31P-MRS Imaging to Assess the Effects of CNM-Au8 on Impaired Neuronal Redox State in Multiple Sclerosis.

• Register: ClinicalTrials.gov
• Last refreshed on: 10 February 2025
• Main ID: NCT03993171
• Date of registration: 31/05/2019
• Prospective Registration: Yes
• Primary sponsor: Clene Nanomedicine
• Public title: 31P-MRS Imaging to Assess the Effects of CNM-Au8 on Impaired Neuronal Redox State in Multiple Sclerosis. REPAIR-MS
• Scientific 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.
• Date of first enrolment: December 19, 2019
• Target sample size: 30
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03993171
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Peter Sguigna, MD
• Affiliation: University of Texas Southwestern Medical Center

Key inclusion & exclusion criteria

Patients enrolled in Cohort 1 must meet the following Inclusion Criteria:

1. At least 18 years of age and up to 55 years (inclusive) of age at Screening.

2. Clinical diagnosis of Relapsing Multiple Sclerosis (RMS) (meeting McDonald criteria,
2017).

3. Diagnosis of MS no longer than 15 years prior to Screening.

4. Stable treatment with natalizumab, defined as a stable dose maintained at the
standard infusion interval of 28-days (±5 days) for at least the prior six (6)
months.

5. Stable disease activity based on the Investigator's judgment over the prior three
(3) months.

6. Any hematological parameters and/or biochemical parameters that fall outside the
Within Normal Limits range at Screening must be assessed as Not Clinically
Significant (NCS) and deemed stable or transient in nature.

7. Able to understand and give written informed consent.

Patients enrolled in Cohort 2 must meet the following Inclusion Criteria:

1. Male or female, aged 18 - 70 years or age (inclusive);

2. Diagnosis of primary progressive multiple sclerosis (PPMS) or nonactive secondary
progressive multiple sclerosis (SPMS), according to revised 2017 McDonald criteria
at the Screening visit;

3. EDSS score at the Screening visit of less than or equal to 6.5 (inclusive);

4. Participants must be taking either B-cell depleting therapy (e.g., ocrelizumab,
rituximab) or S1P modulator therapy (e.g., siponimod) with consistent stable dosing
for at least 48 weeks prior to the Screening visit;

5. Any hematological parameters and/or biochemical parameters that fall outside the
Within Normal Limits range at Screening must be assessed as Not Clinically
Significant (NCS) and deemed stable or transient in nature; and

6. Able to understand and give written informed consent.

Patients enrolled in Cohort 1 must meet the following Exclusion Criteria:

1. Patients with a clinical relapse requiring systemic steroid treatment within the
prior three (3) months.

2. Patients treated with any other MS therapy other than natalizumab; or treated with
clemastine fumarate.

3. Based on the Investigator's judgment, 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. Based on the Investigator's judgment, patients who may have difficulty complying
with the protocol and/or study procedures.

5. History of any clinically significant abnormality 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) at Screening.

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). Note, participants who have been vaccinated for HBV
and have detectable HB antibodies are not excluded unless positive for hepatitis
surface antigen (HBsAg).

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. Subjects with intermittent passive suicidal ideation are not necessarily
excluded based on the assessment of the Investigator.

16. Any active 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).

17. Severe refractive defects: refractive errors (-5 dioptres to +5 dioptres or more in
either eye or axial eye length >26 mm), hypermetropia (> 5 dioptres; cylinder > 3
dioptres); or based on the Investigator's judgment any other ophthalmic diseases
that might confound the study results or optical coherence tomography assessment.

18. PRN use of stimulant medications including: amphetamine, dextroamphetamine,
lisdexamfetamine, methylphenidate, or modafinil; however, stimulant medications,
taken on a consistent daily dose for at least 12-weeks are allowed. No changes in
the dose of any stimulant medications are allowed during the study.

Patients enrolled in Cohort 2 must meet the following Exclusion Criteria:

1. History of MS relapses or gadolinium-enhancing lesions seen on brain MRI scans
within the five (5) years prior to the Screening visit.

2. History of AQP4, MOG Ab(+) status, or documented = 3 contiguous segment lesion in
the spinal cord.

3. Any diagnosis other than PPMS or SPMS that could explain a participant's signs and
symptoms.

4. Participants taking any MS disease-modifying therapy other than Bcell depleting
therapy (e.g., ocrelizumab, rituximab) or S1P modulator therapy (e.g., siponimod),
or not taking disease modifying therapy.

5. Based on the Investigator's judgment, 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.

6. Based on the Investigator's judgment, patients who may have difficulty complying
with the protocol and/or study procedures.

7. History of any clinically significant abnormality in hematology, blood chemistry,
ECG, or physical examination not resolved by the Baseline visit which according to
Investigator can interfere with study participation.

8. 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) at
Screening.

9. Patients with a prior history of, or positive serological assay for the presence of
HIV infection, or


Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Sclerosis

Intervention(s)

Drug: gold nanocrystals

Primary Outcome(s)

The change from baseline to week 12 in CNS metabolic changes, based on 31P-MRS Redox Ratio. [Time Frame: At 12 Weeks]

Secondary ID(s)

CNMAu8.207

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

University of Texas Southwestern Medical Center