PHENOGENE-1A (cromolyn) treatment for people with mild to moderate ALS

A Phase IIB Randomized, Double-Blind, Placebo-Controlled, Multi-Dose Study to Evaluate the Effects of PHENOGENE-1A (Cromolyn) as an Adjuvant Treatment in Subjects With Mild to Moderate Amyotrophic Lateral Sclerosis (ALS)

This study will test whether inhaled PHENOGENE-1A (cromolyn) helps people with mild to moderate ALS maintain function and lung capacity over 24 weeks while they continue riluzole.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 105 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: PhenoNet, Inc. (industry)
• Locations: 17 sites (Scottsdale, Arizona and 16 other locations)
• Trial ID: NCT07142291 on ClinicalTrials.gov

What this trial studies

This is a Phase 2b, randomized, double-blind, placebo-controlled trial testing inhaled PHENOGENE-1A (cromolyn) delivered by dry powder inhaler in people with mild to moderate ALS. Participants are randomized 2:2:1 to low dose, high dose, or matching placebo and receive treatment for 24 weeks while remaining on stable riluzole therapy. Outcomes include change in ALS Functional Rating Scale-Revised (ALSFRS-R), pulmonary function tests such as forced vital capacity (FVC), and blood neuro-inflammatory biomarkers. Eligible participants are adults 18–75 with ALS symptom onset of motor weakness within 24 months who can complete study procedures and use the inhaler.

Who should consider this trial

Good fit: Adults aged 18–75 with mild to moderate ALS (symptom onset ≤24 months), able to use an inhaler and willing to remain on stable riluzole, are ideal candidates.

Not a fit: People with advanced ALS, symptom duration over 24 months, inability to use an inhaler, or unstable/contraindicated riluzole use are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the drug could slow functional decline and help preserve breathing in people with early-stage ALS.

How similar studies have performed: Applying cromolyn to ALS is relatively novel with limited direct clinical evidence in ALS, though cromolyn is an established anti-inflammatory medication in other conditions and has some preclinical neuroinflammation data.

Eligibility criteria

Inclusion Criteria:

1. Diagnosis of ALS; the diagnosis of ALS defined by revised El Escorial criteria as follows:

   1. Evidence of lower motor neuron (LMN) degeneration by clinical, electrophysiological, or neuropathological examination.
   2. Evidence of upper motor neuron (UMN) degeneration by clinical examination.
   3. Progressive spread of symptoms or signs within a region or to other regions, as determined by clinical examination or the history of disease progression.
   4. Absence of electrophysiological, neuroimaging, or pathological evidence of other diseases that might explain the UMN or LMN degeneration and exclusion of other causes.
2. Male or female subjects aged 18 to 75 years inclusive.
3. Must provide written informed consent for study-related procedures.
4. Must be capable of completing all study-related procedures, assessments, and visits in the judgment of Investigator.
5. Disease duration from ALS symptom onset of motor weakness ≤24 months.
6. ALSFRS-R total score ≥38 at screening visit.
7. ALSFRS-R Breathing subscore should be ≥9 at the time of screening.
8. ALSFRS-R Bulbar subscore should be ≥9 at the time of screening.
9. Forced vital capacity \>70% of predicted value.
10. PIFR ≥100 L/minute.
11. Must be receiving a stable dose of standard-of-care treatment Riluzole for 4-weeks before signing informed consent.
12. Female subjects who are of childbearing potential must agree to use of highly effective methods of contraception consistent with local regulations during the study, and for 3 months after the study drug administration. Examples include the following, but not limited to:

    1. Combined (estrogen and progestogen containing) or progestogen-only hormonal contraceptives;
    2. Intrauterine device or intrauterine hormone-releasing system; OR
    3. Post-menopausal status must have experienced their last menstrual period minimum of 1 year prior to study drug administration; OR
    4. Surgically sterilized. Female subject should be willing to not donate egg during the trial and for 3 months after the last dose of the study drug.
13. Male subjects who are sexually active with a female of childbearing potential must agree to use highly effective contraception as described above, or a combination of 2 acceptable methods of contraception (e.g., a barrier method along with a female partner using a hormonal contraceptive method), in accordance with local regulations, throughout the duration of the study, and for 3 months after the last dose of the study drug.

(Male subject should be willing to not donate sperm during the trial and for 3 months after the last dose of the study drug.)

Exclusion Criteria:

1. ALSFRS-R score change (decrease) by 2.5 or more points between the screening visit and Day 1 (baseline) score.
2. Bulbar onset ALS (\<9 bulbar subscore)
3. 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.
4. Any other significant neurological disorder which can interfere with study assessments, e.g., significant cognitive impairment and/or clinical dementia.
5. 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 the past year.
6. Severe cardiac disease (e.g., QTc\>500 ms), 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).
7. Any moderate-to-severe pulmonary disease or difficulty taking inhaled drugs.
8. Inability to tolerate the administration of an oral inhaled powder via DPI.
9. Has taken any investigational product within 30 days or 5 half lives of the drug, whichever is longer, prior to dosing.
10. Taking inhaled protein products on a chronic basis (such as insulin, parathyroid hormone, etc).
11. Subjects with a body weight of 32 kg or less, or a body mass index of \<17.5 or \>35.0 at time of screening.
12. Moderate-to-severe liver disease: aspartate aminotransferase (AST), alanine aminotransferase (ALT) \>3 times the upper limit of normal; total bilirubin \> 1.5 x ULN.; subjects with hepatic diseases such as hepatic cirrhosis, hepatic cancer and active hepatitis.
13. Moderate-to-severe renal disease: creatinine clearance \<45 mL/min/1.73 m2 (by Cockcroft-Gault calculation).
14. 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.
15. Pregnant or breast-feeding females.

Where this trial is running

Scottsdale, Arizona and 16 other locations

• Honor Health Neurology - Bob Bove Neuroscience Institute — Scottsdale, Arizona, United States (RECRUITING)
• University of California San Diego — La Jolla, California, United States (RECRUITING)
• Sutter Health - California Pacific Medical Center Research Institute — San Francisco, California, United States (RECRUITING)
• Mayo Clinic Jacksonville — Jacksonville, Florida, United States (RECRUITING)
• Lange Neurology — New York, New York, United States (RECRUITING)
• NEUROHK s.r.o. — Hradec Králové, Czechia (RECRUITING)
• Thomayer University Hospital - Fakultni Thomayerova nemocnice — Prague, Czechia (RECRUITING)
• Charité Centrum für Neurologie, Neurochirurgie und Psychiatrie — Berlin, Germany (RECRUITING)
• DIAKOVERE Henriettenstift - Klinik für Neurologie und Klinische Neurophysiologie — Hanover, Germany (RECRUITING)
• Universitaetsklinikum Schleswig-Holstein — Lübeck, Germany (RECRUITING)
• Michalski i Partnerzy Lekarze Spółka Partnerska — Krakow, Poland (RECRUITING)
• SP ZOZ Szpital Uniwersytecki w Krakowie — Krakow, Poland (RECRUITING)
• Centrum Medyczne NeuroProtect (NeuroProtect Medical Center) — Warsaw, Poland (RECRUITING)
• City Clinic Research — Warsaw, Poland (RECRUITING)
• University Clinical Center of Serbia — Belgrade, Serbia (RECRUITING)
• Hospital Universitario Vall D Hebron — Barcelona, Spain (RECRUITING)
• Hospital Universitario Ramon Y Cajal — Madrid, Spain (RECRUITING)

Study contacts

• Study coordinator: David R Elmaleh, PhD

Conditions: Amyotrophic Lateral Sclerosis, Lou Gehrigs Disease, ALS