HEALEY ALS Platform Trial - Regimen C CNM-Au8

• ClinicalTrials.gov Identifier: NCT04414345
• Recruitment Status: Completed
• First Posted: June 4, 2020
• Results First Posted: July 25, 2023
• Last Update Posted: July 25, 2023
• Sponsor: Merit E. Cudkowicz, MD
• Collaborator: Clene Nanomedicine
• Information provided by (Responsible Party): Merit E. Cudkowicz, MD, Massachusetts General Hospital

Study Description

Brief Summary:

The HEALEY ALS Platform Trial is a perpetual multi-center, multi-regimen clinical trial evaluating the safety and efficacy of investigational products for the treatment of ALS.

Regimen C will evaluate the safety and efficacy of a single study drug, CNM-Au8, in participants with ALS.

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis	Drug: CNM-Au8; Drug: Matching Placebo	Phase 2; Phase 3

Detailed Description:

The HEALEY ALS Platform Trial is a perpetual multi-center, multi-regimen clinical trial evaluating the safety and efficacy of investigational products for the treatment of ALS. This trial is designed as a perpetual platform trial. This means that there is a single Master Protocol dictating the conduct of the trial. The HEALEY ALS Platform Trial Master Protocol is registered as NCT04297683.

Once a participant enrolls into the Master Protocol and meets all eligibility criteria, the participant will be eligible to be randomized into any currently enrolling regimen. All participants will have an equal chance of being randomized to any currently enrolling regimen.

If a participant is randomized to Regimen C - CNM-Au8, the participant will complete a screening visit to assess additional Regimen C eligibility criteria. Once Regimen C eligibility criteria are confirmed, participants will complete a baseline assessment and be randomized in a 3:1 ratio to either active CNM-Au8 or matching placebo.

Regimen C will enroll by invitation, as participants may not choose to enroll in Regimen C. Participants must first enroll into the Master Protocol and be eligible to participate in the Master Protocol before being able to be randomly assigned to Regimen C.

For a list of enrolling sites, please see the HEALEY ALS Platform Trial Master Protocol under NCT04297683.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 161 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: HEALEY ALS Platform Trial - Regimen C CNM-Au8
• Actual Study Start Date: July 30, 2020
• Actual Primary Completion Date: April 13, 2022
• Actual Study Completion Date: March 7, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: CNM-Au8; Drug: CNM-Au8 Administration: Oral Dosage: 30 mg or 60 mg daily	Drug: CNM-Au8; Drug: CNM-Au8 Administration: Oral Dosage: 30 mg or 60 mg daily
Placebo Comparator: Matching Placebo; Administration: Oral Dosage: 2 bottles daily	Drug: Matching Placebo; Drug: Matching Placebo Administration: Oral Dosage: 2 bottles daily

Outcome Measures

Primary Outcome Measures :

1. Disease Progression as Assessed by the ALSFRS-R Total Score [ Time Frame: Baseline to 24 Weeks ]
   Change in disease severity as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) total score using a Bayesian repeated measures model that accounts for loss to follow-up due to mortality. Each type of function is scored from 4 (normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0. Patients with higher scores have more physical function.
2. Mortality Event Rate [ Time Frame: Baseline to 24 Weeks ]
   Mortality is defined as death or death equivalent. A participant is determined to meet the criteria of death equivalent if permanent assisted ventilation (PAV) is used for more than 22 hours per day for more than seven days in a row. The rate of mortality was estimated from a Bayesian shared-parametric model that assumed exponentially distributed survival times.

Secondary Outcome Measures :

1. Respiratory Function [ Time Frame: Baseline to 24 Weeks ]
   Change in respiratory function as assessed by slow vital capacity (SVC).
2. Muscle Strength [ Time Frame: Baseline to 24 Weeks ]
   Change in muscle strength as measured isometrically using hand-held dynamometry (HHD).
3. Number of Participants That Experienced Death or Death Equivalent [ Time Frame: 24 Weeks ]
   The number of participants who died or met the criterion for a death equivalent from the date of their baseline visit to the end of the Week 24visit window (generally 175 days after baseline). The death equivalent criterion is use of permanent assisted ventilation (PAV) for more than 22hours per day for more than 7 days in a row.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• No additional inclusion criteria beyond the inclusion criteria specified in the Master Protocol (NCT NCT04297683).

Exclusion Criteria:

• The following exclusion criterion is in addition to the exclusion criteria specified in the Master Protocol (NCT NCT04297683).

  1. History of allergy to gold, gold salts, or colloidal gold preparations.

Contacts and Locations

Locations

United States, Massachusetts

Healey Center for ALS at Mass General

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Merit E. Cudkowicz, MD

Clene Nanomedicine

Investigators

• Principal Investigator: Merit Cudkowicz; Massachusetts General Hospital

  Study Documents (Full-Text)

Documents provided by Merit E. Cudkowicz, MD, Massachusetts General Hospital:

Study Protocol  [PDF] November 22, 2021

Statistical Analysis Plan  [PDF] July 22, 2022

More Information

• Responsible Party: Merit E. Cudkowicz, MD, Chief, Neurology Department, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT04414345
• Other Study ID Numbers: 2019P003518C
• First Posted: June 4, 2020
• Results First Posted: July 25, 2023
• Last Update Posted: July 25, 2023
• Last Verified: June 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merit E. Cudkowicz, MD, Massachusetts General Hospital:

ALS; Placebo-Controlled; Double-Blind; Regimen-Specific Appendix; Lou Gehrig's Disease; CNM-Au8; Clene Nanomedicine

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases