A phase 2 study to evaluate the effect of small gold particles on healing eyesight in patients with Relapsing Multiple Sclerosis
Type of Study/Intervention
Form of MS
Full trial title
VISIONARY-MS: A Phase 2, Randomized, Double-Blind, Parallel Group, Placebo Controlled Study for the Treatment of Visual Pathway Deficits In Chronic Optic Neuropathy to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of CNM-Au8 For Remyelination In Stable Relapsing Multiple Sclerosis (RMS)
The objective of this trial is to assess the efficacy and safety of the study drug CNMAu8 as a remyelinating treatment for vision-impairing MS lesions in participants who have RRMS. The primary endpoint is the change in remyelination measured after 24 weeks of treatment.
The trial will be conducted in up to 25 centres across Australia, New Zealand, Canada and the United States, with Australia being the main recruiting country. It is estimated the blinded study period will be approximately 52 weeks. Approximately 150 patients will be randomized in a ratio of 1:1:1 to receive either one of two doses of study drug or a matched placebo. Subjects will take a single oral dose daily and be on treatment for a minimum of 24 weeks and up to a maximum of 48 weeks, Subjects will be 18 to 50 years of age and have given informed consent prior to any study assessments and treatment. Subjects must be able to undergo planned procedures and may need to be at study centres from 1 to 6 hours.
• At least 18 years of age and up to 55 years (inclusive) of age at Screening
• Clinical diagnosis of Multiple Sclerosis (MS) (meeting McDonald criteria, 2010) who have had RMS no longer than 15 years from diagnosis.
• 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.
o 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 between 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.
o 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.
• Mean Retinal Nerve Fiber Layer (RNFL) thickness > 70μm in both eyes.
• Stable disease activity based on the Investigator’s judgment over the prior 6 months.
• All haematological parameters and biochemical parameters that fall outside the Within Normal Limits range must be assessed as Not Clinically Significant (NCS) and deemed stable or transient in nature.
• Able to understand and give written informed consent.
• History of AQP4, MOG Ab(+) status, or ≥ 3 segments lesion in the spinal cord.
• Any diagnosis other than RMS that could explain the patient’s signs and symptoms.
• An acute optic neuritis episode within the prior 6 months
• Clinical relapse requiring systemic steroid treatment within the prior 3 months (pre-treatment with systemic steroids during administration of disease modifying therapies (DMT) may be allowed after discussion with the Sponsor’s Medical Monitor but must not be administered within 30 days of a planned VEP or MRI assessment).
• Unstable treatment with a DMT defined as a treatment change within the prior 3-months unless due to intolerability.
• Current treatment with immunosuppressive or immunomodulatory therapy other than those approved for the treatment of MS.
• Any treatment with drugs known or suspected of producing retinal or optic nerve toxicity including hydroxychloroquine, chloroquine, clofazimine, vigabatrin, or ethambutol.
• Any history of 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);
• Severe refractive defects: refractive errors (–6 dioptres to +6 dioptres or more in either eye, or axial eye length >26 mm), hypermetropia (> 6 dioptres; cylinder > 3 dioptres); or based on the investigator’s judgment any other ophthalmic diseases that would confound the study results or assessment of VEPs, high contrast Best Corrected Visual Acuity (BCVA), Low Contrast Letter Acuity (LCLA), or Optical Coherence Tomography (OCT).
• History of diabetic retinopathy or a previous diagnosis of Diabetes Mellitus or history of prior impaired fasting glucose ≥126 mg/dL (or ≥ 200 mg/dL after oral glucose tolerance test).
• History of human immunodeficiency virus (HIV), hepatitis C (HepC) virus antibody, or hepatitis B (HepB) virus antibody without history of previous HepB vaccination
• History of gold allergy.
• Patients taking stimulant medications (including: amphetamine, dextroamphetamine, lisdexamfetamine, methylphenidate, or modafinil who have not been on a stable dose for ≥30 days (changes in dose will not be allowed during the course of the trial).
• Patients taking clemastine fumarate or 4-aminopyridine (fampridine) , or high-dose biotin (≥ 300 mg/day).
• Females who have a positive serum pregnancy test result at Screening or Baseline, or who are pregnant, breastfeeding, or planning to conceive during the study or within 180 days after study completion.
• History or evidence of substance abuse or alcohol abuse within 5-years prior to Screening, including alcoholism; or severe tobacco use (>1 pack/day).
• Clinical history of toxic neuropathy (e.g. secondary to treatment with ethambutol, isoniazid, linezolid, gentamycin, chloramphenicol, vincristine, or penicillamine).
• Current enrollment in any other drug or device treatment study within 3-months prior to Baseline. Current participation in an observational non-interventional study (i.e. no drug or device therapy) is not an exclusion criterion.
• Inability to undergo any planned study procedures such as LCLA, VEP or, MRI, including reduced renal clearance (screening: GFR < 45 mL/min),or OCT; history of severe hypersensitivity to gadolinium-DTPA, or reduced renal clearance (GFR must be ≥ 45 mL/min at Screening), claustrophobia; or inability to comply with study requirements based on Investigator judgment.
• 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.
• Based on the Investigator’s judgment, concurrent chronic or acute illness or unstable medical condition that may deteriorate that could confound the results of safety assessments, increase risk to the patient, or lead to difficulty complying with the protocol; including severe disc edema or hemorrhage, any clinically significant cardiac, endocrinological, hematological, hepatic, immunological, metabolic, urological, pulmonary, neurological (any progressive neurological disorder other than RRMS), dermatological, psychiatric (any untreated or unstable psychiatric disease including depression, bipolar and psychosis), renal, severe allergic or anaphylactic reactions, autoimmune or other major confounding disease.
• 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.
• 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.
Anticipated start date
Marinda Taha: firstname.lastname@example.org
T: +61 2 9351 0704
Clinical Trials Manager, MS Clinical Trials, Brain & Mind Centre, THE UNIVERSITY OF SYDNEY
Nicole Lingard: Nicole.Lingard@health.nsw.gov.au
T: +61 2 4042 0310
Clinical Trials Coordinator
John Hunter Hospital
Belinda Bardsley: email@example.com
T: +613 9496 3705
N-CRESS Manager, Austin Health
Janene Richards: firstname.lastname@example.org
T: +61 3 99038652
Clinical Research Coordinator, Alfred Health
Wendy Ockendon: email@example.com
T: +61 7 3176 9459
MS Nurse/Research Co-ordinator Princess Alexandra Hospital
Vanessa Maxwell: Vanessa.Maxwell@sa.gov.au
T: +61 8 8282 0631
Neurology Clinical Trials Coordinator and MS Nurse, Lyell McEwin Hospital
Angela McKechnie: firstname.lastname@example.org
T: +61 3 6226 4324
Clinical Trial Coordinator, Menzies Institute for Medical Research
For further details visit here:
19 Nov 2020