer (INL)

  15. Mean Change in Optical Coherence Tomography (OCT) Retinal Nerve Fiber Layer [ Time Frame: At 12 Weeks ]
    Mean change in Retinal Nerve Fiber Layer by Peripapillary Scan (pRNFL)

  16. Mean Change in Myelin Volume Fraction (MVF) [ Time Frame: At 12 Weeks ]
    Mean change in Myelin volume fraction (MVF) in baseline lesions and in normal appearing white matter (NAWM).

  17. Mean Change in Restricted Volume Fraction (F_R) [ Time Frame: At 12 Weeks ]
    Mean Change in Restricted Volume Fraction (F_R) in baseline lesions and in normal appearing white matter (NAWM).

  18. Mean Change in CSF Volume Fraction (F_CSF) [ Time Frame: At 12 Weeks ]
    Mean change in CSF Volume Fraction (F_CSF) between Baseline and Week 12 MRI

  19. Mean Change in Axonal Volume Fraction (AVF) [ Time Frame: At 12 Weeks ]
    Mean Change in Axonal Volume Fraction (AVF) in baseline lesions and in normal appearing white matter (NAWM).

  20. Mean Change in G-Ratio [ Time Frame: At 12 Weeks ]
    Mean change in g-ratio in baseline lesion and in normal appearing white matter (NAWM) represented as an aggregate measure calculated on a per-voxel basis

  21. Mean Change in G-Ration Susceptibility [ Time Frame: At 12 Weeks ]
    Mean change in the g-ratio susceptibility (ppm) in baseline lesion and in normal appearing white matter (NAWM).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 (inclusive) of age at Baseline.
  2. Clinical diagnosis of Multiple Sclerosis (MS) who have had Relapsing MS (RMS) no longer than 15 years from diagnosis.
  3. Stable treatment with natalizumab for at least the prior six (6) months.
  4. Stable disease activity over the prior six (6) months.
  5. All hematological parameters and biochemical parameters deemed stable or transient in nature.
  6. Able to understand and give written informed consent.

Exclusion Criteria:

  1. Patients with a clinical relapse requiring systemic steroid treatment within the prior six (6) months.
  2. Patients treated with any other MS therapy other than natalizumab; or treated with clemastine fumarate.
  3. Patients with a history of significant other major medical condition that may interfere with the conduct of the study or interpretation of the study results.
  4. Patients who may have difficulty complying with the protocol and/or study procedures.
  5. Patient with clinically significant abnormalities in hematology, blood chemistry, ECG, or physical examination not resolved by the Baseline visit which according to Investigator can interfere with study participation.
  6. 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 109 per liter) or eosinophilia (absolute eosinophil count of ≥500 eosinophils per microliter).
  7. Patients with a prior history of, or positive serological assay for the presence of HIV infection, or laboratory evidence of active or chronic infection with hepatitis C (HCV) or hepatitis B (HBV).
  8. Patients participating in any other investigational drug trial or using an investigational drug (within 12 weeks prior to screening and thereafter)
  9. Positive screen for drugs of abuse or known alcohol abuse.
  10. Females who are pregnant, have a positive pregnancy test, are nursing, or who plan to get pregnant during the course of this clinical trial or within 6 months of the end of this trial.
  11. Women of child-bearing potential, or men, who are unwilling or unable to use accepted methods of birth control during the study and for 6 months following completion of study participation.
  12. Patients with implanted metal objects in their body that may be affected by an MRI procedure.
  13. Patients who are claustrophobic or otherwise unlikely to be able to complete the MRI scanning procedures.
  14. Patients with a history of gold allergy.
  15. 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.
  16. Any active ophthalmological cause for retinal damage other than MS or based on the Investigator's judgment any other ophthalmic diseases that would confound the study results or optical coherence tomography assessment.
  17. PRN use of stimulant medications including: amphetamine, dextroamphetamine, lisdexamfetamine, methylphenidate, or modafinil.

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): NCT03993171


Contacts
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Contact: Austin Rynders, RN (801) 676-9695 info@clene.com
Contact: Michael Hotchkin (801) 676-9695 info@clene.com

Locations
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United States, Texas
University of Texas Southwestern Recruiting
Dallas, Texas, United States, 75390
Contact: Benjamin Greenberg, MD    214-645-0563    Benjamin.Greenberg@UTSouthwestern.edu   
Sponsors and Collaborators
Clene Nanomedicine
University of Texas Southwestern Medical Center
Investigators
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Principal Investigator: Benjamin Greenberg, MD University of Texas Southwestern Medical Center
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Responsible Party: Clene Nanomedicine
ClinicalTrials.gov Identifier: NCT03993171    
Other Study ID Numbers: CNMAu8.207
First Posted: June 20, 2019    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 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:
neurodegeneration
gold
nanoparticle
NAD+
redox
31P-MRS
multiple sclerosis
magnetic resonance spectroscopy
nanocrystal
NADH
Additional relevant MeSH terms:
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Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases