The Effect of RNS60 on ALS Biomarkers (RNS60)
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|ClinicalTrials.gov Identifier: NCT03456882|
Recruitment Status : Active, not recruiting
First Posted : March 7, 2018
Last Update Posted : December 8, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Amyotrophic Lateral Sclerosis||Drug: RNS60||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||142 participants|
|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.|
|Official Title:||The Effect of RNS60 on ALS Biomarkers|
|Actual Study Start Date :||November 18, 2016|
|Actual Primary Completion Date :||April 30, 2020|
|Estimated Study Completion Date :||May 30, 2021|
Active Comparator: RNS60
RNS60 for injection, i.e. in the IV bags, is produced using 0.9% Sodium Chloride for injection. RNS60 for inhalation, i.e. in the syringes, is produced using 0.9% Sodium Chloride for irrigation. Syringes and IV bags are to remain refrigerated at 2 to 8°C (36 to 46°F) when not in use. RNS60 meets its stability specification for 12 months.
normal saline plus oxigen in nanobubble
Placebo Comparator: NORMAL SALINE
Normal saline (NS) for injection, i.e. in the IV bags, is packaged 0.9% Sodium Chloride for injection. NS for inhalation, i.e. in the syringes, is packaged 0.9% Sodium Chloride for irrigation. NS does not require refrigerated storage for use. However, for blinding purposes refrigeration is required before distributing to subjects. NS meets stability specifications for 24 months.
RNS60 has been tested in three Phase I safety studies, NCT01264783, NCT01057498, and NCT01511302 in the USA, and a Phase IIa (NCT02422121) study in UK without any safety concern. Two other Investigator initiated Phase IIa trials are currently ongoing, one in Mass General Hospital (NCT02525471), and one in the University of Zurich (with University of Innsbruck as a second site).
normal saline plus oxigen in nanobubble
- Pharmacodynamic biomarkers [ Time Frame: up to 24 weeks ]1. 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.
- ALSFRS-R scale [ Time Frame: up to 24 weeks ]1. The preliminary efficacy of RNS60 on functional disability, as measured by the Amyotrophic Lateral Sclerosis Funcional Rating Scale-Revised (ALSFRS-R scale). minimum score: 0 maximum score: 48 higher values represent a better outcome
- Survival [ Time Frame: up to 24 weeks ]2. The preliminary efficacy of RNS60 in prolonging survival (or time to tracheostomy, whichever comes first);
- Forced Vital Capacity (FVC) [ Time Frame: up to 24 weeks ]3. The preliminary efficacy of RNS60 in slowing the decline of forced vital capacity (FVC) from baseline minimum score: 0 maximum score: none higher values represent a better outcome
- Incidence of adverse event (Tolerability) related to RNS60 [ Time Frame: up to 24 weeks ]4. The tolerability and safety of RNS60 through the identification of unexpected adverse events
- Quality of life (ALSAQ-40) scale [ Time Frame: up to 24 weeks ]5.The impact of RNS60 on quality of life as measured by Amyotrophic Lateral Sclerosis Assessment Questionnaire 40 questions (ALSAQ-40) scale minimum score: never maximum score: often single item will be evaluate
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03456882
|Study Chair:||Ettore Beghi, MD||IRCCS Istituto di ricerche farmacologiche Mario Negri di Milano|