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

NCT03815916 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CNMAu8.202
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Parkinson's Disease

Keywords

neurodegeneration; gold; nanocrystal; NAD+; redox; 31P-MRS; Parkinson's Disease; magnetic resonance spectroscopy; nanoparticle; nanomedicine; NADH

Outcome Measures

Primary Outcomes (1)

• 31P-MRS Redox Ratio

  The change in 31P-MRS NAD+/NADH ratio was measured by a partial volume coil that images the parietal and occipital lobes as a single value with respect to the fraction (%) of the nicotinamide adenine dinucleotide (NAD) signal measured as either the oxidized (NAD+) or reduced form (NADH). The primary endpoint was the mean change from Baseline to Week 12 in the ratio of NAD+ to NADH (NAD+/NADH) in the Intent to Treat population. A paired t-test was used to analyze the mean change from baseline.

  Baseline to 12 Weeks

Other Outcomes (18)

• Mean Change in 31P-MRS Bioenergetic Metabolite CNS Tissue Concentration of NAD+

  At 12 Week

• Mean Change in 31P-MRS Bioenergetic Metabolite CNS Tissue Concentration of NADH

  At 12 Week

• Mean Change in 31P-MRS Bioenergetic Metabolite CNS Tissue Concentration of Pooled NAD+/NADH

  At 12 Weeks

Study Arms (4)

7.5mg CNM-Au8

EXPERIMENTAL

7.5mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water

Drug: Gold Nanocrystals

15mg CNM-Au8

EXPERIMENTAL

15mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water

Drug: Gold Nanocrystals

30mg CNM-Au8

EXPERIMENTAL

30mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water

Drug: Gold Nanocrystals

60mg CNM-Au8

EXPERIMENTAL

60mg suspension of clean-surfaced, faceted, gold nanocrystals in 120ml of sodium bicarbonate buffered water

Drug: Gold Nanocrystals

Interventions

Gold Nanocrystals DRUG

CNM-Au8 is a dark red/purple-colored liquid formulation consisting of a stable suspension of faceted clean surfaced elemental gold nanocrystals in buffered deionized water with a concentration of up to 0.5 mg/mL of gold. The formulation is buffered by sodium bicarbonate present at a concentration of 0.546 mg/mL. There are no other excipients. The drug product is formulated to be taken orally and will be provided in single dose HDPE containers. The study doses vary by the concentration of gold nanocrystals per milliliter in a volume of 60 mL.

Also known as: CNM-Au8

15mg CNM-Au8; 30mg CNM-Au8; 60mg CNM-Au8; 7.5mg CNM-Au8

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and give written informed consent and follow study procedures.
• Male or female, aged 30 - 80 years or age (inclusive) at the time of PD diagnosis.
• PD subjects will be recruited in accordance with the MDS Clinical Diagnostic Criteria for
• PD:
• Parkinsonism present (bradykinesia + either rest tremor or rigidity)
• 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
• Duration of PD since diagnosis is \</= 3 years (inclusive)
• Modified Hoehn and Yahr stage \</= 3
• Treatment with dopaminergic therapy for at least 12-weeks and with no change in current medications within the prior 6-weeks

You may not qualify if:

• Atypical parkinsonism, including that due to drugs, metabolic disorders, encephalitis, cerebrovascular disease, normal pressure hydrocephalus, or other neurodegenerative disease.
• The presence of any of the following:
• Unequivocal cerebellar abnormalities
• Downward vertical gaze limitation or slowing of downward saccades
• Diagnosis of behavioral variant frontotemporal dementia or primary progressive aphasia
• Parkinsonian features restricted to the lower limbs for \> 3 years
• Treatment with dopamine blockers or depleters in a time course consistent with drug-induced parkinsonism
• Absence of an observable response to high dose levodopa despite moderate disease severity
• Expert considers a diagnosis of alternative syndrome more likely than PD
• Rapid progression of gait impairment requiring wheelchair within 5 years of onset
• Complete absence of progression of motor symptoms over 3 years unless due to treatment
• Early bulbar dysfunction within the first 5 years since diagnosis
• Inspiratory respiratory dysfunction (stridor or frequent sighs)
• Severe autonomic failure in the first 5 years
• Recurrent falls (\>1 per year) because of impaired balance in the first 3 years

Sponsors & Collaborators

• Clene Nanomedicine: lead
• University of Texas Southwestern Medical Center: collaborator

Study Sites (1)

UT Southwestern

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Parkinson Disease; Nerve Degeneration

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Only 13 participants were enrolled due to difficulties with recruitment that was further complicated by the COVID-19 pandemic.

Results Point of Contact

• Title: Jeremy Evan, PA-C
• Organization: Clene Nanomedicine

jeremy@clene.com

5419086335

Study Officials

• Richard Dewey, MD

  UT Southwestern

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Research participants and site personnel are not masked to study drug, but will be blinded to study dose for each cohort (single-blinded).
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open Label, Investigator Blinded, Sequential Cohort (max of 2 cohorts amongst the possible 4 interventions)

Study Record Dates

• First Submitted: January 18, 2019
• First Posted: January 24, 2019
• Study Start: December 19, 2019
• Primary Completion: June 7, 2021
• Study Completion: June 7, 2021
• Last Updated: May 16, 2024
• Results First Posted: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)