Therapeutic Nanocatalysis to Slow Disease Progression of Amyotrophic Lateral Sclerosis (ALS)

NCT04098406 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CNMAu8.205
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

Brief Summary

The objective of this trial was to assess the efficacy, safety, and PK/PD effects of CNM-Au8 as a disease-modifying agent for the treatment of ALS by utilizing electrophysiological measures to detect preservation of motor neuron function. The primary endpoint was the mean change in the average difference between active treatment and placebo from Baseline through Week 36 evaluated by electromyography.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Gold; Nanocrystal; electromyography; ALS; Nanoparticle

Outcome Measures

Primary Outcomes (1)

• Electromyography Measures of Disease Progression.

  The Motor Unit Number Index (MUNIX) is a quantitative neurophysiological measure that provides an index of the number of lower motor neurons supplying a muscle. It reflects the loss of motor neurons in patients with ALS. Mean change in the average difference between active treatment and placebo from Baseline through Week 36 for the MUNIXscore(4), which is the sum of the respective MUNIX values for the Abductor Digiti Minimi (ADM), Abductor Pollicis Brevis (APB), Biceps Brachii (BB), and Tibialis Anterior (TA). The average baseline summed values will be indexed to 100%. Changes will be calculated as the percent change from the Baseline index of 100%.

  36 weeks

Secondary Outcomes (2)

• Percentage Mean Change in the Average Difference Between Active Treatment and Placebo From Baseline for Respiratory Function as Measured by Forced Vital Capacity (FVC).

  36 weeks

• Mean Absolute Change of the Average Difference Between Active Treatment and Placebo From Baseline Through Week 36 for the MUNIXscore(4).

  36 weeks

Other Outcomes (14)

• Mean Change in the Average Difference Between Active Treatment and Placebo From Baseline Through Week 36 (Overall Difference at All Time Points) as Measured by MScanFit MUNE (Jacobsen et al., 2017) of the APB.

  36 weeks

• Mean Change in the Average Difference Between Active Treatment and Placebo From Baseline Through Week 36 for the MUSIXscore(4) (Neuwirth et al., 2015), Which is the Mean of the Respective MUSIX Values for the ADM, APB, BB, and TA.

  36 weeks

• Mean Change in the Average Difference Between Active Treatment and Placebo From Baseline for the Neurophysiological Index (NPI) of the ADM.

  36 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

The matched placebo used in this study consisted of water, sodium bicarbonate, and food coloring to match volume and color of the experimental treatment

Drug: Placebo

30 mg CNM-Au8

EXPERIMENTAL

30mg suspension of clean-surfaced, faceted, gold nanocrystals in 60ml of sodium bicarbonate buffered water

Drug: CNM-Au8

Interventions

CNM-Au8 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 nominal concentration of 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 60 mL HDPE containers.

30 mg CNM-Au8

Placebo DRUG

Placebo was liquid with identical color and taste

Placebo

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.
• Male or female patients aged 30 years or greater (inclusive) and less than 80 years of age at the time of Screening.
• Patients whose conditions are defined as possible or probable or definite ALS per the diagnostic criteria by Awaji-Shima criteria as determined by a neurologist sub- specialising in ALS (e.g., the Principal Investigator by study site).
• For patients taking riluzole, stable dosing of riluzole over the prior 30-days from Screening.
• At the time of Screening either disease duration less than or equal to 24-months from symptom onset, or disease duration less than or equal to 12-months from diagnosis.
• Forced vital capacity (FVC) 60% of predicted value as adjusted for gender, height, and age at the Screening Visit.
• Patient who has established care with a neurologist at one of the specialized ALS clinics involved in the study and will maintain this clinical care throughout the study. If a patient is referred from a third party (neurologist or a State based ALS organization) they must be willing to transfer care to the neurologist participating in the study.
• Participants must have completed the randomized placebo controlled Treatment Period without compliance issues
• Able to understand and give written informed consent to participant in the open-label extension.
• If referred from a third party (neurologist or a State based ALS organization), participant agrees to maintain transfer of care to a neurologist participating in the study.

You may not qualify if:

• Patients will be excluded from the study if they meet any of the following criteria:
• At Screening patients who utilize, or in the Investigator's judgment will be imminently dependent upon:
• Non-invasive ventilation \> 22 hours per day, or
• Tracheostomy Note: If the patient requires non-invasive ventilation postrandomisation, they will be allowed to continue in the study.
• Patients with Familial ALS (e.g., 2 or more family members with ALS or motor neuron disease)
• Patients with a history of carpal tunnel syndrome, polyneuropathy, or in the investigators judgement diseases that could induce polyneuropathy and interfere with electromyography (EMG) recordings.
• Patients with too severe atrophy of the Abductor Digiti Minimi (ADM), Abductor Pollicis Brevis (APB), Biceps Brachii (BB), or Tibialis Anterior (TA) muscles in the least clinically affected hand and leg, respectively, to allow for reliable EMG recordings.
• Patient with a history of significant other major medical conditions based on the Investigator's judgment.
• Based on the investigator's judgment, patients who may have difficulty complying with the protocol and/or any study procedures.
• Patient with clinically significant abnormalities in haematology, blood chemistry, ECG, or physical examination not resolved by the Baseline visit which according to Investigator can interfere with study participation.
• 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.
• 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.
• Females of child-bearing potential, or men, who are unwilling or unable to use accepted methods of birth control.
• Active inflammatory condition or autoimmune disorder.

Sponsors & Collaborators

• Clene Nanomedicine: lead
• Clene Australia Pty Ltd.: collaborator

Study Sites (2)

University of Sydney Brain and Mind Centre

Sydney, New South Wales, 2050, Australia

Location

Westmead Hospital

Sydney, New South Wales, 2145, Australia

Location

Related Publications (3)

• Vucic S, Menon P, Huynh W, Mahoney C, Ho KS, Hartford A, Rynders A, Evan J, Evan J, Ligozio S, Glanzman R, Hotchkin MT, Kiernan MC. Efficacy and safety of CNM-Au8 in amyotrophic lateral sclerosis (RESCUE-ALS study): a phase 2, randomised, double-blind, placebo-controlled trial and open label extension. EClinicalMedicine. 2023 Jun 8;60:102036. doi: 10.1016/j.eclinm.2023.102036. eCollection 2023 Jun.

  PMID: 37396808 RESULT

• Saha S, Tripathy S, Patra CR. Neuritogenic activity of metal nanoparticles. Nanomedicine (Lond). 2024 Feb;19(5):363-366. doi: 10.2217/nnm-2023-0297. Epub 2024 Jan 12. No abstract available.

  PMID: 38214170 DERIVED

• Vucic S, Kiernan MC, Menon P, Huynh W, Rynders A, Ho KS, Glanzman R, Hotchkin MT. Study protocol of RESCUE-ALS: A Phase 2, randomised, double-blind, placebo-controlled study in early symptomatic amyotrophic lateral sclerosis patients to assess bioenergetic catalysis with CNM-Au8 as a mechanism to slow disease progression. BMJ Open. 2021 Jan 11;11(1):e041479. doi: 10.1136/bmjopen-2020-041479.

  PMID: 33431491 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

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

Results Point of Contact

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

jeremy@clene.com

5419086335

Study Officials

• Parvarthi Menon, PhD, MD, MBBS

  Westmead Hospital

  PRINCIPAL INVESTIGATOR

• William Huynh, MD

  University of Sydney, Brain and Mind Centre

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The drug formulations were identical in appearance (size, shape, volume, color) and smell. The packaging and labeling were designed to maintain blinding to the Investigator's team and to patients. There are no visible differences between the active drug, and placebo dosing units
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: randomized, double-blind, parallel group, placebo-controlled study

Study Record Dates

• First Submitted: September 19, 2019
• First Posted: September 23, 2019
• Study Start: December 19, 2019
• Primary Completion: July 13, 2021
• Study Completion: July 13, 2021
• Last Updated: July 3, 2024
• Results First Posted: July 3, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2)