Phase IIB Study of PHENOGENE-1A (Cromolyn) as an Adjuvant Therapy in Mild to Moderate ALS

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Phenonet Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

27 Jan 2026 → ongoing

Decision date (initial)

2025-10-22

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

PhenoNet, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Dose response, Safety

To evaluate the effects of PHENOGENE-1A (cromolyn) on functional changes in subjects with mild to moderate stage ALS disease, by using the ALSFRS-R to measure changes in the score, over a 24-week treatment period.

Secondary objectives 4

1. To evaluate the effects of PHENOGENE-1A (cromolyn) on functional changes in subjects with mild to moderate stage ALS disease, by using the Combined Assessment of Function and Survival (CAFS) after a 24 week treatment period has been completed.
2. To evaluate the time from randomization to the first of 7 consecutive days on which permanent assisted ventilation (either invasive or non-invasive) was used for >22 hrs/day as a direct consequence of symptom progression related to ALS.
3. To evaluate the effects of PHENOGENE-1A on respiratory changes in subjects with mild to moderate stage ALS disease, by measuring changes in percent predicted forced vital capacity (%FVC) Predicted Value, over a 24-week treatment period.
4. To measure the changes in peak inspiratory flow rate (PIFR) over a 24-week treatment period.

Conditions and MedDRA coding

Amyotrophic Lateral Sclerosis (ALS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 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.
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 1).
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. FVC >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: 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.
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 15

1. ALSFRS-R score change (decrease) by 2.5 or more points between the Screening 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 (IP) 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 [PTH], etc).
11. 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.
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 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
15. Pregnant or breast-feeding females.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Absolute change in ALSFRS-R total score from baseline to Week 24.

Secondary endpoints 4

1. Mean rank for CAFS across all by treatment group at Week 24.
2. Time to event requiring full-time or nearly full-time respiratory support.
3. Mean change in %FVC from baseline to Week 24.
4. Mean change in PIFR from baseline to Week 24.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Phenonet Inc.

Sponsor organisation

Phenonet Inc.

Address

23 Juniper Lane

City

Newton

Postcode

02459-2839

Country

United States

Scientific contact point

Organisation

Phenonet Inc.

Contact name

Chairman

Public contact point

Organisation

Phenonet Inc.

Contact name

Chairman

Third parties 8

Locations

4 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 43 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications