31P-MRS Imaging to Assess the Effects of CNM-Au8 on Impaired Neuronal Redox State in Amyotrophic Lateral Sclerosis (REPAIR-ALS)

NCT03843710 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: CNMAu8.203
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

REPAIR-ALS 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 Amyotrophic Lateral Sclerosis (ALS) within twelve (12) months 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

Amyotrophic Lateral Sclerosis

Keywords

Neurodegeneration; gold; nanocrystal; NAD+; NADH; Redox; Redox Ratio; ALS; Amyotrophic Lateral Sclerosis; 31P-MRS; MRS; magnetic resonance spectroscopy; nanoparticle; nanomedicine

Outcome Measures

Primary Outcomes (1)

• Change in 31P-MRS Redox Ratio (NAD+/NADH)

  Mean change in average NAD+/NADH measured brain Redox Ratio by treatment group

  At 12 Weeks

Other Outcomes (11)

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

  At 12 Weeks

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

  At 12 Weeks

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

  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: 35 Years - 75 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.
• Male or female patients aged 35 years or greater (inclusive) and less than 75 years of age at the time of ALS diagnosis.
• Patients with a confirmed ALS diagnosis: "definite ALS" or "probable ALS" or "possible" diagnostic criteria per the revised El Escorial Criteria as determined by a neurologist subspecializing in ALS (e.g., the Principal Investigator by study site).
• Stable background therapy (e.g., stable dosing of riluzole within the prior 6-weeks) per Investigator discretion.
• At the time of Screening disease duration less than or equal to 24-months from symptom onset OR within 12-moths of a confirmed ALS diagnosis.
• Forced vital capacity (FVC) \>/= 60% of predicted value as adjusted for gender, height, and age at the Screening Visit.
• Patients who are ambulatory (e.g., normal ambulation, early ambulation difficulties, or walks with assistance) on the ALSFRS-R scale.

You may not qualify if:

• At Screening patients who utilize, or in the Investigator's judgment will be imminently dependent upon during the course of this study:
• Non-invasive ventilation
• Gastrostomy (e.g., use of percutaneous endoscopic gastrostomy tube)
• Use of wheel chair
• Patient who have previously undergone tracheostomy.
• Patient with a history of significant other major medical condition based on the Investigator's judgment.
• Based on the investigator's judgment, patients who may have difficulty complying with the protocol and/or study procedures.
• Patient with clinically significant abnormalities in hematology, blood chemistry, ECG, or physical examination not resolved by the Baseline visit which according to Investigator can interfere with study participation.
• Patient participating in any other investigational drug trial or using investigational drug (within 12 weeks prior to screening and thereafter)
• Females who are pregnant or nursing or who plan to get pregnant during the course of this clinical trial or within 6 months of the end of this trial.
• Positive screen for drugs of abuse or known alcohol abuse.
• Women of child-bearing potential, or men, who are unwilling or unable to use accepted methods of birth control during the study or for 6 months following completion of study participation.
• Women with a positive pregnancy test, are lactating, or are planning to become pregnant during the study.
• Patients with implanted metal objects in their body that may be affected by an MRI procedure.
• Patients who are claustrophobic or otherwise unlikely to be able to complete the MRI scanning procedures.

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

Amyotrophic Lateral Sclerosis; Nerve Degeneration

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jeffery Elliott, MD

  UT Southwestern

  PRINCIPAL INVESTIGATOR

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: February 14, 2019
• First Posted: February 18, 2019
• Study Start: March 1, 2020
• Primary Completion: February 1, 2022
• Study Completion: March 1, 2022
• Last Updated: April 3, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)