Trial Outcomes & Findings for 31P-MRS Imaging to Assess the Effects of CNM-Au8 on Impaired Neuronal Redox State in Parkinson's Disease (NCT NCT03815916)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

13 participants

Primary outcome timeframe

Baseline to 12 Weeks

Results posted on

2024-05-16

Participant Flow

The study was a single-center open-label pilot, sequential group, investigator-blinded study of the CNS metabolic effects, safety, pharmacokinetics, and pharmacodynamics of CNM-Au8 in patients who had been diagnosed with Parkinson's Disease (PD) within three (3) years of Screening. Patients were screened over a 6-week period. Patients who met the inclusion criteria and none of the exclusion criteria were enrolled into the clinical study.

There was no washout or run-in period that occurred between ICF signing and IP initiation. Once the participant signed the ICF and was confirmed to be eligible for the study, they were randomized into the study and dosed with IP.

Participant milestones

Participant milestones
Measure	Active: 30mg CNM-Au8 All participants in this group were dosed with 30 mg CNM-Au8 once daily. CNM-Au8 is an aqueous suspension of clean surfaced faceted nanocrystals consisting of gold atoms self-organized into various geometrical shapes (hexagonal bi-pyramid, pentagonal bi-pyramid, tetrahedron, decahedron, planar spheroids). These highly pure gold nanocrystals are suspended in purified water buffered with sodium bicarbonate (NaHCO3) nominally concentrated to 0.25 mg/L (250 ppm) to achieve a 30 mg dose CNM-Au8. CNM-Au8 was administered orally in a total volume of 120 mL taken once daily from two single-unit sterile 60 mL HDPE containers.
Overall Study STARTED	13
Overall Study COMPLETED	13
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active: 30mg CNM-Au8 n=13 Participants All participants in this group were dosed with 30 mg CNM-Au8 once daily. CNM-Au8 is an aqueous suspension of clean surfaced faceted nanocrystals consisting of gold atoms self-organized into various geometrical shapes (hexagonal bi-pyramid, pentagonal bi-pyramid, tetrahedron, decahedron, planar spheroids). These highly pure gold nanocrystals are suspended in purified water buffered with sodium bicarbonate (NaHCO3) nominally concentrated to 0.25 mg/L (250 ppm) to achieve a 30 mg dose CNM-Au8. CNM-Au8 was administered orally in a total volume of 120 mL taken once daily from two single-unit sterile 60 mL HDPE containers.
Age, Continuous	65.7 years STANDARD_DEVIATION 7.60 • n=99 Participants
Sex: Female, Male Female	6 Participants n=99 Participants
Sex: Female, Male Male	7 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants
Race (NIH/OMB) White	12 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Height	172.6 cm STANDARD_DEVIATION 10.85 • n=99 Participants
Weight	75.6 kg STANDARD_DEVIATION 16.63 • n=99 Participants
BMI	25.3 kg/m^2 STANDARD_DEVIATION 4.67 • n=99 Participants
MMSE Score	28.8 Score STANDARD_DEVIATION 1.28 • n=99 Participants
Child bearing potential	0 Participants n=99 Participants

PRIMARY outcome

Timeframe: Baseline to 12 Weeks

Population: Intent to Treat Population (ITT): The Intent to Treat population consisted of all screened subjects who were assigned a treatment assignment number.

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.

Outcome measures

Outcome measures
Measure	Active: 30mg CNM-Au8 n=13 Participants All participants in this group were dosed with 30 mg CNM-Au8 once daily. CNM-Au8 is an aqueous suspension of clean surfaced faceted nanocrystals consisting of gold atoms self-organized into various geometrical shapes (hexagonal bi-pyramid, pentagonal bi-pyramid, tetrahedron, decahedron, planar spheroids). These highly pure gold nanocrystals are suspended in purified water buffered with sodium bicarbonate (NaHCO3) nominally concentrated to 0.25 mg/L (250 ppm) to achieve a 30 mg dose CNM-Au8. CNM-Au8 was administered orally in a total volume of 120 mL taken once daily from two single-unit sterile 60 mL HDPE containers.
31P-MRS Redox Ratio	0.3856 Change in 31P-MRS Redox Ratio Standard Deviation 0.79968

OTHER_PRE_SPECIFIED outcome

Timeframe: At 12 Week

Mean change in average CNS concentration of NAD+ \[mmol/kg\] by treatment group

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At 12 Week

Mean change in average CNS concentration of NADH \[% Fraction\] by treatment group

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At 12 Weeks

Mean change in average CNS concentration of pooled NAD+/NADH \[mmol/kg\] by treatment group

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At 12 Week

Mean change in average CNS concentration of ATP \[mmol/kg\] (as internal reference) by treatment group

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At 12 Week

Mean change in average CNS concentration of PCr \[mmol/kg\] by treatment group

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At 12 Week

Mean change in average CNS concentration of Pi(in) \[mmol/kg\] by treatment group

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At 12 Week

Mean change in average CNS concentration of Pi(ex) \[mmol/kg\] by treatment group

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At 12 Week

Mean change in average CNS concentration of UDPG \[mmol/kg\] by treatment group

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At 12 Weeks

Mean change in average CNS concentration of PE \[mmol/kg\] by treatment group

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At 12 Weeks

Mean change in average CNS concentration of PC \[mmol/kg\] by treatment group

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At 12 Weeks

Mean change in average CNS concentration of GPE \[mmol/kg\] by treatment group

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At 12 Weeks

Mean change in average CNS concentration of GPC \[mmol/kg\] by treatment group

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: at 12 weeks

Measured by APDM instrumented Timed up and go test.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: at 12 weeks

Measured by APDM Instrumented Postural Sway Test

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: at 12 weeks

Measured by APDM instrumented Walk Test

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: at 12 weeks

Using Clinician Global Impression Scale. Scale is rated from 1-7, with 1 representing Very much improved and 7 representing very much worse.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: at 12 weeks

Using Patient Global Impression Scale. Scale is rated from 1-7, with 1 representing very mush improved, and 7 representing very much worse.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: at 12 weeks

Using Unified Parkinson's Disease Rating Scale. The scale is based off of participants symptoms, with a lower value representing a being closer to no impairments.

Outcome measures

Outcome data not reported

Adverse Events

Active: 30mg CNM-Au8

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Active: 30mg CNM-Au8 n=13 participants at risk All participants in this group were dosed with 30 mg CNM-Au8 once daily. CNM-Au8 is an aqueous suspension of clean surfaced faceted nanocrystals consisting of gold atoms self-organized into various geometrical shapes (hexagonal bi-pyramid, pentagonal bi-pyramid, tetrahedron, decahedron, planar spheroids).
Infections and infestations Nasopharyngitis	23.1% 3/13 • Number of events 3 • Adverse events were collected from the time of the signing of the Informed Consent to 28 days after the last day of study drug administration, up to 30 weeks.
Infections and infestations Herpes Zoster	7.7% 1/13 • Number of events 1 • Adverse events were collected from the time of the signing of the Informed Consent to 28 days after the last day of study drug administration, up to 30 weeks.
Infections and infestations Sinusitis	7.7% 1/13 • Number of events 1 • Adverse events were collected from the time of the signing of the Informed Consent to 28 days after the last day of study drug administration, up to 30 weeks.
Respiratory, thoracic and mediastinal disorders Allergic Cough	7.7% 1/13 • Number of events 1 • Adverse events were collected from the time of the signing of the Informed Consent to 28 days after the last day of study drug administration, up to 30 weeks.
Respiratory, thoracic and mediastinal disorders Dyspnea	7.7% 1/13 • Number of events 1 • Adverse events were collected from the time of the signing of the Informed Consent to 28 days after the last day of study drug administration, up to 30 weeks.
Gastrointestinal disorders Constipation	7.7% 1/13 • Number of events 1 • Adverse events were collected from the time of the signing of the Informed Consent to 28 days after the last day of study drug administration, up to 30 weeks.
Musculoskeletal and connective tissue disorders Arthralgia	7.7% 1/13 • Number of events 1 • Adverse events were collected from the time of the signing of the Informed Consent to 28 days after the last day of study drug administration, up to 30 weeks.
Nervous system disorders Dizziness	7.7% 1/13 • Number of events 1 • Adverse events were collected from the time of the signing of the Informed Consent to 28 days after the last day of study drug administration, up to 30 weeks.
Nervous system disorders Psychomotor Hyperactivity	7.7% 1/13 • Number of events 1 • Adverse events were collected from the time of the signing of the Informed Consent to 28 days after the last day of study drug administration, up to 30 weeks.

Additional Information

Jeremy Evan, PA-C

Clene Nanomedicine

Phone: 5419086335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60