31P-MRS Imaging to Assess the Effects of CNM-Au8 on Impaired Neuronal Redox State in Parkinson's Disease

• Status: Recruiting
• Trial end date: 2021-07-01
• Target enrollment: 0
• Participant gender: All

Summary

REPAIR-PD is a single-center open label pilot, sequential group, investigator and patient blinded study to assess the CNS metabolic effects, safety, pharmacokinetics, and pharmacodynamics of CNM-Au8 in patients who have been diagnosed with Parkinson's Disease (PD) within three (3) years of Screening. The primary endpoint is the ratio of the oxidized to reduced form of nicotinamide adenine dinucleotide (NAD+:NADH) measured non-invasively by 31phosphorous magnetic resonance spectroscopy (31P-MRS).

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

Details

• Lead Sponsor: Clene Nanomedicine
• Collaborator: University of Texas Southwestern Medical Center

Criteria

Inclusion Criteria:

1. Able to understand and give written informed consent and follow study procedures.

2. Male or female, aged 30 - 80 years or age (inclusive) at the time of PD diagnosis.

3. PD subjects will be recruited in accordance with the MDS Clinical Diagnostic Criteria for

PD:

1. Parkinsonism present (bradykinesia + either rest tremor or rigidity)

2. 2 of the following 4 supportive criteria:

i. Clear and dramatic beneficial response to dopaminergic medication

ii. Presence of levodopa-induced dyskinesias

iii. Rest tremor of a limb

iv. Olfactory loss or cardiac sympathetic denervation seen on prior MIBG SPECT

4. Duration of PD since diagnosis is

5. Modified Hoehn and Yahr stage

6. Treatment with dopaminergic therapy for at least 12-weeks and with no change in current medications within the prior 6-weeks

Exclusion Criteria:

1. Atypical parkinsonism, including that due to drugs, metabolic disorders, encephalitis, cerebrovascular disease, normal pressure hydrocephalus, or other neurodegenerative disease.

2. The presence of any of the following:

1. Unequivocal cerebellar abnormalities

2. Downward vertical gaze limitation or slowing of downward saccades

3. Diagnosis of behavioral variant frontotemporal dementia or primary progressive aphasia

4. Parkinsonian features restricted to the lower limbs for > 3 years

5. Treatment with dopamine blockers or depleters in a time course consistent with drug-induced parkinsonism

6. Absence of an observable response to high dose levodopa despite moderate disease severity

7. Expert considers a diagnosis of alternative syndrome more likely than PD

8. Rapid progression of gait impairment requiring wheelchair within 5 years of onset

9. Complete absence of progression of motor symptoms over 3 years unless due to treatment

10. Early bulbar dysfunction within the first 5 years since diagnosis

11. Inspiratory respiratory dysfunction (stridor or frequent sighs)

12. Severe autonomic failure in the first 5 years

13. Recurrent falls (>1 per year) because of impaired balance in the first 3 years

14. Disproportionate dystonic anterocollis or hand contractures of hands or feet within 10 years

15. Absence of any of the common non-motor features of PD despite 5 years of disease

16. Otherwise unexplained pyramidal tract signs (weakness, hyperreflexia, or extensor toe signs)

17. Bilateral symmetric parkinsonism

3. Mini-Mental State Exammination (MMSE) score of less than 19.

4. Patient with a history of any clinically significant or unstable medical condition based on the Investigator's judgment.

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

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

7. Patient with clinically significant abnormalities in hematology, blood chemistry, ECG, or physical examination not resolved by the Baseline visit which according to Investigator may 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. Patient participating in any other investigational drug trial or using investigational drug (within 12 weeks prior to screening and thereafter)

10. Positive screen for drugs of abuse or known history of alcohol abuse.

11. Women of child-bearing potential, or men, who are unwilling or unable to use accepted methods of birth control for up to 6 months following study participation.

12. Women with a positive pregnancy test, are lactating, or are planning to become pregnant during the study or within 6 months of the end of this trial.

13. Patients with implanted metal objects in their body that may be affected by an MRI procedure.

14. Patients who are claustrophobic or otherwise unlikely to be able to complete the MRI scanning procedures.

15. History of allergy to gold in any form.

16. 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.