clinical trials Archives - Sanford Burnham Prebys

Tag: clinical trials

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

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.” 

Institute News

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.

Institute News

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.