Amyotrophic Lateral Sclerosis MedDRA version: 21.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.1 Level: LLT Classification code 10052889 Term: ALS System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: RNS60
Product Code: RNS60
Pharmaceutical Form: Solution for infusion
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use
Pr
Sponsors
IRCCS- ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Age 18 through 70 years inclusive; 2) Geographically accessible to the site and able to come to the site center once a week for 24 weeks; 3)Definite or probable ALS diagnosis according to the revised El Escorial criteria; 4) Disease duration 6 to 24 months from symptom onset to study entry; 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 (decrease of at least one point); 8) Ability to understand and comply with the study requirements; 9) Ability to give written informed consent personally or, as an alternative, via a legally authorized representative; 10) Treatment with riluzole 50 mg twice/day for at least 1 month prior to screening visit. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 112 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
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 other systems 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 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 compliance with an inhalation device; 11) Abnormal liver function defined as AST and/or ALT > 3 times the upper limit of the normal.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To measure the effect of RNS60 treatment on selected pharmacodynamic biomarkers in ALS patients concurrently treated with riluzole. Candidate markers include: 1. T-reg (measured via FOXP3 and CD25 mRNA); 2. Cyp-A; 3. 3-NT; 4. Actin-NT; 5. MCP-1; 6. IL-17.;Secondary Objective: 1.The preliminary efficacy of RNS60 on functional disability, as measured by the ALSFRS-R scale; 2.The preliminary efficacy of RNS60 in prolonging survival (or time to tracheostomy, whichever comes first); 3.The preliminary efficacy of RNS60 in slowing the decline of forced vital capacity (FVC) from baseline; 4.The tolerability and safety of RNS60 through the identification of unexpected adverse events; 5.The impact of RNS60 on quality of life as measured by ALSAQ-40 scale. ;Primary end point(s): The mean change over time in the proportion of T-reg (measured via FOXP3 and CD25 mRNA); the mean change over time in the plasma concentrations of Cyp-A, 3-NT, Actin-NT, MCP-1, IL-17 in the two treatment arms, during the entire treatment period (from baseline to 24 weeks).;Timepoint(s) of evaluation of this end point: from baseline to 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The mean change in the proportion of T-reg (measured via FOXP3 and CD25 mRNA); the mean change over time in the plasma concentrations of Cyp-A, 3-NT, Actin-NT, MCP-1, IL-17 during the follow up period ; The cumulative proportion of subjects becoming no longer self-sufficient at 4, 12, 24, 36 and 48 weeks in the two treatment arms (defined as those scoring 2 or lower on at least one of the ALSFRS-R items for swallowing, cutting food and handling utensils, or walking); The mean change of ALSFRS-R total score in the two treatment arms ; The cumulative proportion of deaths or tracheostomies in the two treatment arms ; The mean change of FVC score in the two treatment arms ; The total number of subjects in the two treatment arms experiencing at least one AE leading to treatment discontinuation ; The mean number of AEs per treatment arm ; The mean change of ALSAQ-40 score measuring quality of life ;Timepoint(s) of evaluation of this end point: from 24 to 48 weeks; weeks 4, 12, 24, 36 and 48; during the treatment and follow up period; during the entire study including follow-up; during the treatment and follow up period; Weeks N 4, 12 and 24; Weeks N 4,12 e 48 ; at the completion of the treatment and follow up period | — |
Countries
Italy, United States
Contacts
Public ContactLaboratorio di malattie neurologich
IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Milano
Outcome results
None listed