New experimental therapy enters early human testing for hepatitis B
Trial will study safety and early effects in people with chronic HBV
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Dosing has begun in a Phase 1/2 clinical trial testing CRMA-1001, Nchroma Bio’s experimental epigenetic therapy being studied as a potential functional cure for chronic hepatitis B.
Epigenetic therapies work by adding chemical tags to DNA that can switch genes on or off without changing the DNA itself. CRMA-1001 — originally developed by Chroma Medicine before it merged with Nvelop Therapeutics to form Nchroma Bio — is designed to silence the DNA of the hepatitis B virus (HBV).
“We are proud to reach this important clinical milestone,” Jeff Walsh, Nchroma’s CEO, said in a company press release. “Dosing the first participant in our Phase 1/2 study is a key step toward evaluating CRMA-1001’s potential to provide clinically meaningful and durable responses for people living with chronic HBV [infection], a disease that affects hundreds of millions worldwide and for which existing treatments are rarely curative.”
How the early-stage study will work
The Phase 1/2 study (NCT07200193) aims to enroll up to 66 adults with chronic hepatitis B who are already taking oral antiviral medications. The study is currently recruiting at sites in Hong Kong and New Zealand, and is expected to expand to sites in the U.K.
The hepatitis B virus is spread by contact with bodily fluids and infects the liver, causing inflammation known as hepatitis. In some people, especially those infected in early life, HBV can lead to a long-lasting, chronic infection that increases the risk of serious complications, including liver cancer.
When HBV infects a cell, it delivers its DNA into the cell and hijacks the cell’s machinery to make viral proteins, which allows new virus particles to be produced and spread infection.
CRMA-1001 is designed to silence HBV DNA by adding chemical tags called methyl groups, which help switch off viral genes and block the production of new viral proteins.
The therapy targets two hard-to-eliminate forms of the virus’s genetic material: covalently closed circular DNA, which acts as a blueprint for making new virus, and viral DNA that has become integrated into a person’s own cells. These forms can allow the infection to persist even after years of treatment.
Nchroma hopes the therapy will offer a functional cure for chronic HBV infection. In hepatitis B research, a functional cure is generally defined as a sustained loss of detectable HBV DNA and the viral protein HBsAg for at least 24 weeks (about six months) after a finite course of treatment, allowing the immune system to control the virus without ongoing antiviral therapy.
What studies in animals have shown so far
In mouse models, CRMA-1001 treatment strongly reduced levels of the viral protein HBsAg, which plays an important role in helping HBV infect cells and evade the immune system.
In the first part of the ongoing Phase 1/2 trial, adults with chronic hepatitis B will receive either a single dose or multiple increasing doses of CRMA-1001, given through an infusion into the bloodstream. Up to four doses will be tested in combination with standard antiviral therapy.
Data from this part will be used to help identify the most appropriate dose to move forward into the study’s second, dose-expansion phase, which will include a larger group of participants.
The trial’s main goal is to evaluate the safety and tolerability of CRMA-1001 over the first six months of treatment. Secondary goals include assessing CRMA-1001’s pharmacological properties — how it behaves in the body — along with its effects on HBV-related biomarkers and longer-term outcomes such as functional cure, with participants followed for up to 60 months (about five years).
“Dosing the first participant underscores the progress we’ve made in advancing our highly optimized and potentially best-in-class epigenetic silencer,” said Jenny Marlowe, PhD, chief development officer at Nchroma. “We look forward to generating early clinical insights that will inform the future development of CRMA-1001 and potentially reshape the therapeutic landscape for chronic hepatitis B.”
