The Effect of RNS60 on ALS Biomarkers
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Intervention: RNS60
Intervention description: normal saline plus oxigen in nanobubble
Intervention MeSH terms: RNS60
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Multicenter, randomized, double-blind, placebo-controlled, parallel group, add-on phase II trial. ALS Patients who meet the study's inclusion/exclusion criteria and sign the Informed Consent Form will be enrolled. A total of 142 subjects will be randomly assigned to receive treatment with either RNS60 or placebo while concomitantly taking riluzole (50 mg tablet t.i.d.). RNS60 or placebo will be administered intravenously once a week as well as inhaled via nebulization every morning in the remaining six days of each week for 24 weeks. Blood samples for biomarker analysis will be collected on day 1, week 4, w12, and w24. Safety and preliminary efficacy will be assessed by way of physical exam, vital signs and AEs. Changes in disability and quality of life will be assessed using the ALSFRS-R scale, FVC and ALSAQ-40 scale. Each patient will be followed up for a maximum period of 48 weeks (24-week treatment + 24-week follow up) or until death or tracheostomy, whichever occurs first.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Double blinde study.
Enrollment: 147.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: AMYOTROPHIC LATERAL SCLEROSIS; RNS60; Biomarkers; clinical trial; therapy

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.
    

Eligibility 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.