Investigational ALS Treatment NPT520-34 Begins Phase 1 Trial in Healthy Volunteers

Investigational ALS Treatment NPT520-34 Begins Phase 1 Trial in Healthy Volunteers

NPT520-34, an investigational small molecule for the treatment of Parkinson’s disease and amyotrophic lateral sclerosis (ALS), is being tested on healthy individuals in a new Phase 1 clinical trial, its developer Neuropore Therapies has announced.

Brain inflammation is a common feature among many neurodegenerative disorders, including Parkinson’s, Alzheimer’s disease, and ALS. For that reason, there has been an increasing interest in therapies that are able to minimize or prevent neuroinflammation.

NPT520-34 has been shown to reduce the levels of brain inflammation markers and toxic proteins in the central nervous system (CNS, which comprises the brain, brainstem, and cerebellum) of animal models of Parkinson’s, Alzheimer’s, and ALS.

The compound is administered orally, and is small enough to be able to cross the blood-brain barrier, a highly selective, semipermeable membrane that isolates the brain from the blood that circulates in the body.

NPT520-34’s safety, tolerability, and pharmacokinetic properties are now being tested in up to 48 healthy volunteers participating in a single-center Phase 1 clinical trial. (Pharmacokinetics studies how a drug is absorbed, distributed, metabolized, and eliminated from the body.)

“We are excited to start the Phase 1 clinical trial with NPT520-34 which represents Neuropore’s second therapeutic candidate to enter clinical development. We have extensively studied NPT520-34 in several transgenic animal models of neurodegenerative diseases, including [Parkinson’s disease], ALS and Alzheimer’s disease,” Errol De Souza, PhD, president and CEO of Neuropore, said in a press release.

“We are encouraged by the broad and robust effects seen in animal models including decreases in markers of brain neuroinflammation (microglial and astrocytic activation) and decreases in neurotoxic misfolded proteins (for example, alpha-synuclein for Parkinson’s, superoxide dismutase 1 for ALS, and beta-amyloid for Alzheimer’s),” he added.

The trial will have two distinct phases: an initial single-dose ascending phase, in which NPT520-34 will be administered at a single dose in all participants, with the possibility of incremental adjustments; and a second multiple-ascending dose phase, in which the compound will be administered at different doses, again with the possibility of incremental adjustments.

The study’s primary objective will be to assess the safety, tolerability and pharmacokinetic properties of single and multiple doses of the compound. The pharmacokinetic properties of a capsule formulation of NPT520-34 taken with and without food, will be tested separately in another group of healthy subjects. Exploratory outcomes will include the assessment of blood biomarkers indicative of therapy success.

Phase 1 trials assessing the properties of NPT520-34 in patients with neurodegenerative disorders should start in 2020.

“We believe NPT520-34 represents a promising new small molecule therapeutic opportunity for patients with severe unmet needs,” De Souza said.

13 comments

    • Joana Carvalho says:

      Hi Barbara. This trial is only meant for healthy volunteers to assess the safety of the treatment. If all goes well, trials in patients should start next year. By then there shall be information on how patients may enroll in the trial.

      • I am coming up on my two anniversary with ALS and I may not have another year. I am positive person who has daily struggles with my abuser. Everyday I have to adapt and think outside of the box to do everyday tasks. I live alone. I don’t understand why healthy people are used. We are already dying, what do we have to lose. With the accelerometers, voice recordings, database with genetics, lifestyle, demographics used by ALS Therapy Institute/ Precision Medicine you can track the progression of patients. I donate skin, blood, fecal, genital nasal, urine samples. Donating my body to research when my life ends. Researchers have had over 100 years and millions of dollars to find cure. But you exclude people with als because of age or because we minimally use a bi pap to try to prolong our life. I want to see my Sons get married next year. I want to see my Grandchild that will born next year. I fight *** everyday and am denied assistance I need and denied by clinical trials. I know patients enter trials – some do not live to end of trial. I know sometimes you have trials that you cannot fill. Think outside of the box and find a better way to conduct trials. This method has not worked for 100 years and needs to be revised. I only allow myself a 10 minutes to vent my negative feelings. You got to join me in my allowed time today. I speak for all *** patients. I had to take money out of my food allowance to make a donation for research. But I want a cure found before another family member of mine has to suffer with ***. I read patients comments on various websites. You are letting us down. We are losing hope. I do not doubt you are dedicated to find cure. But if we could exchange places for just one day I guess we could understand each other better. But then you would not to live one day in my shoes. I am tired of being told NO and promising research in the future What will take it?

  1. Dan D Montgomery says:

    I’ve begged my VA doctor to get me into one of the many clinical trials for ALS treatment but he failed me. I’ve contacted several clinical trials myself but have been refused treatment for dumb reasons like my diagnosis was more than 2 years ago, my breathing is too weak or that I am just too old. I have tried to invoke the Right-To-Try Law and access treatment from drug companies like BrainStorm for NurOwn but they denied my request. All the new cure money seems to be pouring into Mouse Clinical Trials. Mice! The Rats are getting the better treatment and all the $$$$’s from our donations while I lay here getting weaker and weaker.

    ~Dreams Flame Out~

    I’m watchin’ my dreams flame out
    As clinical trial requests get turned down
    I’m so on fire this ALS hurts like hell
    Watchin’ all my dreams just flame out

    Just watchin’ rivers run
    Down the IV tube into my vein
    It’s almost like it’s cryin’ my tears
    I had the world on a string
    And then I lost everything
    That’s how I wound up here

    Watchin’ my dreams flame out
    As clinical trial requests get turned down
    There’s nothing left but an empty heart now
    It’s all memories now
    Smokin’ memories that ain’t nothin’ but ashes
    In the no cure low lights
    It’s done me wrong so tempt me so right
    I’m so on fire this ALS hurts like hell
    As all my dreams just flame out

    If you put your hands on the ALS flame
    You’ve got no right to complain
    ‘Cause you know it’s gonna leave a mark
    When the glow comes to an end
    Like scattered embers in the wind
    Means you’re lookin’ for a brand new spark

    Watchin’ my dreams flame out

    Clinical trials I cant get
    I’m gonna quit
    But who am I kiddin’ I just can’t lay down
    So I keep hangin’ around

    Watchin’ my dreams flame out
    As clinical trial requests get turned down
    There’s nothing left but an empty heart now
    It’s all memories now
    Smokin’ memories that ain’t nothin’ but ashes
    In the no cure low lights
    It’s done me wrong so tempt me so right
    I’m so on fire this ALS hurts like hell
    As all my dreams just flame out
    I’m so on fire this ALS hurts like hell
    As all my dreams just flame out

    • Randy says:

      The clinical trials are so unfair. Less than 40% get into the trials because most don’t meet the criteria. Were is all of the money going??? It should be investigated.

  2. Mike Earl says:

    @Dan

    Your comment moved me, I have many of the same feelings you do.
    Sad that many of us can’t get a chance to try some of this treatments, getting worse all the time and would rather they experiment on willing volunteers who don’t have much too lose. I want the option for myself to try some of this treatments before it’s too late!

  3. Robert Ferson says:

    I lost my wife to ALS two years ago and have a great desire to help with any research looking for a treatment. Could I be considered as a participant in this study?

    • Joana Carvalho says:

      Hi Robert. I am so sorry for your loss. Possibly. Where are you from? As of now the trial is only recruiting patients in the U.S.
      Here you can find more information about the trial, including the eligibility criteria, recruitment sites and also the contacts of the researchers carrying out the study:
      https://clinicaltrials.gov/ct2/show/NCT03954600

  4. Mauro Maesa says:

    Come diceva il grande poeta Alessandro Manzoni in una sua famosa poesia sulla morte di Napoleone: “Ai posteri l’ardua sentenza!”. Beato chi la vede, la fine di questa sperimentazione!

  5. David Loar says:

    Hi Everyone,

    I know it’s really frustrating to feel (or be) excluded from a study with a promising new drug. All I can really say is…this is the very very first Phase of clinical testing in adult humans for this novel therapeutic. The last mammal this drug was tested in was mice.

    Remember, the purpose of a Phase I clinical trial is to demonstrate that it’s safe enough and well-tolerated enough in a ‘healthy’ population with minimal variability between participants, so that it can eventually be approved for Phase II. This Phase I trial is designed by the FDA to assess the safety (pharmacovigilance), tolerability, pharmacokinetics, and pharmacodynamics of a drug. Phase I trials usually include dose-ranging/dose escalation, so that the safest dose can be found and to discover the point at which a compound is too poisonous to administer. In other words, for your own safety & for the reliability of the trial data…it’s not appropriate or even safe to test a “first in human” drug on those suffering from ANY disease–let alone the disease the drug is designed to treat.

    The single reason they test in healthy subjects in Phase I is to reduce data variance…because ANY variability in tolerance, metabolism, adverse side effects, protein interactions, etc will ruin the data. Imagine testing Morphine in only 45 patients…some were children with no tolerance…some were addicts with high tolerance…some were already taking stimulants…some were already taking depressants…some were allergic to naturally occurring opiates…and some had a recent traumatic brain injury. The data would tell you absolutely nothing. Instead, you’d test the drug in healthy adults to see if there is any appreciable toxicity compared to a placebo. Phase Ia & Ib don’t even test if the drug actually works. They literally only test if they’re safe to ingest.

    If they’re safe, Phase II will increase the sample population because Phase II data requires the use of more statistical data analysis (which requires larger populations). Phase IIa studies are usually pilot studies designed to demonstrate clinical efficacy or biological activity. In other words…is NPT520-34 actually effective in reducing aggregated alpha-synuclein and lewy body dementia? Will it help reduce neural inflammation in patients with ALS or PD or AD? Which of these 3 conditions does it have the highest statistical significance in treating. In biostats, this is called a t-test…does the patient population receiving the drug do better than the patient population receiving placebo? If yes…then it’s on to Phase IIb.

    Phase IIb studies look to find the optimum dose at which the drug shows biological activity with the least side-effects. In biostats, this is called ANOVA. Now that you’ve determined the drug does, indeed, work the way it was expected at a statistically significant rate to justify the possibility of marketing it, what is the best dose? Is there a best dose? For Phase IIb, they would compare the statistical differences between (for example…) the placebo group, the 5mg group, the 10mg group, and the 20mg group. Sometimes the 5mg will have the most biologically significant results AND be the safest. Sometimes 5mg is good, 10mg is better, but 20mg is actually worse.

    Perhaps to truly address all these frustrations…it’s important to understand efficacy vs. effectiveness:

    When a study assesses efficacy, it is looking at whether the drug given in the specific manner described in the study is able to influence an outcome of interest (e.g. tumor size) in the chosen population (e.g. cancer patients with no other ongoing diseases). When a study is assessing effectiveness, it is determining whether a treatment will influence the disease. In an effectiveness study it is essential that patients are treated as they would be when the treatment is prescribed in actual practice. That would mean that there should be no aspects of the study designed to increase patient compliance above those that would occur in routine clinical practice. The outcomes in effectiveness studies are also more generally applicable than in most efficacy studies (for example does the patient feel better, come to the hospital less or live longer in effectiveness studies as opposed to better test scores or lower cell counts in efficacy studies). There is usually less rigid control of the type of patient to be included in effectiveness studies than in efficacy studies, as the researchers are interested in whether the drug will have a broad effect in the population of patients with the disease.

    • Joana Carvalho says:

      Hi David,
      Many thanks for your in-depth reply. It is always important to keep in mind that while the whole process behind clinical trials may be long and become frustrating to some degree, it follows specific rules that try to ensure patients’ safety.

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