NIH to Launch Massive ACTIV-6 Phase 3 Clinical Study Investigating Repurposed Drugs & Ivermectin May be on the List

COVID-19, NIH, NCATS, ACTIV, ACTIV-6, Repurposed Drugs, Ivermectin

TrialSite is pleased to report that Francis S. Collins, MD, PhD, and the team at the National Institutes of Health (NIH) will fund a large, randomized, placebo‑controlled Phase 3 clinical trial to test several existing prescription and over-the-counter medications for people to self-administer to treat symptoms of COVID-19. Part of the Accelerating COVID‑19 Therapeutic Interventions and Vaccines (ACTIV) public–private partnership, the ACTIV-6 trial aims to provide evidence-based treatment options for the majority of adult patients with COVID-19 who have mild-to-moderate symptoms and are not sick enough to be hospitalized. NIH will provide an initial investment of $155 million in funding for the trial. TrialSite picked up inside rumblings that ivermectin will be one of the economical drugs under investigation. While this study is late in the pandemic, nonetheless TrialSite celebrates Collins and team’s movement in this most important of areas.

The Director: We Need to do more for Early Care!

Honesty is a good policy, and that was definitely part of the message Director Collins recently issued in the apex research agency’s recent press release. Dr. Collins went on the record, “While we’re doing a good job with treating hospitalized patients with severe disease, we don’t currently have an approved medication that can be self-administered to ease symptoms of people suffering from mild disease at home, and reduce the chance of their needing hospitalization,” said NIH Director Francis S. Collins, M.D., Ph.D. “ACTIV-6 will evaluate whether certain drugs showing promise in small trials can pass the rigor of a larger trial.”

Where have you been?

Some would argue this would have been great news had this been summer 2020. The whole point of repurposing was to get going on a number of major repurposeable drug candidates so society could potentially benefit sooner. A number of early studies TrialSite reported on evidenced many dozens of candidates, from an effort at UCSF and the Sanford Burnham study to the Scripps and Calibr efffort. There we so many options not to mention the striking news from Monah University about a drug that absolutely destroyed SARS-CoV-2 in a cell culture in 48 hours—Ivermectin.   

But rather than pursuing any of these promising candidates over the past year this apex research body helped allocate billions of dollards to just a handful of vaccine and novel therapeutics while specifically excluding repurpsoed drugs except for a couple of instances in the ACTIV program.  From this perspective, Collins and leadership have completely failed in their responsibilities and in their marshalling of taxpayer dollars for the public’s health. As TrialSite has posited all along, it should have never been an “either or” false dilemma. All avenues should have been investigated and the repurposing was the fastsest and most effective option from the start.

Drugs Under Study

Several drugs currently are recommended for the treatment of hospitalized patients with moderate to severe COVID-19, including the antiviral drug remdesivir, the anti-inflammatory baricitinib, and corticosteroids. Additionally, the U.S. Food and Drug Administration authorized emergency use of intravenous monoclonal antibodies in non-hospitalized patients with mild to moderate COVID-19 who are at high risk for severe disease. However, medications that can be self-administered at home to reduce COVID-19 symptoms are critically needed.

Not included on the list are drugs such as ivermectin, which TrialSite has picked up via chatter in its network that the drug used in many other countries now will be under investigation. TrialSite hasn’t verified this fact however.

The ACTIV-6 protocol will explore a pool of up to seven drugs approved by FDA for other conditions – an approach called drug repurposing – and test their safety and effectiveness in treating mild to moderate COVID-19. Because the drugs under consideration already have been tested in humans, repurposing could deliver COVID-19 treatment options sooner. Drugs will be administered orally or by inhaler and will be easy for participants to take at home. Participants will be assigned randomly to receive either a placebo or one of the treatments, which will be sent to them by mail.

ACTIV-6: A Major Study

Enrollment is expected to open in a few weeks to up to 13,500 participants who are at least 30 years old, have tested positive for SARS-CoV-2 infection and have experienced two or more mild-to-moderate symptoms of COVID-19 for no more than seven days. Researchers plan to assess changes in patients’ symptoms over a 14-day period, as well as hospitalizations and deaths over a 28-day period. They also will assess long-term COVID-19-related symptoms at 90 days after treatment begins. The list of drugs that will be added to the study arms is still being finalized. All the drugs will have established safety records and early indications from smaller or less controlled studies of effectiveness against COVID-19.

The trial will focus on enrollment of people within minority, rural and other communities that are significantly affected by COVID-19 but lack access to major academic medical centers, where large clinical trials usually take place.

Overseen by NCATS & Partnered with PCORI

With funding provided by the American Rescue Plan Act, NIH’s National Center for Advancing Translational Sciences (NCATS) will oversee the trial. The Duke Clinical Research Institute, Durham, North Carolina, an NCATS-funded Clinical and Translational Science Awards (CTSA) Program hub, will serve as the clinical coordinating center, and the Vanderbilt Institute for Clinical and Translational Research CTSA Program hub at Vanderbilt University Medical Center, Nashville, Tennessee, will serve as the trial’s data coordinating center.

To expedite enrollment in ACTIV-6, NCATS and its Duke-Vanderbilt Trial Innovation Center will partner with the Patient-Centered Outcomes Research Institute (PCORI), an independent nonprofit research funding organization. PCORnet, the National Patient-Centered Clinical Research Network, which is funded by PCORI, will support the ACTIV-6 governance and operations. In addition, PCORnet sites will enroll participants from a broad range of communities.

“Getting approval for a new drug to come to market usually takes years,” said Joni Rutter, Ph.D., NCATS acting director. “By leveraging drug repurposing and existing national clinical trial networks, ACTIV-6 aims to speed the delivery of definitive answers about available drugs that could help people manage COVID-19 symptoms at home.”

About the National Center for Advancing Translational Sciences (NCATS) 

NCATS conducts and supports research on the science and operation of translation — the process by which interventions to improve health are developed and implemented — to allow more treatments to get to more patients more quickly. For more information about how NCATS helps shorten the journey from scientific observation to clinical intervention, visit their website.

About the National Institutes of Health (NIH)

NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Call to ActionTrialSite will monitor this imminent study for updates.

Responses

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  1. This is why people seek their own remedies. Delay after delay, with no immediate response from most of the nation’s practicing medical doctors to administer medication on their own given knowledge and authorization for compassionate care. While waiting once again for pomp and ceremony attributed to formalizations and hearing “from the top”, Isaac medical physicians are letting the long haulers and the newly infected people down.

    Doctors can prescribe Ivermectin NOW, repurposed and off-label…the focus of treating people NOW is still being neglected and is subordinated to the focus of NIH clinical trials with competition from other agents of possible therapeutic value.

    Why wait?

  2. Should be “USAs” medical physicians” not “Isaac” medical physicians. I am sorry that my auto-correct jumps in there at the last moment. Please edit…(?) Thanks!

  3. Disparaging Collins for the alleged “slow roll” of NIH repurposed drug RCTs is unhelpful. Adherents to various repurposed therapies would better serve the public good by advocating for their chosen treatment. Because, if a treatment isn’t present, then the inevitable result will be for the adherents to claim that the government is engaged in a conspiracy with big pharma and that the entire ACTIV-6 study is a sham.
    Come to think of it, I won’t be at all surprised if someone responds to my comment that the study is already a sham before it begins, so there’s no point in trying to advocate for a particular therapy.
    To which I would respond, “If you want to win, then you have to fight — otherwise, you will lose.” Way of the world since time began.

      1. ACTIV
        https://directorsblog.nih.gov/2021/02/16/activ-update-making-major-strides-in-covid-19-therapeutic-development/
        My post was not, No,t a knee-jerk response from me, I was agreeing with the writer that this news would be more “Wow!” had it been after the Monash study last year…I’ll use a patient tone of voice as we who are waiting for officialdom ask, “What would be helpful, then?”

        The writer of this article quoted an official:
        “Getting approval for a new drug to come to market usually takes years,” said Joni Rutter, Ph.D., NCATS acting director. “By leveraging drug repurposing and existing national clinical trial networks, ACTIV-6 aims to speed the delivery of definitive answers about available drugs that could help people manage COVID-19 symptoms at home.”

        Did we catch that?
        “…at home…”
        Are we going to be allowed to use monoclonal antibodies, equine antibody sera-based globulin “at home”? Ivermectin…at home…without prescriptions?
        Our question: What about Ivermectin treated as Aspirin and as allergy medications are treated?
        How about a cross-discipline and intra-medicine (veterinarian/human) study to verify or refute the efficacy and safety of what people have already used… veterinarian or oeople version – so that “fact-checked” stories about alternative therapeutic treatments for COVID-19 get the axe when they are found to be exaggerated, misconstrued or suppressive? We are not all afraid of letting go of the paranoia of people administering medications to themselves. How many people die or are maimed for life, from asprin or vitamin D3? Will the NIH approve of “at home” use of vitamin D, quercetin, alpha lipoic acid, melatonin, zinc and natural antibiotic/antiviral agents?
        Why the emphasis on synthetic medicine studies?

      2. Lilly and Regeneron antibody cocktails were proven effective. That the drugs require infusion prior to hospitalization does not diminish their effectiveness, tho it certain makes delivery more difficult.
        Regeneron is currently working on a version of its therapy using subcutaneous injection. Thus far, the new delivery mechanism appears to be as effective against SARS-CoV-2 as the current crop of vaccines.
        See, https://newsroom.regeneron.com/news-releases/news-release-details/phase-3-prevention-trial-showed-81-reduced-risk-symptomatic-sars

  4. I wonder if the announcement of the ACTIV-6 trial will essentially be NIH’s way of endorsing several early treatment options. They didn’t even put much thought into the trial details but they stated:

    “All the drugs will have established safety records and early indications from smaller or less controlled studies of effectiveness against COVID-19.”

    ie – these are the medications that the NIH views as having low risk but a reasonable chance of effectiveness.

      1. ACTIV

        My post was not, Not, a knee-jerk response from me, In saying I’ll use a patient tone…

        “ACTIV was founded last April to accelerate drug research that typically requires more than a decade of clinical ups and downs to develop a safe, effective therapy. And ACTIV has indeed moved at unprecedented speed since its launch. Cutting through the usual red tape and working with an intense sense of purpose, the partnership took a mere matter of weeks to set up its first […]”

        I worked for the federal government for twenty years, doing water quality studies. One study I was involved in needed to have the team hydrologists’ results made available to the public in a publication stating the water quality of the river system that I had sampling stations located on. From a tiny bottle of sample of stream water, at a particular moment in time during the act of sampling, at a particular volume, stage and velocity and at a particular season, they were supposed to publish the presence of samples constituents (i.e., iron, nitrogen as NH4, suspended sediment) in terms such as “tons per year”. While a study can be done quickly, it takes many days of sampling at different seasons, different flows and at different levels of contaminant influx. I was the one who, as the sampler, determined the results. If my sampling was biased, the outcome would be biased. No one really knows effective my sampling was once the results were published and the people that asked “How’s the water?” were anxious to read the numbers. Then they came to conclusions, officially, since the publication came from the government.

        Clinical trials are similar.

        Real-world experience might be more like a fly-fisher person catching a healthy fat trout on the river (exhibits good enough dissolved O2 for the fish, who is particular about that) but the successful fisherperson saying, ” the river seemed kinda muddy today, I was lucky that the fish saw the fly.”

        We don’t have time for successful clinical trials while people are getting infections from SARS-CoV-2 and its multiple strains…
        Catch a fish and state your real-world experience. Then report it to the authorities.

  5. There is no time or need for more trials. Ivermectin has been proven safe millions of times over. The acceptable dosage has been established. 12 mg once a week for prevention and 12 mg day 1, day 3, day 5 and so on until symptoms go away. FLCCC has gathered the information and distributes it freely trying to save lives. Ivermectin should be sold over the counter and everyone on the planet should be taking 12 mg once a week. It wont hurt anyone and has been proven to help. Why must it be proven to help again if it can’t hurt. Are the experts afraid someone may take it and not get better? People have been not getting better for over a year now.

    1. That is not the dosage FLCCC suggests. They suggest a dosage based on body weight.

      And what they have suggested in the past will be updated within a week, based on the growing body of evidence.

  6. One aspect of the traditional double blind randomized control trials is that a test arm is often represented by a administrating a single drug and observing efficacy in comparison to placebo.

    Recent science in outpatient treatment
    (paper by McCullough et al) See PDF download: https://t.co/5jKnN7N7RY?amp=1
    pioneer “Multidrug Sequenced Treatment” in outpatient treatment of covid-19, meaning several drugs have empirically in practical treatment of covid-19 outpatients found to have effect when combined in a certain phase of the infection. It means that throughout the course of treating a patient from first symptom to optimally ending in recovery, a whole battery of different medications were combined as determined purposeful in the given situation. This experience / knowledge does sound heavyweight compared to having applied a single drug as the treatment in a RCT and comparing the result to the outcome for a patient that receive placebo ?
    So how will these approaches compare and be put to best use ?
    It seems the environments where outpatient doctors have practiced the multi sequenced approach they are able to source drugs under “off-label use” terms.