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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04098406




Registration number
NCT04098406
Ethics application status
Date submitted
19/09/2019
Date registered
23/09/2019
Date last updated
18/01/2020

Titles & IDs
Public title
Therapeutic Nanocatalysis to Slow Disease Progression of Amyotrophic Lateral Sclerosis (ALS)
Scientific title
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study in Early Symptomatic Amyotrophic Lateral Sclerosis Patients on Stable Background Therapy to Assess Bioenergetic Catalysis With CNM-Au8 to Slow Disease Progression in ALS.
Secondary ID [1] 0 0
CNMAu8.205
Universal Trial Number (UTN)
Trial acronym
RESCUE-ALS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis 0 0
Condition category
Condition code
Neurological 0 0 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - CNM-Au8
Treatment: Drugs - Placebo

Placebo Comparator: Placebo - The matched placebo to be used in this study will consist of water, sodium bicarbonate, and food coloring to match volume and color of the experimental treatment

Experimental: 30 mg CNM-Au8 - 30mg suspension of clean-surfaced, faceted, gold nanocrystals in 60ml of sodium bicarbonate buffered water


Treatment: Drugs: CNM-Au8
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.

Treatment: Drugs: Placebo
Placebo is liquid with identical color and taste

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean change in the average difference between active treatment and placebo from baseline for MUNIX (4) score. - The Motor Unit Number Index (MUNIX) is quantitative neurophysiological method that reflects loss of motor neurons in ALS. This will be measured via electromyography, the mean MUNIX values of the Abductor Digiti Minimi, Abductor Pollicis Brevis, Biceps Brachii, and Tibialis Anterior.
Timepoint [1] 0 0
36 weeks
Secondary outcome [1] 0 0
Mean change in the average difference between active treatment and placebo from Baseline as measured by MScanFit MUNE of the Abductor Pollicus Brevis. - The Motor Unit Number Estimation (MUNE) with compound muscle action potential (MScan) is a non-invasive electrophysiologic method to estimate the number of functioning motor units in a muscle.
Timepoint [1] 0 0
36 weeks
Secondary outcome [2] 0 0
Mean change in the average difference between active treatment and placebo from Baseline for the MUSIXscore(4). - The Motor Unit Size Index (MUSIX) will be reviewed via electormyography for the Abductor Pollicus Brevis (APB), Abductor Digiti Minimi (ADM), Biceps Brachii (BB), and Tibialis Anterior (TA). The relative motor neuron size at baseline will be averaged and the percent change from this baseline average will be calculated at week 36.
Timepoint [2] 0 0
36 weeks
Secondary outcome [3] 0 0
Mean change in the average difference between active treatment and placebo from Baseline for the Neurophysiological Index (NPI) of the ADM. - NPI is a method to quantify peripheral disease burden in ALS. NPI is defined as the ulnar nerve (ADM [CMAP peak amplitude] / ADM [distal motor latency]) x (ADM [f-wave %]).
Timepoint [3] 0 0
36 weeks
Secondary outcome [4] 0 0
Mean change in the average difference between active treatment and placebo from Baseline for the Split Hand Index (SI). - The SI is an early clinical feature that is used as a neurophysiological biomarker for evaluating ALS. The SI is derived by multiplying the compound muscle action potential (CMAP) amplitude over the APB by the CMAP amplitude of the First Distal Interosseous (FDI) muscle and dividing this product by the CMAP amplitude of the ADM.
Timepoint [4] 0 0
36 weeks

Eligibility
Key inclusion criteria
1. Able to understand and give written informed consent.

2. Male or female patients aged 40 years or greater (inclusive) and less than 80 years of
age at the time of ALS diagnosis.

3. 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).

4. For patients taking riluzole, stable dosing of riluzole over the prior 30-days from
Screening.

5. At the time of Screening either disease duration less than or equal to 24-months from
symptom onset, or disese duration less than or equal to 12-months from diagnosis.

6. Based on the ENCALS prediction criteria (www.ENCALSsurvivalmodel.org):

1. Current disease duration = 75% of predicted duration

2. Predicted 3-month risk of survival at the time of screening = 90%

3. Predicted 24-month risk of survival at the time of screening = 85%

7. Forced vital capacity (FVC) 60% of predicted value as adjusted for gender, height, and
age at the Screening Visit.

8. Patient who has established care with a neurologist at one of the specialised 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
organisation) they must be willing to transfer care to the neurologist participating
in the study.
Minimum age
40 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. At Screening patients who utilize, or in the Investigator's judgment will be
imminently dependent upon:

1. Non-invasive ventilation > 22 hours per day, or

2. Tracheostomy Note: If the patient requires non-invasive ventilation
post-randomisation, they will be allowed to continue in the study.

2. Patients with Familial ALS (e.g., 2 or more family members with ALS or motor neuron
disease)

3. 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.

4. 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.

5. Patient with a history of significant other major medical conditions based on the
Investigator's judgment.

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

7. 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.

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 10^9 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. 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.

11. Females of child-bearing potential, or men, who are unwilling or unable to use
accepted methods of birth control.

12. Active inflammatory condition or autoimmune disorder.

13. Positive screen for drugs of abuse.

14. History of gold allergy.

15. 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
University of Sydney Brain and Mind Centre - Sydney
Recruitment hospital [2] 0 0
Westmead Hospital - Sydney
Recruitment postcode(s) [1] 0 0
2050 - Sydney
Recruitment postcode(s) [2] 0 0
2145 - Sydney

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Clene Nanomedicine
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Clene Australia Pty Ltd
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The objective of this trial is 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 is the mean
change in the average difference between active treatment and placebo from Baseline through
Week 36 for the MUNIX score(4).
Trial website
https://clinicaltrials.gov/show/NCT04098406
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Parvarthi Menon, PhD, MD, MBBS
Address 0 0
Westmead Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Robert Glanzman, MD
Address 0 0
Country 0 0
Phone 0 0
801-676-9695
Fax 0 0
Email 0 0
info@clene.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04098406