The purpose of this study is to test the effects of PHENOGENE-1A, which is the treatment under investigation in this study. This research will investigate if PHENOGENE-1A can help people with ALS by measuring their function using the ALS Functional Rating Scale Revised (ALSFRS-R), measuring lung function using pulmonary function tests (PFTs), such as forced vital capacity (FVC), and measuring neuro-inflammatory biomarkers in the blood.
This is a Phase IIB, randomized, double-blind, placebo-controlled study designed to assess the effects of PHENOGENE-1A (oral inhalation via dry powder inhaler \[DPI\]) in subjects with mild to moderate ALS disease. Eligible subjects will be randomized to receive either low dose PHENOGENE-1A (34.2 mg per day: in 2 doses of 17.1 mg and matching placebo BID), high dose PHENOGENE-1A (68.4 mg per day: 34.2 mg BID), or placebo (2 matching placebo capsules BID) (see table below), in a 2:2:1 ratio. Subjects will receive treatment for a duration of 24 weeks. All subjects must be on a stable dose of Riluzole 50 mg BID (100 mg daily) for at least 4 weeks prior to randomization and must continue their Riluzole regimen, 50 mg BID (100 mg daily), as standard-of-care treatment, throughout the 24 week treatment period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
105
17.1 mg, BID, oral inhalation
34.2 mg, BID, oral inhalation via dry powder inhaler
Placebo comparator matched to active treatment.
Honor Health Neurology - Bob Bove Neuroscience Institute
Scottsdale, Arizona, United States
RECRUITINGUniversity of California San Diego
La Jolla, California, United States
Absolute change in ALSFRS-R total score from baseline to Week 24
To evaluate the effects of PHENOGENE-1A (cromolyn) on functional changes in subjects with mild to moderate ALS using the ALS Functional Rating Scale-Revised (ALSFRS-R).
Time frame: Baseline to Week 24
Incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
To evaluate the safety of PHENOGENE-1A following 24 weeks of twice daily (BID) treatment.
Time frame: Baseline to Week 24
Mean rank for CAFS at Week 24
To evaluate the effects of PHENOGENE-1A on function and survival using the Combined Assessment of Function and Survival (CAFS).
Time frame: Baseline to Week 24
Time to event requiring full-time or nearly full-time respiratory support
Time from randomization to the first of 7 consecutive days on which permanent assisted ventilation (invasive or non-invasive) was used for \>22 hours/day due to ALS progression.
Time frame: Randomization to Week 24
Mean change in percent predicted forced vital capacity (%FVC) from baseline to Week 24
To evaluate the effect of PHENOGENE-1A on respiratory changes.
Time frame: Baseline to Week 24
Mean change in peak inspiratory flow rate (PIFR) from baseline to Week 24
To evaluate changes in PIFR (L/min) during treatment.
Time frame: Baseline to Week 24
Absolute Values and Changes From Baseline in Vital Signs From Baseline to Week 24 by Treatment Arm
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50 mg, oral tablet, BID, standard of care treatment
Sutter Health - California Pacific Medical Center Research Institute
San Francisco, California, United States
RECRUITINGMayo Clinic Jacksonville
Jacksonville, Florida, United States
RECRUITINGLange Neurology
New York, New York, United States
RECRUITINGThomayer University Hospital - Fakultní Thomayerova nemocnice
Prague, Czechia
RECRUITINGCharité Centrum für Neurologie, Neurochirurgie und Psychiatrie
Berlin, Germany
RECRUITINGMichalski i Partnerzy Lekarze Spółka Partnerska
Krakow, Poland
RECRUITINGSP ZOZ Szpital Uniwersytecki w Krakowie
Krakow, Poland
RECRUITINGCentrum Medyczne NeuroProtect (NeuroProtect Medical Center)
Warsaw, Poland
RECRUITING...and 2 more locations
Vital signs will include: * Systolic blood pressure (mmHg) * Diastolic blood pressure (mmHg) * Pulse rate (beats per minute) * Respiratory rate (breaths per minute) * Body temperature (°C or °F, as recorded) Results will be summarized as: * Absolute values for each parameter at each scheduled visit. * Changes from baseline at each visit. * Summaries will be presented separately by treatment arm.
Time frame: Baseline to Week 24
Number and Percentage of Subjects With Abnormal Clinical Laboratory Values and Changes From Baseline to Week 24 by Treatment Arm
Safety laboratory assessments will include hematology, clinical chemistry, coagulation, and urinalysis panels. Each laboratory result will be classified as normal, abnormal (not clinically significant), or abnormal (clinically significant). Results will be summarized as: Number and percentage of subjects with abnormal laboratory values at each post-baseline visit, by treatment arm. Summary statistics for absolute values and changes from baseline at each visit.
Time frame: Baseline to Week 24
Number and Percentage of Subjects With Abnormal Physical Examination Findings From Baseline to Week 24 by Treatment Arm
The physical examination will assess head/neck, eyes, ears, nose/throat, cardiovascular, respiratory, abdominal, musculoskeletal, extremities, and skin systems. Each system will be classified as normal, abnormal (not clinically significant), or abnormal (clinically significant). Results will be summarized as the number and percentage of subjects with abnormal findings at each post-baseline visit.
Time frame: Baseline to Week 24
Number and Percentage of Subjects With Abnormal Neurological Examination Findings From Baseline to Week 24 by Treatment Arm
The neurological examination will assess mental status, motor function, sensory function, reflexes, and coordination/cerebellar function. Each domain will be classified as normal, abnormal (not clinically significant), or abnormal (clinically significant). Results will be summarized as the number and percentage of subjects with abnormal findings at each post-baseline visit.
Time frame: Baseline to Week 24
Number and Percentage of Subjects With Abnormal Electrocardiogram (ECG) Findings From Baseline to Week 24 by Treatment Arm
Standard 12-lead ECGs will be performed at protocol-specified visits. Parameters assessed will include: * Heart rate: 60-100 beats per minute (bpm) * PR interval: 120-200 milliseconds (ms) * QRS duration: 70-110 ms * QT interval: \< 440 ms in men, \< 460 ms in women * Corrected QT interval (QTcF, Fridericia's formula): \< 450 ms in men, \< 470 ms in women Each ECG result will be classified by the investigator as normal, abnormal (not clinically significant), or abnormal (clinically significant), using these ranges as reference. Results will be summarized as the number and percentage of subjects with abnormal ECG findings at each post-baseline visit.
Time frame: Baseline to Week 24
Number and Percentage of Subjects With Suicidal Ideation, Suicidal Behavior, or Self-Injurious Behavior Without Suicidal Intent on the Columbia Suicide Severity Rating Scale (C-SSRS) From Baseline to Week 24 by Treatment Arm
The Columbia Suicide Severity Rating Scale (C-SSRS) will be administered at protocol-specified visits to assess suicidal ideation, suicidal behavior, and self-injurious behavior without suicidal intent. * Suicidal ideation will be captured using categories 1-5 of the C-SSRS (ranging from passive wish to be dead to active suicidal ideation with plan and intent). * Suicidal behavior will be captured using categories 6-10 of the C-SSRS (preparatory acts, aborted attempts, interrupted attempts, and actual attempts). * Self-injurious behavior without suicidal intent will be reported separately. Results will be summarized as: Number and percentage of subjects with suicidal ideation, suicidal behavior, and self-injurious behavior without suicidal intent, compared between active treatment and placebo arms.
Time frame: Baseline to Week 24
Number and Percentage of Subjects Who Discontinue Study Participation Due to Adverse Events From Baseline to Week 24
The incidence of study discontinuation attributed to treatment-emergent adverse events (TEAEs) will be assessed. Results will be summarized as the number and percentage of subjects who withdraw from the study due to an adverse event, presented separately by treatment arm.
Time frame: Baseline to Week 24