Amyotrophic Lateral SclerosisPhase 2NCT04428775
A Safety and Biomarker Study of ALZT-OP1a in Subjects With Mild-Moderate ALS Disease
A Phase 2 study testing ALZT-OP1a (cromolyn) in people with Amyotrophic Lateral Sclerosis, run by AZTherapies, Inc. at 6 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- ALZT-OP1a (cromolyn)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 6 sitesUnited States
- Study dates
- 8 Sep 2020to 1 Oct 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Show all 11Show fewer
- 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.
Who cannot join
- 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;
Show all 16Show fewer
- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Mayo Clinic
Jacksonville, Florida, 32224
UCSD Altman Clinical and Translational Research Institute
La Jolla, California, 92037
Hospital for Special Surgery
New York, New York, 10021
Columbia University Medical Center
New York, New York, 10032
Oregon Health & Science University
Portland, Oregon, 97239
Wake Forest School of Medicine
Winston-Salem, North Carolina, 27157
About this study
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)
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.
Read the 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.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- ALZT-OP1a (cromolyn)
- Keywords
- ALS, Amyotrophic Lateral Sclerosis, Lou Gehrig's disease, mild ALS, moderate ALS, mild to moderate ALS
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALZT-OP1a (cromolyn)Drug
Also called Cromolyn, Cromolyn sodium, Sodium cromoglycate
- Mast cell stabilizer
- Neuroinflammatory microglial modulator
- anti-inflammatory
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Drug: ALZT-OP1a (cromolyn) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: up to 12 weeks
Secondary outcomes (11)
Changes from baseline in ALS disease progression
Measured by ALS Functional Rating Scale-Revised (ALSFRS-R) - Questionnaire
Measured: up to 12 weeks
Time to Event Requiring Respiratory Support
Measured by the time to event requiring full-time or nearly full-time respiratory support from baseline by treatment arm.
Measured: up to 12 weeks
Changes from baseline in pulmonary function (forced vital capacity)
Measured by changes in forced vital capacity (FVC) in percent predicted value from baseline by treatment arm.
Measured: up to 12 weeks
Changes from baseline in pulmonary function (peak inspiratory flow rate)
Measured by changes in peak inspiratory flow rate (PIFR) in liters per minute from baseline by treatment arm.
Measured: up to 12 weeks
Incidence of adverse event (tolerability) related to ALZT-OP1a
Evaluated by number and percentage of unexpected adverse events by treatment arm.
Measured: up to 12 weeks
Number of participants with abnormal vital signs
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.
Measured: up to 12 weeks
Number of participants with abnormal physical or neurological examinations
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.
Measured: up to 12 weeks
Number of participants with abnormal electrocardiograms (ECGs)
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.
Measured: up to 12 weeks
Number of participants with treatment emergent clinically significant laboratory assessments
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.
Measured: up to 12 weeks
Changes from baseline in suicidal ideation and behavior
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.
Measured: up to 12 weeks
The number of study dropouts due to serious, unanticipated treatment emergent adverse events
The dropouts will be presented by treatment arm from baseline.
Measured: up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start8 Sep 2020
- Primary completion1 Oct 2021
- Study completion1 Oct 2021
Why it stopped: Low enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- AZTherapies, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David R. Elmaleh, PhD, Study director, AZTherapies, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04428775
- Sponsor's protocol ID
- AZT-006
- Status last verified
- Jun 2021
- First submitted
- 3 Jun 2020
- Last updated
- 8 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31776380
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04428775
- Acronym / sponsor ID
- AZT-006
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- ALS, Amyotrophic Lateral Sclerosis, Lou Gehrig's disease, mild ALS, moderate ALS, mild to moderate ALS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low enrollment
- Enrolment
- 12 participants (actual)
- Lead sponsor
- AZTherapies, Inc.Industry (pharma, biotech, devices)
- Study start
- 8 Sep 2020 (actual)
- Primary completion
- 1 Oct 2021 (actual)
- Study completion
- 1 Oct 2021 (actual)
- First posted
- 11 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Group I (Low Dose) | Experimental | Drug: ALZT-OP1a (cromolyn)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) |
| Group II (High Dose) | Experimental | Drug: ALZT-OP1a (cromolyn)Group II (n=40) will receive treatment regimen of ALZT-OP1a (cromolyn) 34.2 mg/bid (total of 68.4 mg/day) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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;
Key exclusion criteria (16 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ALZT-OP1a (cromolyn)Also: Cromolyn, Cromolyn sodium, Sodium cromoglycate1. Mast cell stabilizer 2. Neuroinflammatory microglial modulator 3. anti-inflammatory | Drug | Group I (Low Dose), Group II (High Dose) |
Primary outcome
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)
11 secondary outcomes
Changes from baseline in ALS disease progression
Time frame: up to 12 weeks
Time to Event Requiring Respiratory Support
Time frame: up to 12 weeks
Changes from baseline in pulmonary function (forced vital capacity)
Time frame: up to 12 weeks
Changes from baseline in pulmonary function (peak inspiratory flow rate)
Time frame: up to 12 weeks
Incidence of adverse event (tolerability) related to ALZT-OP1a
Time frame: up to 12 weeks
Number of participants with abnormal vital signs
Time frame: up to 12 weeks
Number of participants with abnormal physical or neurological examinations
Time frame: up to 12 weeks
Number of participants with abnormal electrocardiograms (ECGs)
Time frame: up to 12 weeks
Number of participants with treatment emergent clinically significant laboratory assessments
Time frame: up to 12 weeks
Changes from baseline in suicidal ideation and behavior
Time frame: up to 12 weeks
The number of study dropouts due to serious, unanticipated treatment emergent adverse events
Time frame: up to 12 weeks
Results and safety
The study was stopped early (reason given: Low enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2021.
- Background: PubMed 31776380Granucci 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.
- Individual participant dataSharing planned: No
Related trials for Amyotrophic Lateral Sclerosis
RecruitingPhase 1/2
Study is to Assess the Safety and Tolerability of VTx-002 in Participants With ALS
Amyotrophic Lateral Sclerosis
Not yet recruiting
A Study on the Addition of Alsum30 for the Treatment of Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis (ALS), Bacillus Coagulans
Active, not recruiting
Functional Outcomes and Control Using Synchron BCI - Australia
Neurologic Disorder, Neurologic Diseases
Not yet recruitingPhase 1
Safety, Tolerability, and Pharmacodynamic Exploration of Orelabrutinib in Patients With Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic Lateral Sclerosis (ALS)
Recruiting
Clinical Outcome Assessment for AT & BCI
Spinal Cord Injury, ALS (Amyotrophic Lateral Sclerosis)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David R. Elmaleh, PhD study director
AZTherapies, Inc.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ALZT-OP1a (cromolyn) in people with Amyotrophic Lateral Sclerosis, run by AZTherapies, Inc. at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma Biomarkers (time frame: up to 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04428775, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2021.