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NCT04098406: RESCUE-ALS

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

Completed Phase 2 Results posted Last updated 3 July 2024
What this trial tests

Phase 2 trial testing CNM-Au8 in Amyotrophic Lateral Sclerosis in 45 participants. Completed in 13 July 2021.

Timeline
19 December 2019
Primary endpoint
13 July 2021
13 July 2021

Quick facts

Lead sponsorClene Nanomedicine
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment45
Start date19 December 2019
Primary completion13 July 2021
Estimated completion13 July 2021
Sites2 locations across Australia

Drugs / interventions tested

Conditions studied

Sponsor

Clene Nanomedicine — full company profile →

Who can join

Adults 30 to 80, any sex, with Amyotrophic Lateral Sclerosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Electromyography Measures of Disease Progression. Primary · 36 weeks

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 calculat

GroupValue95% CI
Placebo-39.6± 7.1
30 mg CNM-Au8-31.8± 6.6
Percentage Mean Change in the Average Difference Between Active Treatment and Placebo From Baseline for Respiratory Function as Measured by Forced Vital Capacity (FVC). Secondary · 36 weeks

Mean change in FVC - Forced Vital Capacity.

GroupValue95% CI
Placebo-20.3± 5.8
30 mg CNM-Au8-16.7± 5.4
Mean Absolute Change of the Average Difference Between Active Treatment and Placebo From Baseline Through Week 36 for the MUNIXscore(4). Secondary · 36 weeks

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 worsenin

GroupValue95% CI
Placebo-141.3± 27
30 mg CNM-Au8-123.6± 25
Mean Change in Average ALSFRS-R Score Secondary · 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. Maximum score is 40, minimum is 0. A higher score signifies greater function.

GroupValue95% CI
Placebo-5.8± 0.9
30 mg CNM-Au8-4.8± 0.8
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. Secondary · 36 weeks

Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R)

GroupValue95% CI
Placebo18
30 mg CNM-Au812
Placebo4
30 mg CNM-Au811
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 Secondary · 36 weeks

the Combined Assessment of Function and Survival (CAFS). CAFS ranks patients' clinical outcomes based on survival time and change in the ALS Functional Rating Scale-Revised (ALSFRS-R) score. Each patient's outcome is compared to every other patient's outcome, assigned a score, and the summed scores are ranked. The mean rank score for each treatment group can then be calculated. A higher mean CAFS score indicates a better group outcome. There is no maximum or minimum due to ranking.

GroupValue95% CI
Placebo-4.6± 5.2
30 mg CNM-Au84.4± 5.1
Time to ALS Clinical Worsening Secondary · 36 weeks

ALS Clinical Worsening is 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. This outcome measures the number of participants that experienced ALS clinical worsening event within the 36 week time frame.

GroupValue95% CI
Placebo13
30 mg CNM-Au85
Mean Change in Average Difference Between Active Treatment and Placebo for the ALSSQOL-Short Form Questionnaire (ALSSQOL-SF) Secondary · 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. Maximum score is 10, minimum score is 0. A higher score signifies a higher quality of life.

GroupValue95% CI
Placebo-1.2± 0.3
30 mg CNM-Au8-0.3± 0.2

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from the time of the signing of the Informed Consent to 28 days after the last day of study drug administration, up to 46 weeks.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 5/22 (23%)
Deaths: 2/22
30 mg CNM-Au8
Serious: 5/23 (22%)
Deaths: 1/23

Serious adverse events (10 terms)

ReactionSystemPlacebo30 mg CNM-Au8
Pneumonia aspirationRespiratory, thoracic and mediastinal disorders
Acute Respiratory FailureRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Respiratory FailureRespiratory, thoracic and mediastinal disorders
HaemorrhoidsRespiratory, thoracic and mediastinal disorders
Large intestine polypGastrointestinal disorders
FallInjury, poisoning and procedural complications
Femoral Neck FractureInjury, poisoning and procedural complications
Amyotrophic lateral sclerosisNervous system disorders
Motor neurone diseaseNervous system disorders
Other adverse events (55 terms — click to expand)

ReactionSystemPlacebo30 mg CNM-Au8
FallInjury, poisoning and procedural complications
LacerationInjury, poisoning and procedural complications
Pneumonia aspirationRespiratory, thoracic and mediastinal disorders
ContusionInjury, poisoning and procedural complications
NauseaGastrointestinal disorders
Chest InjuryInjury, poisoning and procedural complications
Ankle FractureInjury, poisoning and procedural complications
Back InjuryInjury, poisoning and procedural complications
Clavicle FractureInjury, poisoning and procedural complications
Femoral Neck FractureInjury, poisoning and procedural complications
Foot fractureInjury, poisoning and procedural complications
Head InjuryInjury, poisoning and procedural complications
Limb injuryInjury, poisoning and procedural complications
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Abdominal distensionGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
Abnormal faecesGastrointestinal disorders
Dry mouthGastrointestinal disorders
Gingival discolourationGastrointestinal disorders
HaemorrhoidsGastrointestinal disorders
Large intestine polypGastrointestinal disorders
Mouth ulcerationGastrointestinal disorders
ConjunctivitisInfections and infestations
Fungal infectionInfections and infestations
Lower respiratory tract infectionInfections and infestations
Oral candidiasisInfections and infestations
Otitis mediaInfections and infestations
PneumoniaInfections and infestations
Post procedural infectionInfections and infestations
Sweat gland infectionInfections and infestations
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
HaemoptysisRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Amyotrophic lateral sclerosisNervous system disorders
HeadacheNervous system disorders

Most-reported serious reactions: Pneumonia aspiration, Acute Respiratory Failure, Pulmonary embolism, Respiratory Failure, Haemorrhoids, Large intestine polyp, Fall, Femoral Neck Fracture.

Data from ClinicalTrials.gov NCT04098406 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Nanotherapeutics.
    Lamptey RNL, Chaulagain B, Trivedi R, Gothwal A, et al · · 2022 · cited 476× · PMID 35163773 · DOI 10.3390/ijms23031851
  2. Drug delivery to the central nervous system.
    Nance E, Pun SH, Saigal R, Sellers DL. · · 2022 · cited 224× · PMID 38464996 · DOI 10.1038/s41578-021-00394-w
  3. A Historical Review of Brain Drug Delivery.
    Pardridge WM. · · 2022 · cited 133× · PMID 35745855 · DOI 10.3390/pharmaceutics14061283
  4. Clinical translation of gold nanoparticles.
    Zhang R, Kiessling F, Lammers T, Pallares RM. · · 2023 · cited 108× · PMID 36045273 · DOI 10.1007/s13346-022-01232-4
  5. Applications and safety of gold nanoparticles as therapeutic devices in clinical trials.
    Yao L, Bojic D, Liu M. · · 2023 · cited 63× · PMID 37842655 · DOI 10.1016/j.jpha.2023.06.001
  6. Nanoparticle-Based Drug Delivery Systems: An Inspiring Therapeutic Strategy for Neurodegenerative Diseases.
    Duan L, Li X, Ji R, Hao Z, et al · · 2023 · cited 43× · PMID 37177342 · DOI 10.3390/polym15092196
  7. Blood-Brain Barrier-Targeting Nanoparticles: Biomaterial Properties and Biomedical Applications in Translational Neuroscience.
    Asimakidou E, Tan JKS, Zeng J, Lo CH. · · 2024 · cited 40× · PMID 38794182 · DOI 10.3390/ph17050612
  8. 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.
    Vucic S, Menon P, Huynh W, Mahoney C, et al · · 2023 · cited 40× · PMID 37396808 · DOI 10.1016/j.eclinm.2023.102036

Verify or expand the search:

Other trials of CNM-Au8

Trials testing the same drug.

Other recruiting trials for Amyotrophic Lateral Sclerosis

Currently open trials in the same condition.

Other Clene Nanomedicine trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing