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

Brief Title

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


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.
    

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 Phase

Phase 1

Study Type

Interventional


Primary Outcome

Safety as measured by the Number of Participants Experiencing Adverse Events


Condition

ALS

Intervention

RNS60

Study Arms / Comparison Groups

 RNS60
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

24

Start Date

October 2015

Completion Date

October 18, 2017

Primary Completion Date

June 21, 2017

Eligibility 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
      

Gender

All

Ages

18 Years - 80 Years

Accepts Healthy Volunteers

No

Contacts

Sabrina Paganoni, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02525471

Organization ID

RNS60-01


Responsible Party

Sponsor-Investigator

Study Sponsor

Sabrina Paganoni, M.D.


Study Sponsor

Sabrina Paganoni, MD, Principal Investigator, Massachusetts General Hospital


Verification Date

February 2018