Clinical trial NCT04626921: A Multi-Center, Open-Label Long-Term Extension Study of CNM-Au8 In Patients With Stable Relapsing Multiple Sclerosis
Official title: VISIONARY-MS LTE: A Multi-Center, Open-Label Long-Term Extension Study Assessing the Safety, Efficacy, Tolerability, and Pharmacokinetics of CNM-Au8 In Patients With Stable Relapsing Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Relapsing Multiple Sclerosis
Keywords: MS
RMS
Multiple Sclerosis
Demyelination
Remyelination
Optic Neuropathy
Optic Neuritis
Gold
Nanocrystal
Multifocal VEP
Full Field VEP
Low contrast letter acuity
Lead sponsor: Clene Nanomedicine
Sponsor class: INDUSTRY
Collaborators: name: George Clinical
First posted: 2020-11-13
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-Label, Long-Term Extension.
Primary purpose: TREATMENT

Brief summary: Open-label, long-term extension study available to participants who have completed CNMAu8.201.

Detailed description: This open-label, long-term extension study is only available to participants who have completed CNMAu8.201 (VISIONARY-MS). The Week 48/End-of-Study Visit for study CNMAu8.201 (VISIONARY-MS) will serve to establish the Baseline for electrophysiological, functional, morphological vision testing, as well as the neurological and outcome assessments. Participants will receive open-label CNM-Au8 throughout the study. All participants will receive a daily dose of 30 mg CNM-Au8 for the entire open-label, long-term extension study. The dose for participants may be adjusted once efficacy and safety data from study CNMAu8.201 becomes available, which may occur after participants have already started this study. Based upon a review of data and Sponsor or PI recommendation, this open-label, long-term extension study may be discontinued once each participant reaches her/his 48-week visit.

Eligibility criteria: Inclusion Criteria:

* Participants must have completed study CNMAu8.201.
* Able to understand and give written informed consent.

Exclusion Criteria:

* Lack of treatment compliance during participation in the CNMAu8.201 (VISIONARY-MS) study.
* Positive pregnancy test.
* 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.
* Based on the Investigator's judgment, any concurrent chronic or acute illness or unstable medical condition that could confound the results of safety assessments, increase risk to the participant, or lead to difficulty complying with the protocol; any untreated or unstable psychiatric disease including depression, bipolar and psychosis.
* Participant is considered a suicide risk in the opinion of the Investigator, has previously made a suicide attempt, or is currently demonstrating active suicidal ideation.

Following clinical and serology sample analysis conducted at the end-of-study visit for CNMAu8.201 (VISIONARY-MS), participants may be removed from this long term extension study if any of the following criteria are met, at the discretion of the Medical Monitor and/or Sponsor's Medical Representative:

* Positive serology for viral hepatitis B and/or C and/or human immunodeficiency virus (HIV).
* Abnormal liver function tests (aspartate aminotransferase \[ASAT\] or alanine aminotransferase \[ALAT\] \> 2x upper limit of normal range (ULN) or total bilirubin \> 2x ULN or alkaline phosphatase (AP) \> 3x ULN).
* Participants with clinically significant hepatic or renal dysfunction or clinical laboratory findings that would limit the interpretability of change in liver or kidney function (e.g., glomerular filtration rate \< 40 mL/min \[based on creatinine clearance according to Cockcroft-Gault equation\]), or those with low platelet counts (\<150 x 109 per liter) or eosinophilia (absolute eosinophil count of ≥500 eosinophils per microliter) at the EOS visit for CNMAu8.201 (Visionary-MS).

Primary outcomes:
measure: Change in Best-Corrected Low-Contrast Letter Acuity score.
timeFrame: 2 years
measure: Incidence of treatment-emergent AEs throughout the study.
timeFrame: 2 years
Secondary outcomes:
measure: Measure of neurological function assessed by a functional composite responder analysis.
timeFrame: 2 years
Other outcomes:
measure: Change in best corrected Low-Contrast Letter Acuity score for total number of correct letter.
timeFrame: 2 years
measure: Change in Best Corrected High Contrast Visual Acuity
timeFrame: 2 years
measure: VEP latency for Multi-Focal visual evoked potential.
timeFrame: 2 years
measure: VEP latency for Full Field Visual Evoked Potential
timeFrame: 2 years
measure: VEP Amplitude for Multi-Focal Visual Evoked Potential
timeFrame: 2 years
measure: VEP Amplitude for Full Field Visual Evoked Potential
timeFrame: 2 years
measure: OCT of the Retinal Nerve Fiber Layer (RNFL) by Peripapillary Scan
timeFrame: 2 years
measure: OCT of the Retinal Layers by Macular Scan evaluating Ganglion cell and inner plexiform.
timeFrame: 2 years
measure: OCT of the Retinal Layers by Macular Scan evaluating Ganglion cell layer.
timeFrame: 2 years
measure: OCT of the Retinal Layers by Macular Scan evaluating Inner nuclear layer.
timeFrame: 2 years
measure: OCT of the Retinal Layers by Macular Scan evaluating outer nuclear layer.
timeFrame: 2 years
measure: MRI Evaluation of the Mean change in whole brain and OR T2 lesion volume.
timeFrame: 2 years
measure: MRI Evaluation of the Mean change in whole brain and optic radiation T1 hypo-intense lesion volume.
timeFrame: 2 years
measure: MRI Evaluation of the Proportion of Baseline Gd+ lesions converting to black holes.
timeFrame: 2 years
measure: MRI Evaluation of the Volume of Baseline Gd+ lesions converting to T1 hypointense lesions.
timeFrame: 2 years
measure: MRI Evaluation of the Mean percent whole brain volume change (PBVC) from baseline.
timeFrame: 2 years
measure: MRI Evaluation of the Mean Percent Cerebral Cortical Change from Baseline
timeFrame: 2 years
measure: MRI Evaluation of the Mean Percent Thalamic Volume Change from Baseline.
timeFrame: 2 years
measure: MRI Evaluation of the Mean Percent Deep Grey Nuclei Volume Change from Baseline.
timeFrame: 2 years
measure: MRI Evaluation of the Mean change in number of whole brain new/enlarging T2 lesion(s) from baseline.
timeFrame: 2 years
measure: Mean change in whole brain DTI/MTR from baseline.
timeFrame: 2 years
measure: Mean change in optic radiation lesional/non-lesional fibre DTI / MTR difference from Baseline (fiber based, individually reported for each baseline OR lesion).
timeFrame: 2 years
measure: Mean change in MWF from Baseline in the whole brain.
timeFrame: 2 years
Locations:
city: Camperdown
country: Australia
facility: Sydney Brain Mind Centre
state: New South Wales
city: New Lambton Heights
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Hobart
country: Australia
facility: Menzies Institute for Medical Research
state: TAZ
city: Melbourne
country: Australia
facility: The Alfred Centre Department of Neuroscience
state: Victoria
Study officials:
References: