The Effect of RNS60 on ALS Biomarkers

• Status: Completed
• Trial end date: 2021-05-30
• Target enrollment: 0
• Participant gender: All

Summary

Amyotrophic Lateral Sclerosis (ALS) is a rare lethal neurodegenerative disease involving inflammation. Riluzole, the only drug for ALS, improves median survival by 3 months. This prompts new treatments of ALS. RNS60 is an experimental drug with favorable effects in preclinical studies of neuroinflammation and neurodegeneration. Based on significant efficacy demonstrated in preclinical studies and its excellent clinical safety profile, RNS60 is a promising candidate for a drug to treat ALS. Developing a pharmacodynamic marker will be a first and important step for dose finding and exploration of the mechanism of action in human, and pave the way to trials measuring drug efficacy.

The Investigator propose a multicenter, randomized, double-blind, placebo-controlled, parallel group, Phase II trial. The study centers will be located in Italy and at Massachusetts General Hospital (MGH) in Boston. A total of 142 ALS patients will be randomly assigned to RNS60 or placebo (administered by intravenous infusion once/week and inhaled via nebulization every morning for 24 weeks). All participants will also take riluzole (50-mg tablet twice/day). Blood samples for biomarker analysis (protein, RNA) will be collected in the screening period, on day 1, week 4,12 and 24. Both safety and potential therapeutic effects of RNS60 will be also assessed.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mario Negri Institute for Pharmacological Research
• Collaborators: ALS Association; Get out ONLUS
• Treatments: RNS60

Criteria

Inclusion Criteria:

1. Age 18 through 80 years inclusive;

2. Geographically accessible to the site and able to come to the site once a week for 24 weeks;

3. Definite, probable, probable laboratory supported ALS diagnosis according to the revised El Escorial criteria; 4) Disease duration 6 to 24 months from symptom onset;

5) Self sufficiency: Satisfactory bulbar and spinal function (score 3+ on the ALSFRS-R for swallowing, cutting food and handling utensils, and walking); 6) Satisfactory respiratory function (FVC ≥80% of predicted); 7) Documented progression of symptoms in the last three months, as measured by the ALSFRS-R scale; 8) Ability to understand and comply with the study requirements and to give written informed consent personally or via a legally authorized representative; 9) Treatment with riluzole 50 mg twice/day for at least 1 month prior to screening visit.

Self sufficiency: this term reflect independence in daily living activities. It is an intuitive parameter to indicate preservation of key functional activities, and - not least

• it has shown to be a valid and reliable measure

Exclusion Criteria:

1. History of HIV, clinically significant chronic hepatitis, antecedent polio infection, or other active infection;

2. Motor neuron disease (MND) other than ALS;

3. Involvement of systems other than motor possibly determining a functional impairment (as measured by the end-points) for the entire duration of the study;

4. Other severe clinical conditions (e.g., cardiovascular disorders, neoplasms) with impact on survival or functional disability in the next 12 months;

5. Renal insufficiency as defined by a serum creatinine > 1.5 times the upper limit of normal;

6. Poor compliance with previous treatments;

7. Other experimental treatments in the preceding 3 months;

8. Women who are lactating or able to become pregnant (e.g. who are not post menopausal, surgically sterile, or using inadequate birth control) and men unable to practice contraception for the duration of the treatment and 3 months after its completion;

9. Unwillingness or inability to take riluzole; 10) Poor capability to use an inhalation device;

10. Abnormal liver function defined as AST and/or ALT > 3 times the upper limit of the normal.