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A Pilot Study of RNS60 in Amyotrophic Lateral Sclerosis (ALS)

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ClinicalTrials.gov Identifier: NCT02525471
Recruitment Status : Completed
First Posted : August 17, 2015
Last Update Posted : February 22, 2018
Sponsor:
Information provided by (Responsible Party):
Sabrina Paganoni, M.D., Massachusetts General Hospital

Brief Summary:
The purpose of this study is to determine the safety and tolerability of RNS60 in patients with Amyotrophic lateral sclerosis (ALS). Investigators will also measure the impact of RNS60 on several markers of neuro-inflammation, measured by blood biomarkers and positron emission tomography (PET) imaging.

Condition or disease Intervention/treatment Phase
ALS Drug: RNS60 Phase 1

Detailed Description:

Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative disease for which there is no cure. A substantial body of evidence implicates the neuroimmune system in ALS pathophysiology. Of relevance to this study, microglia activation in the brain has been found to correlate positively with faster rate of disease progression. In addition, studies of blood cells in people with ALS have shown an increased activation of two of the major inflammatory cell types in the body, monocytes and T cells. Among T cells, regulatory T cells (Tregs) have been recently proposed to play a role in ALS progression.

RNS60 is an electrokinetically altered aqueous fluid. Chemically, RNS60 is composed of saline and oxygen. The electrokinetic processing of RNS60 in Revalesio's patented Revalesio Pump (RP) produces charge-stabilized nanostructures (CSNs) that exhibit electrical fields. RNS60 is available for intravenous administration and inhalation. RNS60 has been extensively tested in preclinical toxicological studies and has shown very little to no side effects. In addition, RNS60 was well tolerated in three phase I human safety studies, one after intravenous administration and two after inhalation.

Preclinical in vitro and in vivo studies in multiple disease models have demonstrated that RNS60 has broad anti-inflammatory effects. These effects include reduction of microglia activation, increase of the Tregs subpopulation of lymphocytes, and neuroprotection in several disease models.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Study Start Date : October 2015
Actual Primary Completion Date : June 21, 2017
Actual Study Completion Date : October 18, 2017


Arm Intervention/treatment
Experimental: RNS60

Following screening visit to determine eligibility, enrolled subjects will undergo the baseline visit within 6 weeks where the first intravenous (IV) infusion of study medication, RNS60, will be administered. Study medication for inhalation use will be dispensed at this time, and again at weeks 7 and 15. Subjects will continue once a week follow ups to receive RNS60 by IV infusion, continuing inhalation use the remaining 6 days per week, for 24 weeks total. Additionally, eligible subjects will undergo PET imaging at baseline and again between weeks 18 and 23.

In addition, upon nearing completion of the core study, subjects will be given the option to continue to receive drug for approximately an additional 24 weeks, for a total of approximately 48 weeks on study drug, following the optional extension phase schedule of activities.

Drug: RNS60

RNS60 will be administered in two ways: by intravenous (IV) infusion one day a week (infusion dose: 375ml, infused over a 40-min period) and by inhalation (the remaining 6 days a week, 4 ml/day) for 24 weeks.

In addition, subjects will be given the option to continue to receive drug for approximately an additional 24 weeks, for a total of approximately 48 weeks on study drug. Study drug will be given by intravenous (IV) infusion one day a week (infusion dose: 375ml, infused over a 40-min period) and by inhalation (the remaining 6 days a week, 4 ml/day) during the extension phase.





Primary Outcome Measures :
  1. Safety as measured by the Number of Participants Experiencing Adverse Events [ Time Frame: 24 weeks ]
    Safety will be assessed by the occurrence of adverse events.

  2. Tolerability to Complete the Entire 24 Week Study on Study Drug [ Time Frame: 24 weeks ]
    Tolerability will be defined as the ability of subjects to complete the entire 24-week study on study drug.

  3. Blood biomarkers of inflammation. [ Time Frame: 24 weeks ]
  4. Neuroimaging biomarkers ([11C]-PBR28-Positron Emission Tomography (PET)) including both regions of interest and voxel-based analyses. [ Time Frame: 24 weeks ]
  5. Clinical outcome: Pulmonary Function, Measured by Slow Vital Capacity (SVC) [ Time Frame: 24 weeks ]
  6. Clinical outcome: Strength, Measured by Accurate Test of Limb Isometric Strength (ATLIS) [ Time Frame: 24 weeks ]
  7. Clinical outcome: Functional Status, Measured by Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) [ Time Frame: 24 weeks ]


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Amyotrophic Lateral Sclerosis (ALS) volunteers must be diagnosed as having possible, probable, probable-laboratory supported, or definite ALS, either sporadic or familial according to modified El Escorial criteria.
  • Age 18-80, able to provide informed consent, and comply with study procedures.
  • Participants must not have taken riluzole for at least 30 days, or be on a stable dose of riluzole for at least 30 days, prior to screening (riluzole-naïve participants are permitted in the study).
  • Women must not be able to become pregnant (e.g. post menopausal, surgically sterile, or using adequate birth control) for the duration of the study and 3 months after study completion.
  • Males should practice contraception for the duration of the study and 3 months after completion.
  • Ability to safely lie flat for 90 min for Positron Emission Tomography (PET) procedures in the opinion of the study physician.
  • High or mixed affinity to bind translocator (TSPO) protein (Ala/Ala or Ala/Thr)

Exclusion Criteria:

  • Abnormal liver function defined as aspartate aminotransferase (AST) and/or alanine transaminase (ALT) > 3 times the upper limit of the normal.
  • Renal insufficiency as defined by a serum creatinine > 1.5 times the upper limit of normal.
  • The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair ability of the participant to provide informed consent, according to PI judgment.
  • Clinically significant unstable medical condition (other than ALS) that would pose a risk to the participant if they were to participate in the study.
  • History of HIV, clinically significant chronic hepatitis, or other active infection.
  • Females must not be lactating or pregnant.
  • Active participation in another ALS clinical trial within 30 days of the Screening Visit
  • Exposure to immunomodulatory medications within 30 days of the Screening Visit.
  • Any contraindication to undergo MRI studies such as

    • History of a cardiac pacemaker or pacemaker wires
    • Metallic particles in the body
    • Vascular clips in the head
    • Prosthetic heart valves
    • Claustrophobia
  • Radiation exposure that exceeds the site's current guidelines
  • Current use of tobacco products including cigarettes, cigars, snuff and chewing tobacco, or nicotine replacement products such as gum or patch

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): NCT02525471


Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Sabrina Paganoni, M.D.
Investigators
Principal Investigator: Sabrina Paganoni, MD Massachusetts General Hospital
Principal Investigator: Nazem Atassi, MD Massachusetts General Hospital

Responsible Party: Sabrina Paganoni, M.D., Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02525471     History of Changes
Other Study ID Numbers: RNS60-01
First Posted: August 17, 2015    Key Record Dates
Last Update Posted: February 22, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Amyotrophic Lateral Sclerosis
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
TDP-43 Proteinopathies
Neuromuscular Diseases
Proteostasis Deficiencies
Metabolic Diseases