Evaluation of Sodium Cromoglicate as an Adjuvant Therapy in Mild to Moderate Amyotrophic Lateral Sclerosis: A Phase IIb Randomized, Double-Blind, Placebo-Controlled Study
- Trial ID
- 2025-520688-42-00
- Protocol
- PHENOALS-001
- Sponsor
- Phenonet Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate the effects of cromolyn on functional changes in subjects with mild to moderate amyotrophic lateral sclerosis (ALS) using the ALSFRS-R score over a 24-week treatment period. 5
Secondary objectives include:
- Evaluation of functional changes using the Combined Assessment of Function and Survival (CAFS) after 24 weeks.
- Assessment of the time from randomization to the initiation of permanent assisted ventilation, defined as either invasive or non-invasive use for more than 22 hours per day due to symptom progression.
- Measurement of respiratory changes via the percent predicted forced vital capacity (%FVC).
- Evaluation of changes in the peak inspiratory flow rate (PIFR) throughout the 24-week period.
Participants
This study involves 32 participants diagnosed with Amyotrophic Lateral Sclerosis. The study population includes both male and female patients ranging from 18 to 75 years of age. Eligible individuals must have a disease duration of motor weakness not exceeding 24 months since symptom onset. Participants are required to have a forced vital capacity greater than 70% of the predicted value and a forced inspiratory vital capacity of at least 100 L/minute. Clinical requirements include an ALSFRS-R total score of 38 or higher, with respiratory and bulbar subscores of at least 9. Subjects must be on a stable dose of riluzole for four weeks prior to enrollment. Specific contraception requirements are established for individuals of childbearing potential to manage reproductive risks during and after the treatment period.
Plans and Procedures
This Phase IIb, randomized, double-blind, placebo-controlled study is designed to evaluate the effects of PHENOGENE-1a (sodium cromoglicate) as an adjuvant treatment in subjects with mild to moderate Amyotrophic Lateral Sclerosis (ALS). The investigation focuses on functional changes over a 24-week treatment period. The methodology includes a screening visit to confirm diagnosis according to the revised El Escorial Criteria and to verify specific clinical parameters, such as a forced vital capacity (FVC) greater than 70% of the predicted value and specific ALSFRS-R scores. Participants will be administered either the active inhalation powder or a placebo via a dry powder inhaler (DPI). The primary endpoint is the absolute change in the ALSFRS-R total score from baseline to week 24. The study involves a sequence of clinical assessments and follow-up visits to monitor efficacy and safety through the end-of-study period. Subject involvement is determined by the 24-week treatment duration, though participation may be subject to early termination based on investigator judgment or clinical requirements.
Treatment
The experimental medication, PHENOGENE-1a, consists of sodium cromoglicate. This substance is administered as an inhalation powder contained within a hard capsule. The dosage is 64.8 mg, which is delivered via the inhalation route.
The control group receives a placebo administered through oral inhalation using a dry powder inhaler (DPI).
Efficacy
The efficacy of PHENOGENE-1a in subjects with mild to moderate amyotrophic lateral sclerosis is evaluated through several primary and secondary endpoints. The primary endpoint is the absolute change in the ALSFRS-R total score from baseline to Week 24.
Secondary efficacy assessments include:
- The mean rank for CAFS across treatment groups at Week 24.
- The time to event requiring full-time or nearly full-time respiratory support.
- The mean change in %FVC from baseline to Week 24.
- The mean change in PIFR from baseline to Week 24.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Diagnosis of ALS; subjects must have a diagnosis of ALS according to the revised El Escorial Criteria as follows: a) Evidence of lower motor neuron (LMN) degeneration by clinical, electrophysiological, or neuropathological examination. b) Evidence of upper motor neuron (UMN) degeneration by clinical examination. c) Progressive spread of symptoms or signs within a region or to other regions, as determined by clinical examination or the history of disease progression. d) Absence of electrophysiological, neuroimaging, or pathological evidence of other diseases that might explain the UMN or LMN degeneration and exclusion of other causes.
- Male or female subjects aged 18 to 75 years inclusive.
- Must provide written informed consent for study-related procedures.
- Must be capable of completing all study-related procedures, assessments, and visits in the judgment of Investigator.
- Disease duration from ALS symptom onset of motor weakness ≤24 months.
- ALSFRS-R total score ≥38 at screening (Visit 1).
- ALSFRS-R Breathing subscore should be ≥9 at the time of screening.
- ALSFRS-R Bulbar subscore should be ≥9 at the time of screening.
- FVC >70% of predicted value.
- PIFR ≥100 L/minute.
- Must be receiving a stable dose of standard-of-care treatment, Riluzole for 4-weeks before signing informed consent.
- 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: a) Combined (estrogen and progestogen containing) or progestogen-only hormonal contraceptives; b) Intrauterine device or intrauterine hormone-releasing system; OR c) Post-menopausal status must have experienced their last menstrual period minimum of 1 year prior to study drug administration; OR d) 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.
- 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
- ALSFRS-R score change (decrease) by 2.5 or more points between the Screening and Day 1 (baseline) score.
- Bulbar onset ALS (<9 bulbar subscore).
- 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 the past year.
- 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).
- Any moderate-to-severe pulmonary disease or difficulty taking inhaled drugs.
- Inability to tolerate the administration of an oral inhaled powder via DPI.
- Has taken any investigational product (IP) within 30 days or 5 half-lives of the drug, whichever is longer, prior to dosing.
- Taking inhaled protein products on a chronic basis (such as insulin, parathyroid hormone [PTH], etc).
- Subjects with a body weight of 32 kg or less, or a body mass index (BMI) of <17.5 or >35.0 at time of screening.
- 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.
- Moderate-to-severe renal disease: creatinine clearance <45 mL/min/1.73 m2 (by Cockcroft- Gault calculation).
- Any CS 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Czechia | Recruiting | 01 Nov 2025 | 17 |
 Germany | Recruiting | 01 Nov 2025 | 36 |
 Poland | Recruiting | 01 Nov 2025 | 45 |
 Spain | Recruiting | 01 Nov 2025 | 30 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
PHENOGENE-1a | Test | INHALATION POWDER, HARD CAPSULE | INHALATION USE | 64.8 | 24 | PRD12405328 |
Placebo capsule, oral inhalation via DPI | Placebo | N/A | — | — | — | N/A |