clinical trials Archives - Sanford Burnham Prebys

Tag: clinical trials

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New COVID-19 drug passes phase 2 clinical trial

AuthorMiles Martin
Date

January 20, 2022

Illustration of red coronavirus particles against a dark blue background

The new treatment, developed by Avalo Therapeutics with Sanford Burnham Prebys researchers, can mitigate lung damage and improve survival in COVID patients.

In a phase 2 clinical trial conducted by Avalo and supported by Sanford Burnham Prebys, a significantly higher proportion of hospitalized patients with COVID-19 remained alive and free of respiratory failure for 28 days after receiving treatment with the new antibody, called CERC-002. Unlike other experimental COVID therapies, CERC-002 does not target the virus itself, instead targeting the immune response associated with the virus to stop the disease from progressing before it becomes fatal.

“At the beginning of the pandemic we thought vaccines were going to be all we really needed. But with variants like omicron, we’re going to have more people that progress to serious illness even with the vaccine,” says study coauthor Carl F. Ware, PhD, director of the Infectious and Inflammatory Diseases Center at Sanford Burnham Prebys. “We need treatments to stop the progression to severe disease and death.”

The findings were published December 6 in the Journal of Clinical Investigation.

COVID-19: a continuing crisis
In the United States, over 840,000 people have died from COVID-19. A large proportion of these deaths have been among the elderly or those who are immunocompromised due to a preexisting condition. And while three quarters of the population has received at least one dose of the COVID-19 vaccine, many remain unvaccinated.

“A lot of us feel safer now that we’ve gotten our shots,” Ware says, “but the threat of the pandemic has not gone away, even for vaccinated people.”

Most people with COVID-19 experience few to no symptoms. However, elderly individuals, people with a concurrent health condition or those who are immunocompromised are susceptible to a condition called cytokine storm, in which their own immune molecules called cytokines flood the body in higher concentrations than usual.

Rather than helping fight the virus, these extra immune molecules wreak havoc, causing patients to develop the deadly respiratory failure characteristic of severe COVID disease.

“The COVID virus gets the immune system amped up by producing these molecules, which is normally how the immune system fights diseases,” says Ware. “But when there are too many cytokines and they’re not doing their job, it can lead to severe damage.” 

Neutralizing the cytokine storm
The new treatment, CERC-002, is a cytokine neutralizer—an immune molecule that recognizes and deactivates a cytokine known as LIGHT, which is elevated in patients with COVID-19. Cytokine neutralization drugs are currently being tested in the clinic, but they are mainly effective in severely ill patients who are already on a ventilator or other organ support.

“There is a critical need for drugs to stop milder cases from progressing to severe,” says Ware. “This treatment targets the cytokine immune response early enough to stop it in its tracks, which no other treatment does right now.”

83 COVID patients were enrolled in the study, half receiving the treatment, and half receiving a placebo. All patients were hospitalized with mild-to-moderate respiratory distress and were also receiving standard-of-care therapy during the trial.

They found that 83.9% of patients who received a dose of CERC-002 on top of standard of care remained alive and free from respiratory distress for 28 days. For patients receiving placebo, the number was only 64.5%.

Looking ahead
As a phase 2 clinical trial, the purpose of this study was to test whether the compound has therapeutic potential in a small number of patients. Now that the drug has proven successful at a small scale, it can be tested on a larger number of patients to ensure its benefits are consistent across the population.

Additionally, because CEC-002 targets the immune response in COVID cases rather than the virus itself, the compound may have applications that extend beyond COVID.

“Cytokine storm is not unique to COVID. It occurs in other infections—even in autoimmune diseases with no active infection, so this treatment may have some utility in these other diseases as well.” 
While there is more work to be done before CERC-002 becomes widely available, it does offer a glimmer of hope during a pandemic that seems never-ending.

“We have made a lot of progress in controlling the pandemic with vaccines and other new therapies, but it’s not over yet,” says Ware. “Treatments like this may bring physicians an option to protect infected people from severe illness.

Institute News

Sanford Burnham Prebys drug enters Phase 1 study for the treatment of tobacco use disorder

AuthorSusan Gammon
Date

August 26, 2021

Senior doctor breaking a cigarette

A drug discovered in the lab of Nicholas Cosford, PhD, professor and deputy director of the NCI-designated Cancer Center at Sanford Burnham Prebys, has entered a Phase 1 clinical study.

The compound, SBP-9330, targets a neuronal signaling pathway underlying addictive behaviors and would be a first-in-class oral therapeutic to help people quit smoking. 

The study is being funded by the National Institute on Drug Abuse (NIDA) at the National Institutes of Health (NIH) through a grant awarded to Sanford Burnham Prebys, the Department of Psychiatry, University of California San Diego, School of Medicine, and Camino Pharma, LLC, who will oversee activities related to the Phase 1 study.  

“Smoking continues to be the leading cause of preventable death in the US. Nearly 70% of adult smokers try to quit smoking, but only succeed less than 30% of the time, and often relapse after quitting,” says Cosford, who is also co-founder of Camino Pharma. “It has been 15 years since the U.S. Food and Drug Administration (FDA) last approved a therapeutic for this indication. We hope that SBP-9330 ultimately becomes a viable therapeutic option for smokers to quit for good.”

As a novel selective positive allosteric modulator of the metabotropic glutamate receptor 2 (mGlu2), SBP-9330 is designed to reduce levels of glutamate, a neurotransmitter linked to addiction and relapse behavior. Preclinical studies of SBP-9330, supported by a previous NIDA grant awarded to the same three institutions, demonstrated that the drug candidate reduces nicotine self-administration in animal models and is safe and well tolerated in preclinical safety and toxicology studies.

“We are excited to initiate the first-in-human study of SBP-9330 and are grateful for the investment the NIDA has made in the treatment of tobacco use disorder,” says Gonul Velicelebi, PhD, CEO and co-founder of Camino Pharma. “In the future, we also hope to broaden the indication of SBP-9330 to other types of addiction, such as cocaine, opioid, or methamphetamine use disorders. This is supported by preclinical data in other models of substance abuse as well as the mechanism of action of SBP-9330.”

The randomized, placebo-controlled, double-blind, single-ascending and multiple-ascending dose study is being conducted at a single site in the United States under an Investigational New Drug (IND) application recently allowed by the FDA and will enroll up to 80 healthy volunteers through multiple cohorts. The goal of the study is to determine the safety, tolerability and pharmacokinetic profile of SBP-9330 in humans and to determine a safe dose range for further clinical development SBP-9330 for the treatment of people with tobacco use disorder. 

“We are excited about collaborating in the development of SBP-9330 to treat tobacco use disorder. Each year in the United States, roughly half a million people die from tobacco-related diseases. It is critical to have more therapeutic options if we want to reduce the number of deaths and illnesses related to smoking,” says Robert Anthenelli, MD, UC San Diego professor of psychiatry and one of the co-principal investigators on the NIDA project.

Dr. Cosford has an equity interest in Camino Pharma, LLC. Dr. Cosford’s relationship with Camino Pharma, LLC has been reviewed and approved by Sanford Burnham Prebys in accordance with its conflict-of-interest policies.

Institute News

COVID-19: Renowned scientist enters clinical trial

AuthorSusan Gammon
Date

September 17, 2020

Carl Ware getting vaccinated

Meet Carl Ware, PhD, director of the Infectious and Inflammatory Disease Center at Sanford Burnham Prebys. After a career of studying how viruses wreak havoc on our health, he now becomes a “subject” in a COVID-19 clinical trial. 

What inspired you to enroll in a COVID-19 clinical trial?
I’m an immunologist working on coronaviruses. I understand the science of vaccines and the protection provided against infections. I also know how important clinical trials are to developing safe and effective vaccines. I trust the science, so I stepped up to volunteer for the vaccine trial. Who better than an immunologist to be part of this grand experiment? 

Are you nervous? 
Excited is more accurate.

Do you know which vaccine you’re getting?
Yes, the RNA-based vaccine by Moderna. It’s not a live virus! The vaccine uses a small part of the virus that allows the virus to attach to lung cells. To cause disease, a virus must replicate inside a cell. The infected cell dies, releasing large numbers of new viruses. The progeny virus infects more lung cells, producing more virus that reaches levels that are easily spread to other people. The vaccine stimulates the immune system to block the virus from entering and replicating in the lung cells, stopping the infection and spread to other persons.

How many people are in the trial?
About 30,000 people will participate. The volunteers are placed into two groups receiving either the vaccine or a placebo. The study is “blinded,” so I don’t know which group I’m in, but I’m hoping it’s not the placebo group. The preliminary tests of this new vaccine indicate it is safe and stimulates the immune system. However, proof of safety and effectiveness requires a large number of volunteers. More volunteers are needed to complete the goal of 30,000. 

How will you be evaluated during the trial? 
Following the first injection, I will report my symptoms every night for a week using a simple, very cool app on my cell phone. A month later, I will receive a booster and follow the same procedure with the phone app. I have two more visits to the site at six months and a year to determine if the vaccine stimulated long-lasting immunity.

How will it be determined if the vaccine works?
All sorts of tests will be used to measure the response of my immune system. No worries, volunteers in the trial will not be infected with the virus!

The trial is open to anyone who wants to participate, especially those persons most vulnerable, with serious diseases; front-line and essential workers; those over 65, Black and Latinx persons, and people with other health risks. There are several test centers around the San Diego area. More information on volunteering is at eStudySite.
 

Institute News

Immune therapy enters Phase 1 clinical trial

AuthorMonica May
Date

November 15, 2018

Lilly and SBP logos

Sanford Burnham Prebys Medical Discovery Institute (SBP) today announced that the first healthy subject has been dosed in a Phase 1 clinical trial evaluating LY3361237, a biologic that inhibits inflammation by activating an immune checkpoint receptor. LY3361237 arose from a research collaboration between Eli Lilly and Company (Lilly) and SBP formed in 2015 that seeks to discover and develop new immunological therapies. 

Diseases such as lupus, psoriasis and rheumatoid arthritis result from dysfunction of the immune system. Many of these conditions are characterized in part by immune checkpoint failure, resulting in the immune system attacking normal tissue. Previous studies have shown that activating checkpoint receptors can suppress inflammation and restore immune balance—indicating its therapeutic potential. More than 80 diseases are caused by the immune system attacking the body’s own organs, tissues and cells, according to the National Institutes of Health (NIH).  

“Today’s milestone is an important step forward for patients who suffer from autoimmune disease,” says Carl Ware, PhD, director of the Infectious and Inflammatory Diseases Center at SBP. “This advance also illustrates how the fundamental understanding of a biological process—in this case, the role of checkpoint receptors in immune function—can translate to the development of new medicines.”

“Immunological disorders—many of which disproportionately impact women—affect millions of people around the world and remain an area of great medical unmet need,” adds Ajay Nirula, MD, PhD, vice president of Immunology at Lilly. “Our collaboration with SBP is a powerful example of how uniting complementary areas of expertise—deep foundational scientific knowledge from SBP combined with expertise in protein engineering, immunobiology and clinical development from Lilly— can lead to a promising new candidate to treat autoimmune disorders.”

The study will evaluate the safety, tolerability and pharmacokinetics of LY3361237 in healthy subjects. Further information about the trial can be found on ClinicalTrials.gov using the Identifier NCT03695198.

Interested in keeping up with SBP’s latest discoveries, upcoming events and more? Subscribe to our monthly newsletter, Discoveries.

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SBP scientist honored by the American Society for Bone and Mineral Research

AuthorMonica May
Date

September 28, 2018

José Luis Millán, PhD

José Luis Millán, PhD, professor in the Human Genetics Program at Sanford Burnham Prebys Medical Discovery Institute (SBP), has received the 2018 American Society for Bone and Mineral Research (ASBMR) Lawrence G. Raisz Award for his outstanding achievements in pre-clinical and translational research. 

Millán has dedicated his career to understanding the mechanism of initiation of skeletal and dental mineralization. His pioneering research has led to the first-ever FDA-approved drug for a rare soft bone disease, hypophosphatasia (HPP); and a second drug candidate developed through a research collaboration with Daiichi Sankyo Company, Limited (Daiichi Sankyo) that entered a Phase 1, first-in-human clinical trial in 2017. 

ASBMR’s award is named in honor of Lawrence G. Raisz, MD, a prominent scientist, mentor, teacher and clinician in the field of bone and mineral metabolism. Raisz was a founding member of ASBMR and the first editor-in-chief of the Journal of Bone and Mineral Research. 

“Lawrence G. Raisz deeply influenced the skeletal mineralization field, so it is a true honor to receive an award in his memory,” says Millán. “In accepting this award, I want to thank the many individuals who enabled our achievements—from the National Institutes of Health (NIH), which has generously funded our research since the 1980s, to the collaborators and lab members who were instrumental in our scientific advances. I also want to thank SBP for providing state-of-the-art technologies that were invaluable to our research.”

Millán was presented the award onstage today at the ASBMR 2018 Annual Meeting in Montreal. 
 

Interested in keeping up with SBP’s latest discoveries, upcoming events and more? Subscribe to our monthly newsletter, Discoveries.

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Discovery from the lab of Carl Ware, PhD leads to clinical trial in pediatric Crohn’s disease

AuthorJessica Moore
Date

December 8, 2016

child with abdominal pain

Just about any of the 700,000-plus people in the U.S. who have Crohn’s disease, a chronic condition in which portions of the intestine are inflamed, can tell you that better treatments are urgently needed. Even with medication, most experience flare-ups that keep them away from work or school for days or weeks at a time with diarrhea and severe abdominal pain.

A soon-to-commence clinical trial could offer Crohn’s patients new hope. The trial will test a drug made possible by a discovery from the lab of Carl Ware, PhD, professor and director of the Infectious and Inflammatory Diseases Center at Sanford Burnham Prebys Medical Discovery Institute (SBP). Almost two decades ago, his team identified an immune-regulating protein called LIGHT, and went on to show that it promotes intestinal inflammation. The new drug is a protein that prevents LIGHT from binding its target receptor on T cells, the immune cells that drive inflammation in Crohn’s disease.

“We’re thrilled to see our research through to a clinical trial,” said Ware. “We’ve focused on patients with a rare mutation that causes especially severe, early-onset disease. If the drug proves beneficial to those patients, we expect to pursue a larger trial in patients with typical Crohn’s.”

The trial will test the LIGHT-blocking drug in children with Crohn’s disease who carry a mutation in the gene for a protein called DcR3, which normally limits the amount of LIGHT and two other related pro-inflammatory molecules. The genomics company Medgenics will conduct the clinical trial with physician-scientist Robert Baldassano, MD, at the Children’s Hospital of Philadelphia.

Ware’s lab will be involved in fundamental research aspects of the study, developing assays to measure levels of LIGHT in patient plasma. In parallel, his team will be studying how the drug affects the microbiome in animal models.

“We are also applying what we’ve learned about LIGHT and the receptors it interacts with to other autoimmune diseases,” said John Sedy, PhD, research assistant professor in Ware’s group. “We’re working towards treatments that modulate the immune system in different ways.” 

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Why share data from clinical trials? SBP’s CEO Perry Nisen weighs in

AuthorKristen Cusato
Date

September 26, 2016

conceptual image of clinical data

Sharing clinical trial data with researchers who weren’t involved in the original study maximizes the value of patients’ participation, allowing more research questions to be answered than those of the original study. However, figuring out what data should be shared and how to do it has proven to be difficult.

The most recent issue of the New England Journal of Medicine devoted three perspective articles and an editorial on the topic of data sharing. Perry Nisen, MD, PhD, CEO of Sanford Burnham Prebys Medical Discovery Institute (SBP) and his colleagues discuss efforts to share clinical trial data and the hurdles that investigators still face.

“One of the risks is that there will not be a single simple system where these data can be accessed and analyzed, and the benefits of meta-analyzing data from multiple studies will be limited by cost and complexities,” said Nisen.

GlaxoSmithKline was a first mover in making anonymized patient-level data available from clinical trials. In 2013, the Clinical Study Data Request was established. The site is now managed by the Wellcome Trust, an independent, non-sponsor safe harbor, and includes more than 3,000 trials from 13 industry sponsors.

 

Nisen answers key questions about the future of clinical data sharing:

Q: Why should research sponsors go to the expense of sharing data?

Clinical data sharing is the right thing to do for science and society. First, it increases transparency of clinical trial data. It maximizes the contribution of trial participants to new knowledge and understanding. This allows researchers to confirm or refute findings, and enables them to generate other hypotheses. Scientific research globally is moving toward more transparency in clinical trial reporting and this is an important step toward building trust.

 

Q: What are the challenges to a one-stop shop for sharing all clinical trials data?

Protecting patient privacy and confidentiality is a major concern. Also, ensuring the data are used for valid scientific investigation, preventing erroneous claims of benefit or risk, and controlling the cost associated with anonymizing data in formats investigators can utilize effectively.

Other challenges inherent in data sharing include patient consent, data standards, standards for re-use, conflicts of interest, and intellectual property.

 

The editorial, also co-authored by Frank Rockhold, PhD, professor of biostatistics and bioinformatics at the Duke Clinical Research Institute, and Andrew Freeman, BSc, head of medical policy at GlaxoSmithKline, is available online here.

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Can your heart prevent diabetes?

AuthorGuest Blogger
Date

November 19, 2015

Header image

This article was written by guest blogger Crystal Woodard, PhD

Can your heart prevent diabetes? Being overweight or obese is currently deemed the single best predictor of type 2 diabetes. With the prevalence of obesity on the rise, estimates suggest that one in three American adults could have type 2 diabetes by 2050. Weight loss is key to preventing this epidemic. At SBP, scientists are investigating how hormones released by the heart may help the body burn more calories to prevent obesity and type 2 diabetes.

What color is your fat? All fat is not created equal. Excess weight is held in energy-storing fat cells called white adipose tissue as well as energy-burning fat cells called brown adipose tissue. Increasing a person’s brown fat could improve the risks associated with obesity.

Two compounds released by the heart in response to high blood pressure—human atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)—have been found to play a direct role in “browning” white adipose tissue. By browning, white fat starts to burn more calories, mimicking what occurs in brown fat. Sheila Collins, PhD, professor in the Integrative Metabolism Program and her research team, are investigating how these natriuretic peptides activate fat browning with the goal of tapping into the process to help promote weight loss and prevent diabetes.

In collaboration with Dr. Richard Pratley at the Florida Hospital – SBP Translational Research Institute for Metabolism and Diabetes, the teams are conducting clinical trials with obese and lean volunteers to test whether BNP can increase energy expenditure and improve glucose tolerance. Since recombinant human BNP is an FDA-approved drug prescribed for acute heart failure patients, the costs, and development and approval times for using BNP for these conditions may be reduced.

How does BNP work? Investigators in Italy almost 20 years ago discovered that binding sites for BNP, called natriuretic peptide receptors (NPRs), were expressed in human adipose tissue. The natriuretic peptide ‘signaling’ receptor, NPRA, binds the natriuretic peptides, while the natriuretic peptide ‘clearance’ receptor, NPRC, removes them from circulation. Since then, several studies have reported that BNP levels are lower in the blood of obese patients compared to their lean counterparts. Additional research suggests BNP can lead to increased release of adiponectin, an insulin-sensitizing hormone produced by fat cells and that low levels of BNP in the bloodstream might contribute to insulin resistance.

According to Collins, “Early studies proposed that increased clearance is responsible for the lower peptide levels observed in obese individuals in comparison to lean individuals; however, there are no definitive studies to actually prove this or not. Important efforts are currently underway to understand how NPRs are regulated and how the peptides can be best used for their fat-burning capacity.”

Dr. Sheila Collins is a professor at Sanford Burnham Prebys Medical Discovery Institute (SBP) in Lake Nona, Fla. and a recipient of an American Diabetes Association research award. Dr. Richard Pratley is a senior investigator at the Florida Hospital – SBP Translational Research Institute, Medical Director of the Florida Hospital Diabetes Institute, and adjunct professor at SBP in Lake Nona. This post was written by Crystal Woodard, PhD, a post-doctoral fellow in Dr. Collins’s lab.