Trial of HBV treatment candidate now enrolling final patient group
Phase 1b study testing VRON-0200 in adults with chronic hepatitis B
Virion Therapeutics has announced that it’s completed enrollment for the first two groups of adults with chronic hepatitis B virus (HBV) infection in the first clinical trial evaluating its immunotherapy VRON-0200 as a treatment for HBV.
Altogether, more than two dozen people with chronic hepatitis B have now been dosed with a VRON-0200 injection, according to a company press release.
Enrollment in the third and final group of patients in the Phase 1b clinical trial (NCT06070051) — which is taking place in New Zealand and Hong Kong — is now underway. This group is stated to receive VRON-0200 in combination with two other therapy candidates, elebsiran and tobevibart.
“The swift completion of enrollment of these two [groups], in this Phase 1b trial, reflects the strong interest among both providers and patients for finding an effective immunotherapy for chronic HBV that is safe, well tolerated, and easy to administer,” said Sue Currie, PhD, chief operating officer at Virion.
Specifically, 27 chronic hepatitis B patients on standard antiviral therapy have now received a single (prime) or a prime and booster dose of the candidate therapy. Previously announced results from the first 25 treated patients, most of whom were infected at birth, showed that a single dose was well tolerated and reduced signs of viral activity.
“What makes VRON-0200 so promising is its simplicity of administration (a single-, or two-injection regimen), its safety and tolerability profile, and now its documented anti-HBV activity, even in the most difficult [chronic hepatitis B] patient population — those infected at birth,” Currie said.
Experimental HBV treatment administered with 1- or 2-time injection
Hepatitis B is a type of liver inflammation caused by an HBV infection. For most people, the virus clears from the body, typically through the activity of HBV-specific CD8-positive T-cells — a type of immune cells also called cytotoxic T-cells because they kill infected cells.
Some patients, however, can’t clear the initial infection, and their T-cells soon become exhausted, losing their ability to fight the virus. This can lead to chronic or long-lasting infection, which can pave the way for serious problems like liver failure and liver cancer.
Standard treatment for chronic hepatitis B involves a class of antiviral medications called nucleos(t)ide analogs, which prevent the virus from replicating. Other first-line treatments include those based on interferons, which are immune proteins that help the body’s immune system fight infections.
“The addition of pegylated interferon (Peg-IFN), an immunomodulatory agent, plus investigational agents that potently suppress HBV, when added to standard of care nucleos(t)ide antiviral therapy, can maintain viral suppression in a large percentage of patients after discontinuation of therapy,” Currie said.
However, according to Currie, the use of Peg-IFN “has treatment challenges that can include high rates of adverse events, and convenience-related issues, such as a long duration of treatment.”
VRON-0200 is an immunotherapy administered by a one- or two-time injection into the muscle, with the goal of providing not just treatment, but a functional cure for chronic HBV infection.
The therapy is designed to amplify T-cell responses, particularly in cells not normally activated during chronic infection, which are less susceptible to exhaustion. This promotes further cytotoxic T-cell expansion and improves viral control, according to Virion.
The injections are delivered using a chimpanzee-derived adenovirus, against which the human immune system has limited reactivity.
In preclinical studies, VRON-0200 boosted the number of cytotoxic T-cells in a mouse model of hepatitis B, which strongly correlated with reduced HBV DNA viral load in blood.
Trial of VRON-0200 underway at 3 sites in Hong Kong and New Zealand
The ongoing Phase 1b clinical trial is evaluating the safety, tolerability, and immune effects of prime dosing alone, and prime plus boost dosing, of VRON-0200. The study, being conducted at two sites in New Zealand and one in Hong Kong, will overall involve an estimated 56 people, ages 18-55, with chronic HBV infection.
To be eligible, patients must be free of cirrhosis, or permanent liver scarring, but can test positive or negative for HBeAg, an HBV protein that indicates the virus is actively replicating in the body.
Participants must also have been on nucleos(t)ide antiviral therapy for at least a year, with HBV DNA levels less than 40 international units per milliliter (IU/mL) and HBsAg levels up to 500 IU/mL. A marker of viral load, HBsAg is a protein critical for HBV’s ability to infect cells and escape the immune system.
A total of 27 patients enrolled in the first, low-dose group and second, high-dose group have randomly received either a prime dose alone or a prime plus a boost dose.
Enrollment is ongoing for the third group, which will include patients with up to 1,000 IU/mL of HBsAg. These participants will be randomly assigned to receive a VRON-0200 prime dose plus six monthly doses of the experimental therapies elebsiran and tobevibart, starting on day 28, either alone or with a VRON-0200 boost on day 196, or at about the six-month mark. Elebsiran and tobevibart will be administered by subcutaneous, or under-the-skin, injections.
In addition to safety, efficacy measures include changes in blood levels of cytotoxic T-cells and HBV DNA, RNA, and HBsAg for up to one year.
[To date, the] findings highlight the potential of VRON-0200 as an [interferon-sparing] immunotherapy, alone or in combination, for HBV functional cure. … We look forward to sharing more VRON-0200 clinical data in 2025 and continuing to advance this clinical development program.
Early trial results from the first 25 patients who received a prime VRON-0200 dose showed the therapy was generally well tolerated, with no serious adverse events, treatment discontinuations, or laboratory abnormalities.
At that time, about one-third of the patients had experienced a 5.5 times increase in cytotoxic T-cell responses, “despite the fact that most patients had highly impaired HBV immunity prior to treatment,” Virion noted in the release.
Moreover, some patients also saw their HBsAg levels drop pronouncedly after one dose.
According to Currie, “these findings highlight the potential of VRON-0200 as an [interferon-sparing] immunotherapy, alone or in combination, for HBV functional cure.”
Currie added: “We look forward to sharing more VRON-0200 clinical data in 2025 and continuing to advance this clinical development program.”
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