4 August 2020 - - The first patients has been enrolled in the I-SPY COVID Trial (Investigation of Serial Studies to Predict Your COVID Therapeutic Response with Biomarker Integration and Adaptive Learning) clinical trial, according to members of the COVID R and D Alliance AbbVie, Inc. (NYSE: ABBV), Amgen Inc. (NASDAQ: AMGN), and Takeda Pharmaceutical Co. Ltd. (NYSE: TAK).

The I-SPY COVID Trial will evaluate the efficacy of cenicriviroc, a chemokine (CCR2 and CCR5) dual-receptor antagonist, Otezla (apremilast), a PDE4 inhibitor, and Firazyr (icatibant injection), a bradykinin B2 receptor antagonist in severely ill, hospitalized COVID-19 patients who require high-flow oxygen.

The I-SPY COVID Trial utilizes Quantum Leap Healthcare Collaborative's adaptive platform trial design, which is intended to increase trial efficiency by minimizing the number of participants and time required to evaluate potential treatments.

The study is a collaboration between members of the COVID R and D Alliance, Quantum Leap, and the US Food and Drug Administration.

AbbVie, Amgen, and Takeda are members of the COVID R and D Alliance (COVID R and D), a group of more than 20 of the world's leading biopharmaceutical and life science companies working to speed the development of potential therapies, novel antibodies, and anti-viral therapies for COVID-19 and its related symptoms.

The therapies under investigation were selected based on their potential to impact the immune system response of COVID-19 patients who need respiratory support.

Approximately 10-15 % of patients afflicted by COVID-19 develop acute respiratory distress syndrome, and up to 60 % of those patients admitted to an ICU require ventilation for an average of two weeks. It is estimated that half of those patients will not survive.

Based on the respective mechanisms of action, Otezla may suppress inflammation resulting from an immune response, Firazyr may ameliorate bradykinin-driven pulmonary edema, and cenicriviroc acts by blocking monocytes trafficking to tissues, features that may help to reduce or mitigate the severity of ARDS response in severely ill COVID-19 patients.

I-SPY COVID is one of several platform studies being pursued by members of COVID R and D to test promising therapeutic candidates faster than any single company could do operating alone.

Members are investigating marketed and late-stage therapies indicated for other disease states, which, based on their mechanisms of action may have a potential treatment effect in COVID-19 patients.

The group is employing adaptive platform trial methodologies that enable the ability to test multiple therapies simultaneously and modify protocols in real-time based on outcomes observed.

In addition to designing and sponsoring several platform trials, the COVID R and D Alliance is:

Evaluating more than 1,900 preclinical candidates against active controls to uncover which hold the greatest promise for COVID-19.

Reviewing promising early-stage candidates that may show potential efficacy against COVID-19, and connecting them with potential funders from venture capital or pharmaceutical developers to enable rapid advancement.

Working with TransCelerate's DataCelerate platform to enable real-time data sharing and real-world evidence to inform ongoing and future studies in COVID-19, so research communities benefit from learnings and avoid duplication.

Operating as an interlocutor with governments, regulators, and non-governmental organizations to share insights and engage in other platform trials.

The I-SPY COVID Trial (Investigation of Serial Studies to Predict Your COVID Therapeutic Response with Biomarker Integration and Adaptive Learning) is an adaptive platform trial designed to increase trial efficiency by minimizing the number of participants and time required to evaluate experimental and/or repurposed drugs.

The focus of the trial is to improve outcomes for severely-ill COVID-19 patients--those who require at least 6L of high-flow oxygen either by mask or nasal cannula, known as level 5 on the World Health Organization COVID scale, an 8 point ordinal scale of clinical severity status.

The primary endpoint of I-SPY COVID is time to achieve level 4 (or less) for at least 48 hours on the WHO COVID scale. Key secondary endpoints include duration of time on ventilator and mortality.

The I-SPY COVID Trial is sponsored and managed by Quantum Leap Healthcare Collaborative.

Organized in March 2020, the COVID R and D Alliance is operating unconstrained by past models of development and is accelerating study candidates without regard to company affiliation.

Members are sharing clinical trial data and real-world evidence, as well as crowd-sourcing early stage candidates to identify mechanisms and treatments that may be effective against COVID-19.

Initial efforts by the group focus on advancing well understood therapies and late-stage investigational medicines for severely ill patients who need options.

Future activities will expand to testing re-purposed molecules, early stage candidates, and therapeutic drug combinations.

CVC is an oral, once-daily, potent immunomodulator that blocks two chemokine receptors, CCR2 and CCR5, which are intricately involved in the inflammatory and fibrogenic pathways in nonalcoholic steatohepatitis known to cause liver damage including cirrhosis, liver cancer, or liver failure.

These pathways have also been shown to be closely involved with the respiratory sequelae of COVID-19 and of related viral infections.

Because of CVC's unique mechanisms of action, the drug has been viewed as having a potential role in the treatment of COVID-19 patients, in addition to its potential in the management liver fibrosis due to NASH, including as a part of combination-treatment strategies.

CVC has been studied in both NASH patients and in HIV+ patients, and is in Phase 3 development for NASH. CVC has been granted Fast Track status in adults with liver fibrosis due to NASH, the population at highest risk of progression to cirrhosis.

OTEZLA (apremilast) is an oral small-molecule inhibitor of phosphodiesterase 4 specific for cyclic adenosine monophosphate.

PDE4 inhibition results in increased intracellular cAMP levels, which is thought to indirectly modulate the production of inflammatory mediators. The specific mechanism(s) by which Otezla exerts its therapeutic action in patients is not well defined.

Otezla is currently approved for use in more than 45 countries as an oral treatment for inflammatory diseases including psoriasis, psoriatic arthritis and Behçet's disease. 

By inhibiting PDE4, Otezla is thought to modulate the production of inflammatory cytokines and other mediators, which may prove helpful in inhibiting the inflammatory response associated with the signs, symptoms and pulmonary involvements observed in some COVID-19 patients.

Amgen plans to collaborate with platform trials to investigate Otezla's ability to prevent clinical deterioration in patients with COVID-19.