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.
This was 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 were screened over up to a 6-week period. Patients who met the inclusion criteria and none of the exclusionary criteria were enrolled into the clinical study. Patients were randomized 1:1 into one of two groups: either active treatment with CNM-Au8 30 mg or Placebo. All patients received their randomized oral treatment daily over thirty-six (36) consecutive weeks during the Treatment Period. There were up to four study periods: 1. Up to a six (6) week screening period (Screening Period); 2. A thirty-six (36) week blinded randomized treatment period (Treatment Period); 3. Up to a forty-eight (48) week optional open-label extension period (Open-Label Period); 4. 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 received 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 completed a safety follow-up visit 4-weeks following study drug discontinuation. An independent DSMB was 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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
45
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.
Placebo was liquid with identical color and taste
University of Sydney Brain and Mind Centre
Sydney, New South Wales, Australia
Westmead Hospital
Sydney, New South Wales, Australia
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%.
Time frame: 36 weeks
Percentage Mean Change in the Average Difference Between Active Treatment and Placebo From Baseline for Respiratory Function as Measured by Forced Vital Capacity (FVC).
Mean change in FVC - Forced Vital Capacity.
Time frame: 36 weeks
Mean Absolute Change of the Average Difference Between Active Treatment and Placebo From Baseline Through Week 36 for the MUNIXscore(4).
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. MUNIX will be reviewed via electromyography for the Abductor Pollicus Brevis (APB), Abductor Digiti Minimi (ADM), Biceps Brachii (BB), and Tibialis Anterior (TA). MUNIXscore(4) is the sum of the respective MUNIX values for the above mentioned muscle groups. A higher MUNIX value signifies greater muscle function. A greater decrease in the Mean absolute change signifies worsening muscle function.
Time frame: 36 weeks
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