Evaluate PU-AD in Subjects With Amyotrophic Lateral Sclerosis

NCT04505358 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: PU-AD-SD-0202
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a multicenter, Phase 2a, randomized, double-blind, placebo-controlled pilot study to assess the biological activity, safety and pharmacokinetics of PU-AD compared to placebo in ALS. It will be conducted in approximately 20 sites in the US. Approximately 30 subjects will be enrolled in this study; subjects will be randomized 3:2 to receive either PU-AD 30 mg or matching placebo qd, added onto any current stable background treatment.

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Outcome Measures

Primary Outcomes (10)

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

  Clinical effect outcome assessments change from baseline (CFB)

  12 weeks

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

  Clinical effect outcome assessments change from baseline (CFB)

  24 weeks

• Slow Vital Capacity (SVC)

  Clinical effect outcome assessments change from baseline (CFB)

  12 weeks

• Slow Vital Capacity (SVC)

  Clinical effect outcome assessments change from baseline (CFB)

  24 weeks

• Handgrip strength using hand-held dynamometry

  Clinical effect outcome assessments change from baseline (CFB)

  12 weeks

• Handgrip strength using hand-held dynamometry

  Clinical effect outcome assessments change from baseline (CFB)

  24 weeks

• 6 Minute Walk Test (6MWT)

  Clinical effect outcome assessments change from baseline (CFB)

  12 weeks

• 6 Minute Walk Test (6MWT)

  Clinical effect outcome assessments change from baseline (CFB)

  24 weeks

• Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS)

  Clinical effect outcome assessments change from baseline (CFB)

  12 weeks

• Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS)

  Clinical effect outcome assessments change from baseline (CFB)

  24 weeks

Secondary Outcomes (10)

• Blood biomarkers (neurofilament light chain [NfL], phosphorylated neurofilament heavy chain [pNfH], Super oxide dismutase 1 (SOD1)

  12 weeks

• Blood biomarkers (neurofilament light chain [NfL], phosphorylated neurofilament heavy chain [pNfH], Super oxide dismutase 1 (SOD1)

  24 weeks

• CSF biomarkers (total tau [t-tau], phosphorylated tau231 [p-tau231], Neurofilament light chain (NfL), phosphorylated neurofilament heavy chain (pNfH), glial fibrillary acidic protein [GFAP], Transactive DNA binding protein 43 (TDP 43)

  12 weeks

• CSF biomarkers (total tau [t-tau], phosphorylated tau231 [p-tau231], NfL, pNfH, glial fibrillary acidic protein [GFAP], TDP 43

  24 weeks

• Urinary biomarker (P75 extracellular domain [p75ECD])

  12 weeks

Study Arms (2)

30 mg PU AD 3:2 ratio

EXPERIMENTAL

will be administered orally, as 30 mg active dose strength tablets qd on an empty stomach (1 hour prior to food or 2 hours after), at about the same time each day, via standard of care procedures at the site or at home. All subjects will have their first dose administered in clinic following completion of all baseline assessments

Drug: PU-AD

30 mg Placebo 3:2 ratio

PLACEBO COMPARATOR

will be administered orally, as 30 mg placebo tablets (placebo has no active ingredients) qd on an empty stomach (1 hour prior to food or 2 hours after), at about the same time each day, via standard of care procedures at the site or at home. All subjects will have their first dose administered in clinic following completion of all baseline assessments

Drug: Placebo

Interventions

PU-AD DRUG

active vs placebo

Also known as: active

30 mg PU AD 3:2 ratio

Placebo DRUG

active vs placebo

Also known as: non active

30 mg Placebo 3:2 ratio

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of ALS classified as Clinically Probable ALS or Clinically Definite ALS according to the El Escorial Revised Criteria4
• ALS onset ≤ 18 months from Screening
• Male or female aged 20 to 80 years old (inclusive)
• ALSFRS-R ≥ 30
• SVC ≥ 60% of predicted at Screening
• Willing and able to provide informed consent
• Concurrent medications riluzole and edaravone are permitted as long as the regimen is stable for at least 4 weeks prior to randomization and is expected to remain unchanged during the course of the study
• Able to swallow tablets
• Has been stable on medications that affect the CNS, for at least 4 weeks (including antidepressants, hypnotics and antipsychotics) and dose is not expected to change during the trial
• Willing to abstain from benzodiazepine or other CNS depressant treatment for 24 hours prior to each clinic visit and night-time hypnotics for 8 hours prior to each clinic visit
• Negative serum pregnancy test at Screening, for female subjects of childbearing potential
• Male subjects:
• Male subjects with female partners of childbearing potential are eligible to participate if they agree to ONE of the following methods of contraception from 21 days before the first dose of IMP through 4 months after the last dose of the IMP:
• Abstinence from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
• Use of a male condom plus partner use of a contraceptive method with a failure rate of \< 1% per year when having penile-vaginal intercourse with a woman of childbearing potential who is not currently pregnant.

You may not qualify if:

• Dependence on invasive or non-invasive mechanical ventilation (excluding continuous positive airway pressure for sleep apnea)
• Has current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterological, respiratory, endocrinologic, neurologic (other than ALS), psychiatric, infectious, immunologic or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses of safety and pharmacologic effect in this study
• Has a life expectancy of \<1 years
• Has had a history within the last 5 years of a serious infectious disease affecting the brain or head trauma resulting in protracted loss of consciousness
• Has a history within the last 5 years of a primary or recurrent malignant disease with the exception of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ or in situ prostate cancer with a normal prostate specific antigen post treatment
• Has a known history of human immunodeficiency virus, clinically significant multiple or severe drug allergies or severe post treatment hypersensitivity reactions
• Has a "yes" answer to Columbia Suicide Severity Rating Scale (C-SSRS) suicidal ideation item 4 or 5, or any suicidal behavior assessment within 6 months of Screening, or has been hospitalized or treated for suicidal behavior in the past 5 years before Screening
• Has a history of chronic alcohol or drug abuse/dependence within the past 5 years
• Transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year prior to Screening
• History of bleeding disorder or predisposing conditions, blood clotting or clinically significant abnormal results on coagulation profile at Screening, as determined by the investigator
• History of unstable angina, myocardial infarction, chronic heart failure (New York Heart Association Class III or IV) or clinically significant conduction abnormalities (e.g., unstable atrial fibrillation) within 1 year prior to Screening
• Clinically significant 12 lead electrocardiogram (ECG) abnormalities, as determined by the investigator
• Indication of impaired liver function as shown by an abnormal liver function profile at Screening (e.g., repeated values of aspartate aminotransferase \[AST\] and alanine aminotransferase \[ALT\] ≥ 2 × the upper limit of normal \[ULN\] and/or indication of impaired renal function at Screening) (e.g., repeated values of creatinine and blood urea nitrogen \[BUN\] ≥ 1.5 × ULN or estimated glomerular filtration rate \[GFR\] \< 45 mL/minute/1.73 m2 and corroborating medical history and physical examination)
• Any major surgery or trauma within 12 weeks of Screening or during the Screening Period or any surgery planned during the study
• Has active ocular condition, that in the opinion of the investigator, may alter visual acuity during the course of the study

Sponsors & Collaborators

• Samus Therapeutics, Inc.: lead

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Exercise

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Michael Silverman, MD

  Samus Therapeutics Consultant

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Packages will be labeled to mask the distinction between PU AD and placebo.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3:2 randomization

Study Record Dates

• First Submitted: July 23, 2020
• First Posted: August 10, 2020
• Study Start: January 1, 2023
• Primary Completion: December 1, 2024
• Study Completion: January 1, 2025
• Last Updated: November 17, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share