A Safety and Biomarker Study of ALZT-OP1a in Subjects With Mild-Moderate ALS Disease

NCT04428775 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: AZT-006
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 6

Brief Summary

This is a Phase IIa, randomized, open-label, multi-center, multi-dose study for subjects with mild to moderate ALS. The protocol is designed to determine whether ALZT-OP1a treatment will positively impact neuro-inflammatory biomarkers and slow down or arrest functional decline in subjects with mild to moderate ALS.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS; Amyotrophic Lateral Sclerosis; Lou Gehrig's disease; mild ALS; moderate ALS; mild to moderate ALS

Outcome Measures

Primary Outcomes (1)

• Plasma Biomarkers

  To measure the effect of ALZT-OP1a treatment on selected plasma biomarkers in ALS patients. Candidate biomarkers in ng/mL include: Beta-tryptase, Beta-Hexosaminidase Candidate biomarkers in pg/mL include: CXCL1, interferon-y, interleukin (IL)-1a, IL-1b, IL-2, IL-5, IL-6, IL-8, IL-10, IL-15, IL-17, macrophage inflammatory protein (MIP)-1a, MIP-1b, monocyte chemoattractant protein (MCP)-1, neurofilament light protein (NfL), tumor necrosis factor (TNF)-a, and vascular endothelial growth factor (VEGF)

  up to 12 weeks

Secondary Outcomes (11)

• Changes from baseline in ALS disease progression

  up to 12 weeks

• Time to Event Requiring Respiratory Support

  up to 12 weeks

• Changes from baseline in pulmonary function (forced vital capacity)

  up to 12 weeks

• Changes from baseline in pulmonary function (peak inspiratory flow rate)

  up to 12 weeks

• Incidence of adverse event (tolerability) related to ALZT-OP1a

  up to 12 weeks

Study Arms (2)

Group I (Low Dose)

EXPERIMENTAL

Group I (n=40) will receive treatment regimen of ALZT-OP1a (cromolyn) 17.1 mg/twice a day (bid) (total of 34.2 mg/day)

Drug: ALZT-OP1a (cromolyn)

Group II (High Dose)

EXPERIMENTAL

Group II (n=40) will receive treatment regimen of ALZT-OP1a (cromolyn) 34.2 mg/bid (total of 68.4 mg/day)

Drug: ALZT-OP1a (cromolyn)

Interventions

ALZT-OP1a (cromolyn) DRUG

1. Mast cell stabilizer 2. Neuroinflammatory microglial modulator 3. anti-inflammatory

Also known as: Cromolyn, Cromolyn sodium, Sodium cromoglycate

Group I (Low Dose); Group II (High Dose)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects aged 18-75 years, both inclusive;
• Must provide written informed consent before any study related procedures;
• Should be capable to complete all trial related procedures, assessments and visits in the judgement of Investigator;
• Familial or sporadic ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria;
• Disease duration from ALS diagnosis ≤24 months;
• ALSFRS-R total score ≥ 36 at screening visit;
• ALSFRS-R Breathing sub-score should be ≥9 at the time of screening;
• ALSFRS-R Bulbar sub-score should be ≥9 at the time of screening;
• Peak inspiratory flow rate (PIFR) ≥ 100 L/minute;
• Forced vital capacity (FVC) \>70% of predicted value;
• Participant must be receiving treatment with stable dose of standard of care treatment for ≥30 days prior to signing informed consent.

You may not qualify if:

• Subjects with bulbar-onset ALS;
• Any use of non-invasive ventilation (e.g., continuous positive airway pressure, non-invasive bi-level positive airway pressure or non-invasive volume ventilation) for any portion of the day, or mechanical ventilation via tracheostomy, or on any form of oxygen supplementation;
• Any other significant neurological disorder which can interfere with study assessments, e.g., significant cognitive impairment and/or clinical dementia;
• Significant psychiatric illness like schizophrenia, bipolar disorder etc. Subjects with depression can be included, only if the depression has been stable and no episode of major depression has occurred in past one year;
• Severe cardiac disease (e.g.,corrected QT interval \> 500ms), Torsade de Pointes, evidence of significant heart failure (New York Heart Association \[NYHA\] Class 3 or greater, myocardial infarction or unstable angina in the 6 months prior to screening);
• Any moderate-to-severe pulmonary disease or difficulty taking inhaled drugs;
• Inability to tolerate the administration of an oral inhaled powder via dry powder inhaler (DPI);
• Has taken any investigational study drug within 30 days or five half-lives of the drug, whichever is longer, prior to dosing;
• Currently taking cromolyn, or has taken cromolyn, within the past 12 months;
• Allergy to cromolyn or cromolyn products, such as Intal®, Nasalcrom®, Opticrom®, Gastrocrom®, etc.;
• Taking inhaled protein products on a chronic basis (such as insulin, parathyroid hormone \[PTH\], etc.);
• Subjects who weigh 88 lb (40 kg) or less, or, body mass index (BMI) of \<17.5 or \>35.0 at screening;
• Moderate-to-severe liver disease: aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin concentrations \>3 times the upper limit of normal; patients with hepatic diseases such as hepatic cirrhosis, hepatic cancer and active hepatitis
• Moderate-to-severe renal disease: creatinine clearance \<45 mL/min/1.73 m2 (by Cockcroft-Gault calculation);
• Any clinically significant disorder or laboratory abnormality that, in the investigator's opinion, could interfere with the subject's participation in the study, place the subject at increased risk, or confound interpretation of the study results;

Sponsors & Collaborators

• AZTherapies, Inc.: lead

Study Sites (6)

UCSD Altman Clinical and Translational Research Institute

La Jolla, California, 92037, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Wake Forest School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Related Publications (1)

• Granucci EJ, Griciuc A, Mueller KA, Mills AN, Le H, Dios AM, McGinty D, Pereira J, Elmaleh D, Berry JD, Paganoni S, Cudkowicz ME, Tanzi RE, Sadri-Vakili G. Cromolyn sodium delays disease onset and is neuroprotective in the SOD1G93A Mouse Model of amyotrophic lateral sclerosis. Sci Rep. 2019 Nov 27;9(1):17728. doi: 10.1038/s41598-019-53982-w.

  PMID: 31776380 BACKGROUND

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Cromolyn Sodium

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)

Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• David R. Elmaleh, PhD

  AZTherapies, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two doses of ALZT-OP1a (cromolyn) are being evaluated in this study. Each dose of ALZT-OP1a (cromolyn) will be co-administered with a stable dose of ALS standard-of-care treatment as prescribed by their physician.

Study Record Dates

• First Submitted: June 3, 2020
• First Posted: June 11, 2020
• Study Start: September 8, 2020
• Primary Completion: October 1, 2021
• Study Completion: October 1, 2021
• Last Updated: November 8, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)