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The Effect of RNS60 on ALS Biomarkers (RNS60)

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ClinicalTrials.gov Identifier: NCT03456882
Recruitment Status : Recruiting
First Posted : March 7, 2018
Last Update Posted : June 8, 2018
Sponsor:
Collaborators:
ALS Association
Get out ONLUS
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research

Brief 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.


Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: RNS60 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 142 participants
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.
Primary Purpose: Other
Official Title: The Effect of RNS60 on ALS Biomarkers
Actual Study Start Date : November 18, 2016
Estimated Primary Completion Date : April 30, 2019
Estimated Study Completion Date : April 30, 2019


Arm Intervention/treatment
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.
Drug: RNS60
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).

Drug: RNS60
normal saline plus oxigen in nanobubble




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. Survival [ Time Frame: up to 24 weeks ]
    2. The preliminary efficacy of RNS60 in prolonging survival (or time to tracheostomy, whichever comes first);

  3. 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

  4. 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

  5. Quality of life [ 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18 through 70 years inclusive;
  2. Geographically accessible to the site and able to come to the site 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;

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.

Information from the National Library of Medicine

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


Contacts
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Contact: Ettore Beghi, MD 0039 02 39014542
Contact: Elisabetta Pupillo, PharmD, PhD 0039 02 39014605 rns60@marionegri.it

Locations
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United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Sabrina Paganoni    617-726-2000      
Contact: Michael Doyle    617-724-7398    mdoyle16@mgh.harvard.edu   
Italy
Azienda Opsedaliera Universitaria Consorziale Policlinico- Università degli studi di Bari Recruiting
Bari, Italy
Contact: Simone    080 559 1111      
Spedali civili di Brescia Recruiting
Brescia, Italy
Contact: Filosto    030 39951      
ASST Valle Olona Presidio ospedaliero Gallarate Withdrawn
Gallarate, Italy
IRCCS Azienda Ospedaliera Universitaria San Martino IST Recruiting
Genova, Italy
Contact: Caponnetto    0105551      
Ospedale San Raffaele Recruiting
Miano, Italy
Contact: Riva    0226433838      
Centro Clinico NEMO - Fondazione Serena Onlus Recruiting
Milano, Italy
Contact: Lunetta    02 914 3371      
Presidio Ospedaliero Provinciale - Nuovo Ospedale Civile "S. Agostino Estense" Recruiting
Modena, Italy
Contact: Mandrioli    059435111      
Azienda Ospedaliera Universitaria della Seconda Univ. Degli Studi di Napoli (AOU-SUN) Recruiting
Napoli, Italy
Contact: Monsurrò    800177780      
Azienda Ospedaliero Universitaria Maggiore della Carità Recruiting
Novara, Italy
Contact: Mazzini    03213731      
Azienda Ospedaliera di Padova-Università degli studi di Padova Recruiting
Padova, Italy
Contact: Sorarù    0498211111      
Azienda Ospedaliera Universitaria Policlinico "P Giaccone" Recruiting
Palermo, Italy
Contact: La Bella    091 655 1111      
Istituto Neurologico Nazionale "C. Mondino" Recruiting
Pavia, Italy
Contact: Ceroni    0382 3801      
Azienda Ospedaliero-Universitaria Pisana Active, not recruiting
Pisa, Italy
POLICLINICO UMBERTO I - Università di Roma "La Sapienza" Not yet recruiting
Roma, Italy
Contact: Inghilleri    0649971      
IRCCS Casa sollievo della Sofferenza Recruiting
San Giovanni Rotondo, Italy
Contact: Zarrelli    0882 410111      
Azienda Ospedaliera Universitaria Senese (AOUS) Recruiting
Siena, Italy
Contact: Giannini    0577 767676      
Azienda Ospedaliera "Santa Maria" di Terni Recruiting
Terni, Italy
Contact: Spera    0744 2051      
Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino. Not yet recruiting
Torino, Italy
Contact: Chiò    011 633 1633      
Azienda Ospedaliera "Card. G. Panico" Not yet recruiting
Tricase, Italy
Contact: Logroscino    0833 773111      
Sponsors and Collaborators
Mario Negri Institute for Pharmacological Research
ALS Association
Get out ONLUS
Investigators
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Study Chair: Ettore Beghi, MD IRCCS Istituto di ricerche farmacologiche Mario Negri di Milano

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Responsible Party: Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier: NCT03456882     History of Changes
Other Study ID Numbers: RNS60
First Posted: March 7, 2018    Key Record Dates
Last Update Posted: June 8, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Mario Negri Institute for Pharmacological Research:
AMYOTROPHIC LATERAL SCLEROSIS
RNS60
Biomarkers
clinical trial
therapy

Additional relevant MeSH terms:
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RNS60
Sclerosis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Pharmaceutical Solutions