Therapeutic Nanocatalysis to Slow Disease Progression of Amyotrophic Lateral Sclerosis (ALS) (RESCUE-ALS)
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|ClinicalTrials.gov Identifier: NCT04098406|
Recruitment Status : Recruiting
First Posted : September 23, 2019
Last Update Posted : November 4, 2020
|Condition or disease||Intervention/treatment||Phase|
|Amyotrophic Lateral Sclerosis||Drug: CNM-Au8 Drug: Placebo||Phase 2|
Expanded Access : An investigational treatment associated with this study is available outside the clinical trial. More info ...
This is a multi-centre randomized, double-blind, parallel group, placebo-controlled study of the efficacy, safety, pharmacokinetics, and pharmacodynamics of CNM-Au8 in patients who are newly symptomatic within 24-months of Screening and with a clinically probable or possible or definite ALS diagnosis per the Awaji-Shima criteria.
Patients may be screened over up to a 6-week period. Patients who meet the inclusion criteria and none of the exclusionary criteria will be enrolled into the clinical study. Patients will be randomized 1:1 into one of two groups: either active treatment with CNM-Au8 30 mg or Placebo.
All patients will receive their randomized oral treatment daily over thirty-six (36) consecutive weeks during the Treatment Period.
There will be up to four study periods:
- Up to a six (6) week screening period (Screening Period);
- A thirty-six (36) week blinded randomized treatment period (Treatment Period);
- Up to a forty-eight (48) week optional open-label extension period (Open-Label Period);
- A four (4) week safety follow-up period following completion of either the Treatment or Open-Label period or in the case of Early Termination (Safety Follow-Up Period).
Per protocol, all patients will receive their blinded and randomized oral treatment daily over at least 36 consecutive weeks during the Treatment Period.
For those patients not transitioning into the optional OLE period, patients will complete a safety follow-up visit 4-weeks following study drug discontinuation.
An independent DSMB will be responsible for monitoring the safety of the study on a quarterly basis and ad hoc at the request of the DSMB or the Sponsor (e.g., in the event of unexpected SAEs) to review data throughout the Treatment Period. The DSMB may make recommendations on the conduct of the study, including study termination. Appropriate procedures will be detailed in a DSMB Charter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||42 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||randomized, double-blind, parallel group, placebo-controlled study|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||The drug formulations will be identical in appearance (size, shape, volume, color) and smell. The packaging and labeling will be 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|
|Official 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.|
|Actual Study Start Date :||December 19, 2019|
|Estimated Primary Completion Date :||July 2021|
|Estimated Study Completion Date :||August 2022|
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
Placebo is liquid with identical color and taste
Experimental: 30 mg CNM-Au8
30mg suspension of clean-surfaced, faceted, gold nanocrystals in 60ml of sodium bicarbonate buffered water
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.
- Electromyography measures of disease progression. [ Time Frame: 36 weeks ]Mean change in the average difference between active treatment and placebo from Baseline through Week 36 for the MUNIXscore(4), which is the mean 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 mean values will be indexed to 100%. Changes will be calculated as the percent change from the Baseline index of 100%.
- Mean change in the average difference between active treatment and placebo from Baseline as measured by MScanFit MUNE of the Abductor Pollicus Brevis. [ Time Frame: 36 weeks ]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.
- Mean change in the average difference between active treatment and placebo from Baseline for the MUSIXscore(4). [ Time Frame: 36 weeks ]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.
- Mean change in the average difference between active treatment and placebo from Baseline for the Neurophysiological Index (NPI) of the ADM. [ Time Frame: 36 weeks ]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 %]).
- Mean change in the average difference between active treatment and placebo from Baseline for the Split Hand Index (SI). [ Time Frame: 36 weeks ]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.
- Mean change between active treatment and placebo in the proportion of patients experiencing a > 6-point decline in the ALSFRS-R between active treatment and placebo. [ Time Frame: 36 weeks ]Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R)
- Mean change in average ALSFRS-R score [ Time Frame: 36 weeks ]The ALS Functional Rating Scale-Revised (ALSFRS-R) is a validated rating instrument for monitoring the progression of disability in patients with ALS. The revised version incorporates additional assessments of dyspnea, orthopnea, and the need for ventilatory support.
- Mean change in slope of the decline of the ALSFRS-R [ Time Frame: 36 weeks ]The ALS Functional Rating Scale-Revised (ALSFRS-R) is a validated rating instrument for monitoring the progression of disability in patients with ALS. The revised version incorporates additional assessments of dyspnea, orthopnea, and the need for ventilatory support.
- Mean change between active treatment and placebo for the Combined Assessment of Function and Survival (CAFS), a joint-rank analysis of function (ALSFRS-R) and overall survival [ Time Frame: 36 weeks ]CAFS and ALSFRS-R
- Mean change in the proportion of patients experiencing ALS clinical composite disease progression [ Time Frame: 36 weeks ]Disease progression defined as the occurrence of death, tracheostomy, use of non-invasive ventilatory respiratory support, insertion of a gastrostomy tube, or a 6-point drop in the ALSFRS-R score.
- Mean change in rate of disease progression defined as the average change in the Functional Survival (FS) score ([Max ALSFRS-R minus current ALSFRS-R score]/symptom duration in months) [ Time Frame: 36 weeks ]Change in FS score = (Max ALSFRS-R minus current ALSFRS-R score) divided by symptom duration in months.
- Mean change in the average difference between active treatment and placebo for respiratory function as measured by forced vital capacity (FVC) [ Time Frame: 36 weeks ]FVC - Forced Vital Capacity
- Mean change in average difference between active treatment and placebo for the ALSSQOL-Short Form questionnaire (ALSSQOL-SF) [ Time Frame: 36 weeks ]ALS Specific Quality of Life - Short Form (ALSSQOL-SF) Questionnaire will be completed at multiple times during the trial and the scores will be averaged.
- Mean change in average difference between active treatment and placebo for the Clinician's Global Impression (CGI) [ Time Frame: 36 weeks ]The CGI scales (assessing both severity [CGI-S] and improvement [CGI-I]) provides a brief assessment of the clinician's view of the patient's global functioning and severity of current disease state and can be utilized to assess for changes in disease progression over the course of a clinical trial.
- Mean change in average difference between active treatment and placebo for the Patient's Global Impression (PGI) [ Time Frame: 36 weeks ]The PGI scales (assessing both severity [PGI-S] and improvement [PGI-I]) provides a brief assessment of the patient's view global functioning and severity of current disease state and can be utilized to assess for changes in disease progression over the course of a clinical trial.
- Difference in the proportion of patients utilizing health economic outcome measures [ Time Frame: 36 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04098406
|Contact: Robert Glanzman, MDfirstname.lastname@example.org|
|Contact: Austin Ryndersemail@example.com|
|Australia, New South Wales|
|University of Sydney Brain and Mind Centre||Recruiting|
|Sydney, New South Wales, Australia, 2050|
|Contact: William Hunyh +61 (2) 9114 4250 firstname.lastname@example.org|
|Contact: Eleanor Ramsey, Research coordinator +61 2 9351 0976 email@example.com|
|Sydney, New South Wales, Australia, 2145|
|Contact: Pavarthi Menon, PhD, MD, MBBS, FRACP, MRCP +61 (2) 8890 8738 firstname.lastname@example.org|
|Contact: Julie Ryder, Clinical Research Nurse +61 (2) 8890 8738 Julie.Ryder@health.nsw.gov.au|
|Principal Investigator:||Parvarthi Menon, PhD, MD, MBBS||Westmead Hospital|
|Principal Investigator:||William Huynh, MD||University of Sydney, Brain and Mind Centre|