Clinical Catch-Up: April 6-10
As the COVID-19 pandemic continues, companies are speeding clinical trials for new drugs and repurposed drugs against SARS-CoV-2, the virus that causes the disease. There are also non-COVID-19-related clinical trials continued, although companies are also reporting, in some cases, that trials have been delayed or enrollment has been suspended. Here’s a look.
COVID-19-Related Clinical Trials
Care Access Research launched the COVID-19 Clinical Trials Alliance. The plan is to connect sites, sponsors and CROs to speed COVID-19 trials. It views the next problem as quickly finding enough sites that can run efficient, high-quality COVID-19 trials. It will match research-enabled sites with study sponsors.
Izana Bioscience initiated a two-center compassionate use trial of namilumab (IZN-101) for patients with rapidly worsening COVID-19 in cooperation with the Humanitas Research Hospital and Humanitas University. It will take place in Bergamo and Milan, Italy. Namilumab is the company’s Phase III-ready monoclonal antibody against granulocyte-macrophage colony stimulating factor (GM-CSF) in development for rheumatoid arthritis and ankylosing spondylitis.
RedHill Biopharma’s opaganib has been granted compassionate use in Italy for COVID-19. It is being studied in a clinical trial in more than 130 healthy volunteers and oncology patients. The drug has been in a Phase I trial for advanced solid tumors and is in a Phase I/IIa trial in advanced cholangiocarcinoma (bile duct cancer) and in a Phase II trial in prostate cancer, individually and in combination with hydroxychloroquine.
CytoDyn announced that the first two COVID-19 patients have been treated with leronlimab under its Phase II clinical trial. It expects enrollment to accelerate this week. The drug has also been administered to 15 severely ill COVID-19 patients at four hospitals under emergency investigational new drug (EIND) approval. The company is also collaborating with the UK’s Department of Health to provide emergency access to leronlimab. They are working to set up clinical trial sites in the UK. The FDA recently cleared CytoDyn to launch a Phase IIb/III trial of the drug in severe and critically ill COVID-19 patients.
Alexion Pharmaceuticals is to launch a Phase II trial of Soliris in COVID-19, after a 10-patient proof-of-concept trial, which began 10 days ago. Soliris is approved for paroxysmal nocturnal hemoglobinuria, hemolytic uremic syndrome and myasthenia gravis. The drug impacts the complement system, part of the immune system.
Inovio Pharmaceuticals dosed its first patients in its Phase I trial of INO-4800, its DNA vaccine candidate to prevent COVID-19 infection. It will enroll up to 40 healthy adults in Philadelphia and Kansas City. Each patient will receive two doses of INO-4800 four weeks apart, with initial immune responses and safety data expected by late summer.
EpiVax Oncology and GAIA Vaccine Foundation (GVF) partnered to crowd-source funds for a project to accelerate a COVID-19 vaccine candidate (EPV-CoV19) into clinical trials in six months. They have also pledged to make a free license available to developing countries who qualify, in the context of the partnership. EPV-COV19 is a peptide-based, epitope-driven vaccine that can be quickly and safely manufactured in most countries.
Bellerophon Therapeutics submitted an INDA to study INOpulse Inhaled Nitric Oxide Therapy for treating COVID-19. The proposal is for a study, PULSE-CVD19-001, which would evaluate the efficacy and safety of INOpulse in COVID-19 patients who require supplemental oxygen.
Novavax reported it plans to begin Phase I clinical trials in mid-May for its COVID-19 vaccine candidate. In animal studies, the vaccine produced high levels of neutralizing antibodies against SARS-CoV-2. It will enroll 130 healthy adults, with data expected in July.
AstraZeneca is working with the Chinese Academy of Sciences and Vanderbilt University Medical Center to evaluate possible drug candidates for the disease. The two institutions provided the company with genetic sequences for antibodies against SARS-CoV-2 for further research. In addition, previous work with the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and the University of Maryland School of Medicine will conduct preclinical safety and efficacy tests of promising antibodies AstraZeneca already discovered. USAMRIID and U of M will utilize their biosafety level 3 (BSL3) laboratories.
Intermountain Healthcare and University of Utah Health launched two COVID-19 clinical trials to test the effectiveness and safety of hydroxychloroquine and azithromycin. As everyone probably knows by now, hydroxychloroquine is a treatment for malaria, as well as lupus and rheumatoid arthritis. Azithromycin (Z-Pak) is an antibiotic.
Gilead Sciences made changes to its remdesivir trials. According to clinicaltrials.gov, the remdesivir trial page was updated, changing the size of a study in severe patients from 400 to 2,400, and the moderate patient trial from 600 to 1,600.
Biohaven Pharma submitted Pre-IND/IND material to the FDA to initiate a Phase II trial of vazegepant for COVID-19 infection associated pulmonary complications. The drug is an intranasal, high-affinity calcitonin gene-related peptide (CGRP) receptor antagonist. The drug is currently advancing to Phase III for acute migraine.
Pfizer and BioNTech updated their development program, with plans to launch clinical trials in the U.S. and Europe across multiple sites by the end of April for their mRNA vaccine to COVID-19. Pfizer has also chosen a lead antiviral to test against the disease. In addition to this compound, the company is planning to begin testing its rheumatoid arthritis drug Xeljanz in COVID-19 patients in Italy, as well as research on some of its antibiotics.
CalciMedica received the go-ahead from the FDA to investigate the use of CM4620-IE in patients with severe COVID-19 pneumonia at risk for ARDS. The drug is a potent and selective small molecule CRAC channel inhibitor that prevents CRAC channel overactivation, which can cause pulmonary endothelial damage and cytokine storm in COVID-19.
Arcturus Therapeutics plans to launch a human clinical trial this summer for its COVID-19 vaccine, LUNAR-COV19. Under the guidance of the Singapore Health Sciences Authority, it plans to enroll up to 76 healthy adult volunteers.
CytoDyn reported immunological metrics from blood samples of seven severely ill COVID-19 patients after seven days of treatment with leronlimab. The results demonstrate dramatic immune restoration, especially in the CD8 T-lymphocyte population. It also reported a patient with severe COVID-19 in Southern California exhibited clinical improvement after leronlimab treatment.
Mesoblast Limited announced its allogeneic mesenchymal stem cell (MSC) product candidate remestemcel-L will be evaluated in a placebo-controlled trial in 240 patients with ARDS caused by COVID-19. The Phase II/III trial will be conducted in a partnership in collaboration with the Cardiothoracic Surgical Trials Network (CTSN).
Laurent Pharmaceuticals, a spin-off from McGill University, plans to test its lead compound LAU-7b in COVID-19 patients as part of a Phase II trial. The drug is a novel, once-a-day oral form of fenretinide, being developed to control inflammation in the lungs. A recent drug-library screening by researchers from the Institut Pasteur Korea suggested the drug also had anti-viral therapeutic properties against COVID-19.
FUJIFILM Holdings will begin a Phase II trial of its anti-flu drug Avigan for COVID-19 in the U.S. It will enroll about 50 COVID-19 patients. The drug inhibits RNA polymerase, which, like with the influenza virus, is needed by the novel coronavirus to replicate.
CanSino Biologics and collaborators at the Academy of Military Medical Sciences’ Institute of Biotechnology expect to soon move their adenovirus type-5 vector-based recombinant COVID-19 vaccine, Ad5-nCoV, into a Phase II clinical trial in China. Ad5-nCoV is a genetically engineered vaccine that uses an adeno-associated virus as a vector to express the S (spike) protein on SARS-CoV-2. The company indicated preliminary safety data from the Phase I trial was the basis of the progress.
Non-COVID-19-Related Clinical Trials
Immunomedics announced it has halted its Phase III confirmatory ASCENT clinical trial of sacituzumab govitecan in patients with metastatic triple-negative breast cancer (mTNBC). An independent Data Safety Monitoring Committee (DSMC) recommended they stop the trial because of “compelling evidence of efficacy.” The ASCENT Phase III trial is a confirmatory study to validate the safety and efficacy data seen in the Phase II trial of heavily pretreated mTNBC patients. The primary endpoint is progression-free survival (PFS) and secondary endpoints include overall survival (OS) and objective response rate (ORR).
Incyte announced it had presented the first Phase III data for ruxolitinib cream in atopic dermatitis. The research was presented at the Revolutionizing Atopic Dermatitis Virtual Symposium. The Phase III TRuE-AD program, including the TRuE-AD1 and TRuE-AD2 trials, are studying ruxolitinib cream 0.75% and 1.5% twice daily for patients with mild-to-moderate atopic dermatitis. The primary endpoint for the two trials was the proportion of patients hitting Investigator’s Global Assessment (KGA) Treatment Success (IGA-TS), defined as an IGA score of 0 (clear) or 1 (almost clear) with at least a two-point improvement form baseline, at Week 8. Both studies met the primary endpoint.
Menlo Therapeutics released topline results from two Phase III trials of once daily oral serlopitant for pruritus (itching) associated with prurigo nodularis (PN). Neither trial met their primary endpoint. PN is a skin disease that results in hard, itchy nodules forming on the skin. The itching can be intense, with some patients scratching until they bleed or cause themselves pain. The scratching can cause more of the nodules to form.
Serlopitant is a small molecule, highly selective NK1-R antagonist. NK1-R is one of two receptors (the other is Substance P or SP), that are critical mediators of the urge to scratch. NK1-R stands for neurokinin-1 receptor, which is a naturally occurring peptide in the tachykinin neuropeptide family. Tachykinins have numerous functions in the nervous and immune systems.
Catalyst Biosciences received guidance from the FDA and EMA on its pivotal Phase III trial design for marzeptacog alfa (activated)—MarzAA. It will evaluate the efficacy of subcutaneous MarzAA to treat episodic bleeding in hemophilia A or B with inhibitors. The Phase III CRIMSON-1 trial will enroll patients who experience episodic bleeding.
STRATA Skin Sciences published data from its clinical trial of XTRAC 308nm excimer laser in treating plaque psoriasis. In the study, 92% of patients responded to treatment and achieved a reduction in mPASI score of 75% or more.
Recce Pharmaceuticals formalized a Phase I trial agreement to run a first-in-human trial of its lead compound RECCE 327 in healthy subjects. It will be run at a specialized clinical trial facility in Sydney, Australia, independent of the hospital system. RECCE 327 is a broad-spectrum synthetic antibiotic formulated using synthetic polymer technology to treat blood infections and sepsis derived from E. coli and S. aureus bacteria.
Rexahn Pharmaceuticals terminated its clinical trial collaboration and supply agreement with Merck after it decided to discontinue development of RX-5902 for metastatic triple-negative breast cancer with Merck’s checkpoint inhibitor Keytruda. RX-5902 is a small molecule phosphorylated p68 inhibitor.
Cyclerion Therapeutics closed enrollment of its STRONG-SCD trial of olinciguat, a once-daily oral sGC stimulator that primarily targets the vasculature and highly perfused organs like lungs and kidneys for sickle cell disease. It has a total of 70 randomized participants. They expect topline data in the third quarter. Its Phase I trial of IW-6463, an oral, once-daily CNS-penetrant sGC stimulator for serious neurodegenerative diseases, also closed its trial with 24 elderly patients. The company is expecting topline data in mid-2020.
Clinical Trials Affected by COVID-19
Medidata, now owned by Dassault Systemes, issued a report on how clinical trials are being hammered globally by the COVID-19 pandemic. They noted that from 4,599 clinical studies and 182,321 study sites, the year-on-year difference between March 2019 and March 2020 across all reported countries and targeted disease areas showed enrollment had dropped 65% on average. The hardest hit was the UK, down 80.1%, and the U.S. down 66.7%. Endocrine disorders were the hardest hit, down 80%, with cardiovascular, central nervous system and dermatology down around mid- to high-60%.
Quantum Genomics indicated that its QGC001/1QG4 trial in end-stage renal failure was ongoing and all patients had been enrolled, with half of the healthy volunteers already completing the trial and all renal failure patients enrolled and treated. Enrollment for the remaining healthy volunteers has been temporarily halted. For patients in the QGC001/2QG4 (QUORUM) trial, some of the patients have already completed follow-up visits. Patients currently enrolled are having follow-up visits reorganized and, when possible, conducted remotely. The FRESH trial in resistant hypertension largely continues unchanged, with patient enrollment beginning as soon as possible.
Silk Medical Aesthetics, in partnership with Evolved by Nature, has been approved for a U.S. clinical trial of its all-natural, silk-based dermal filler. The trial will study an injectable form of Evolved By Nature’s patented Activated Silk technology in the nasolabial fold of the face for volume correction. However, although it is preparing for the trial, it can’t begin enrolling patients until after the pandemic recedes.
Otonomy reported that the primary endpoint for its OTIVIDEX Phase III trial and key exploratory endpoints in its OTO-313 Phase II trial are self-reported by the patient from home, so things are just fine despite the pandemic. However, new patient enrollment has been affected so they are suspending guidance for the timing of trial results. OTIVIDEX is evaluating dexamethasone in Meniere’s disease. OTO-313 is evaluating gacyclidine in tinnitus.