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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04428775
Recruitment Status : Recruiting
First Posted : June 11, 2020
Last Update Posted : September 10, 2020
Sponsor:
Information provided by (Responsible Party):
AZTherapies, Inc.

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.

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: ALZT-OP1a (cromolyn) Phase 2

Detailed Description:

This Phase IIa study is designed as a randomized, open-label, multi-center, multi-dose study for subjects with mild to moderate ALS. The study will evaluate 1) safety, 2) tolerability, 3) changes in physical function measured using the ALSFRS-R, 4) two doses of ALZT-OP1a in order to determine an optimal and effective dose that could positively impact neuro-inflammatory biomarkers, and 5) to demonstrate preliminary evidence if this treatment could potentially slow down or arrest functional decline in subjects with mild to moderate ALS.

Up to 80 evaluable subjects will be randomly assigned to one of two treatment groups: Group I (n=40) will consist of low dose ALZT-OP1a, administered via dry powder inhalation; OR Group II (n=40), which will consist of high dose ALZT-OP1a, administered via dry powder inhaler.

Subjects will dose for 12 weeks and will be asked to return to the site for scheduled visits and biomarker collection at Week 4, Week 8, and Week 12.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Phase IIa, Randomized, Open-label, Multi-Center, Multi-Dose Study to Evaluate the Effects of ALZT-OP1a in Subjects With Mild-Moderate Stage Amyotrophic Lateral Sclerosis (ALS)
Actual Study Start Date : September 8, 2020
Estimated Primary Completion Date : July 15, 2021
Estimated Study Completion Date : October 15, 2021


Arm Intervention/treatment
Experimental: Group I (Low Dose)
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)
  1. Mast cell stabilizer
  2. Neuroinflammatory microglial modulator
  3. anti-inflammatory
Other Names:
  • Cromolyn
  • Cromolyn sodium
  • Sodium cromoglycate

Experimental: Group II (High Dose)
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)
  1. Mast cell stabilizer
  2. Neuroinflammatory microglial modulator
  3. anti-inflammatory
Other Names:
  • Cromolyn
  • Cromolyn sodium
  • Sodium cromoglycate




Primary Outcome Measures :
  1. Plasma Biomarkers [ Time Frame: up to 12 weeks ]

    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)



Secondary Outcome Measures :
  1. Changes from baseline in ALS disease progression [ Time Frame: up to 12 weeks ]
    Measured by ALS Functional Rating Scale-Revised (ALSFRS-R) - Questionnaire

  2. Time to Event Requiring Respiratory Support [ Time Frame: up to 12 weeks ]
    Measured by the time to event requiring full-time or nearly full-time respiratory support from baseline by treatment arm.

  3. Changes from baseline in pulmonary function (forced vital capacity) [ Time Frame: up to 12 weeks ]
    Measured by changes in forced vital capacity (FVC) in percent predicted value from baseline by treatment arm.

  4. Changes from baseline in pulmonary function (peak inspiratory flow rate) [ Time Frame: up to 12 weeks ]
    Measured by changes in peak inspiratory flow rate (PIFR) in liters per minute from baseline by treatment arm.

  5. Incidence of adverse event (tolerability) related to ALZT-OP1a [ Time Frame: up to 12 weeks ]
    Evaluated by number and percentage of unexpected adverse events by treatment arm.

  6. Number of participants with abnormal vital signs [ Time Frame: up to 12 weeks ]

    Measured by changes in systolic / diastolic blood pressure, pulse rate, respiratory rate, and body temperature from baseline by treatment arm.

    The data will also be presented in shift tables as within normal limits, clinically significant, not clinically significant.


  7. Number of participants with abnormal physical or neurological examinations [ Time Frame: up to 12 weeks ]

    Review of all body systems and changes evaluated for clinical significance from baseline by treatment arm.

    The data will also be presented in shift tables as within normal limits, clinically significant, not clinically significant.


  8. Number of participants with abnormal electrocardiograms (ECGs) [ Time Frame: up to 12 weeks ]

    Measured by changes in heart rate, PR interval, QRS complex, and QT interval from baseline by treatment arm.

    The data will also be presented in shift tables as within normal limits, clinically significant, not clinically significant.


  9. Number of participants with treatment emergent clinically significant laboratory assessments [ Time Frame: up to 12 weeks ]

    The abnormal values will be presented by treatment arm from baseline.

    The data will also be presented in shift tables as within normal limits, clinically significant, not clinically significant.


  10. Changes from baseline in suicidal ideation and behavior [ Time Frame: up to 12 weeks ]
    Measured by changes in Columbia Suicide Severity Rating Scale (C-SSRS) from baseline; minimum score: 0 maximum score: 10; lower values represent a better outcome.

  11. The number of study dropouts due to serious, unanticipated treatment emergent adverse events [ Time Frame: up to 12 weeks ]
    The dropouts will be presented by treatment arm from baseline.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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;
  • Pregnant or breast-feeding females or sexually active females with childbearing potential, if no adequate contraceptive measures are used.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04428775


Contacts
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Contact: David R. Elmaleh, PhD 617-318-3430 delmaleh@aztherapies.com
Contact: David Brazier 617-318-3428 david.brazier@aztherapies.com

Locations
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United States, North Carolina
Wake Forest School of Medicine Recruiting
Winston-Salem, North Carolina, United States, 27157
Sponsors and Collaborators
AZTherapies, Inc.
Investigators
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Study Director: David R. Elmaleh, PhD AZTherapies, Inc.
Publications:
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Responsible Party: AZTherapies, Inc.
ClinicalTrials.gov Identifier: NCT04428775    
Other Study ID Numbers: AZT-006
First Posted: June 11, 2020    Key Record Dates
Last Update Posted: September 10, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AZTherapies, Inc.:
ALS
Amyotrophic Lateral Sclerosis
Lou Gehrig's disease
mild ALS
moderate ALS
mild to moderate ALS
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Cromolyn Sodium
Anti-Asthmatic Agents
Respiratory System Agents