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. (RESCUE-ALS)

Study Purpose:

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).

Disease:

Amyotrophic Lateral Sclerosis (ALS),  Familial ALS,  Sporadic ALS

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:

Enrolling

Phase:

Phase II

Study Chair(s)/Principal Investigator(s):

Parvarthi Menon, PhD, MD, MBBS Westmead Hospital
William Huynh, MD University of Sydney, Brain and Mind Centre

Clinicaltrials.gov ID (11 digit #):

NCT04098406

Neals Affiliated?

No

Coordinating Center Contact Information


Robert Glanzman, MD / .(JavaScript must be enabled to view this email address) / 801-676-9695
Austin Rynders / .(JavaScript must be enabled to view this email address) / 801-676-9695

Full Study Summary:

This is a multi-centre randomised, 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 (de Carvalho et al. 2008).

Patients may be screened over up to a 4-week period. Patients who meet the inclusion criteria and none of the exclusionary criteria will be enrolled into the clinical study.

Patients will be randomised 1:1 into one of two groups: either active treatment with CNM-Au8 30 mg or Placebo.

All patients will receive their randomised oral treatment daily over thirty-six (36) consecutive weeks during the Treatment Period.

There will be three study periods:

  1. Up to a four (4) week screening period (Screening Period);
  2. A thirty-six (36) week blinded randomised treatment period (Treatment Period);
  3. A four (4) week safety follow-up period (End-of-Study Assessment).

Per protocol all patients will receive their blinded and randomised oral treatment daily over at least 36 consecutive weeks during the Treatment Period. Following the end of the Treatment Period patients may be transitioned into an open-label extension period in a separate study protocol (e.g., RESCUE-ALS OLE).

For those patients not transitioning into the separate open-label extension study, patients will complete an EOS safety assessment 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 Sponsor:

Clene Nanomedicine

Participant Duration:

Estimated Enrollment:

42

Estimated Study Start Date:

01/01/2020

Estimated Study Completion Date:

06/30/2021

Posting Last Modified Date:

01/29/2020

Date Study Added to alsconsortium.org:

01/29/2020
  • Eligibility Criteria

    Gender:

    Female, Male

    Minimum Age:

    40

    Maximum Age:

    80

    Min Vital Capacity (% predicted normal):

    60

    Time since Symptom Onset:

    <24 months

    Time since Diagnosis:

    <12 months

    Can participants use Riluzole?

    Yes


    Inclusion Criteria:

    Able to understand and give written informed consent.
    Male or female patients aged 40 years or greater (inclusive) and less than 80 years of age at the time of ALS diagnosis.
    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 disese duration less than or equal to 12-months from diagnosis.

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

    • Current disease duration ≤ 75% of predicted duration
    • Predicted 3-month risk of survival at the time of screening ≥ 90%
    • Predicted 24-month risk of survival at the time of screening ≤ 85%

    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 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.

    Exclusion 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 post-randomisation, 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 10^9 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.
    Positive screen for drugs of abuse.
    History of gold allergy.
    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.

  • Site Contact Information

    University of Sydney Brain and Mind Centre
    William Hunyh / .(JavaScript must be enabled to view this email address) / +61 (2) 9114 4250
    Sydney, New South Wales 2050
    Australia

    Westmead Hospital
    Pavarthi Menon, PhD, MD, MBBS, FRACP, MRCP / .(JavaScript must be enabled to view this email address) / +61 (2) 8890 8738
    Julie Ryder / .(JavaScript must be enabled to view this email address) / +61 (2) 8890 8738
    Sydney, New South Wales 2145
    Australia