The Effect of RNS60 on ALS Biomarkers

Study Purpose:

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.

Disease:

Amyotrophic Lateral Sclerosis (ALS),  Familial ALS,  Sporadic ALS

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:

Enrolling

Phase:

Phase II

Study Chair(s)/Principal Investigator(s):

Ettore Beghi, MDIRCCS Istituto di ricerche farmacologiche Mario Negri di Milano

Clinicaltrials.gov ID (11 digit #):

NCT03456882

Neals Affiliated?

No

Coordinating Center Contact Information

IRCCS Istituto di ricerche farmacologiche Mario Negri di Milano
Ettore Beghi, MD / .(JavaScript must be enabled to view this email address) / 0039 02 39014542
Elisabetta Pupillo, PharmD, PhD / .(JavaScript must be enabled to view this email address) / 0039 02 39014605
Milano, Italy

Full Study Summary:

Study Sponsor:

Mario Negri Institute for Pharmacological Research

Participant Duration:

Estimated Enrollment:

142

Estimated Study Start Date:

11/18/2016

Estimated Study Completion Date:

04/30/2019

Posting Last Modified Date:

03/21/2018

Date Study Added to alsconsortium.org:

03/21/2018
  • Eligibility Criteria

    Gender:

    Female, Male

    Minimum Age:

    18

    Maximum Age:

    70

    Min Vital Capacity (% predicted normal):

    80

    Time since Symptom Onset:

    <24 months

    Time since Diagnosis:

    Can participants use Riluzole?

    Yes


    Inclusion Criteria:

    Age 18 through 70 years inclusive;
    Geographically accessible to the site and able to come to the site once a week for 24 weeks;
    Definite or probable 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:

    History of HIV, clinically significant chronic hepatitis, antecedent polio infection, or other active infection;
    Motor neuron disease (MND) other than ALS;
    Involvement of systems other than motor possibly determining a functional impairment (as measured by the end-points) for the entire duration of the study;
    Other severe clinical conditions (e.g., cardiovascular disorders, neoplasms) with impact on survival or functional disability in the next 12 months;
    Renal insufficiency as defined by a serum creatinine > 1.5 times the upper limit of normal;
    Poor compliance with previous treatments;
    Other experimental treatments in the preceding 3 months;
    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;
    Unwillingness or inability to take riluzole; 10) Poor capability to use an inhalation device;
    Abnormal liver function defined as AST and/or ALT > 3 times the upper limit of the normal.

  • Site Contact Information

    Massachusetts General Hospital
    Michael Doyle / .(JavaScript must be enabled to view this email address) / 617-724-7398
    Boston, Massachusetts 02114
    United States

    Ospedale San Raffaele
    Riva / 0226433838
    Miano,
    Italy

    Centro Clinico NEMO - Fondazione Serena Onlus
    Lunetta / 02 914 3371
    Milano,
    Italy