Nanocrystalline Gold to Treat Remyelination Failure in Chronic Optic Neuropathy In Multiple Sclerosis

• Status: Recruiting
• Trial end date: 2022-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The objective of this trial is to assess the efficacy and safety of CNM-Au8 as a remyelinating treatment for vision-impairing MS lesions in participants who have chronic vision impairment as a result of Relapsing-Remitting Multiple Sclerosis. The primary endpoint is to assess the efficacy and safety of CNM-Au8 as a remyelinating therapy in patients with stable RMS. The secondary endpoint is Change in Functional Composite Responder Analysis Score from Baseline to Week 24.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Clene Nanomedicine
• Collaborator: Clene Australia Pty Ltd

Criteria

Inclusion Criteria:

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

2. Clinical diagnosis of Relapsing Multiple Sclerosis (meeting McDonald criteria, 2010) who have had RMS no longer than 15 years from diagnosis.

3. 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.

a. 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.

4. Best Corrected Low Contrast Letter Acuity (BC-LCLA) (by 2.5% Sloan Chart) must be 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.

a. 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.

5. Retinal Nerve Fiber Layer (RNFL) thickness ≥ 70 μm.

6. Stable disease activity based on the investigator's judgment over the previous 6 months.

7. All hematological 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.

8. Able to understand and give written informed consent.

Exclusion Criteria:

1. History of AQP4, MOG Ab(+) status, or ≥ 3 segments lesion in the spinal cord.

2. Any diagnosis other than RMS that could explain the patient's signs and symptoms.

3. An acute optic neuritis episode within the prior 6 months.

4. Clinical relapse requiring systemic steroid treatment within the prior 3 months (pre- treatment with systemic steroids during the 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).

5. Unstable treatment with a disease-modifying therapy (DMT) defined as a treatment change within prior 3-months unless due to intolerability.

6. Current treatment with immunosuppressive or immunomodulatory therapy other than those approved for the treatment of MS.

7. Any treatment with drugs known or suspected of producing retinal or optic nerve toxicity including hydroxychloroquine, chloroquine, clofazimine, vigabatrin, or ethambutol.

8. 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).

9. 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 investigators judgment any other ophthalmic diseases that would confound the study results or assessment of Visual Evoked Potential (VEPs), Best Corrected Visual Acuity (BCVA), Low Contrast Letter Acuity (LCLA), or Optical Coherence Tomography (OCT).

10. History 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).

11. History of human immunodeficiency virus (HIV), hepatitis C (HepC) virus antibody, or hepatitis B (HepB) virus antibody.

12. History of gold allergy.

13. Patients taking stimulant medications (including: amphetamine, dextroamphetamine, lisdexamfetamine, methylphenidate, or modafinil) who have not been on a stable dose greater than or equal to 30 days. Changes to dose will not be allowed during the course of the trial).

14. Patients taking clemastine fumarate, 4-aminopyridine (fampridine), or high dose Biotin (>300 mg/day).

15. 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.

16. History or evidence of substance abuse or alcohol abuse within 5 years prior to Screening, including alcoholism; or severe tobacco use (>1 pack/day).

17. Clinical history of toxic neuropathy (e.g., secondary to treatment with ethambutol, isoniazid, linezolid, gentamycin, chloramphenicol, vincristine, or penicillamine).

18. Current enrollment in any other drug or device treatment study within 3 months prior to Baseline. Participation in an observational non-interventional study (i.e., no drug or device therapy) is not an exclusion criterion.

19. Inability to undergo any planned study procedures such as LCLA, VEP, MRI, 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.

20. 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 10^9 per liter) or eosinophilia (absolute eosinophil count of ≥ 500 eosinophils per microliter) at Screening.

21. 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 diseases.

22. 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.

23. 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.