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
5. Stable disease activity based on the Investigator's judgment over the prior three
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
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 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).
10. Patients participating in any other investigational drug trial or using an
investigational drug (within 12 weeks prior to screening and thereafter).
11. Positive screen for drugs of abuse or known alcohol abuse.
12. 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.
13. 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.
14. Patients with implanted metal objects in their body that may be affected by an MRI
procedure.
15. Patients who are claustrophobic or otherwise unlikely to be able to complete the MRI
scanning procedures.
16. Patients with a history of gold allergy.
17. 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.
