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

Prior treatment

• Has taken any investigational product (IP) within 30 days or 5 half-lives of the drug, whichever is longer, prior to dosing.

Other illness

• 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.
• Any moderate-to-severe pulmonary disease or difficulty taking inhaled drugs.

Lab values

• 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
• 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).

Other

• ALSFRS-R score change (decrease) by 2.5 or more points between the Screening and Day 1 (baseline) score.
• 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.
• Pregnant or breast-feeding females.
• 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.
• Inability to tolerate the administration of an oral inhaled powder via DPI.

• 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.
• 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.
• 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.