Arbutus Biopharma and Vaccitech have signed a clinical trial collaboration agreement for an RNAi therapeutic plus immunotherapeutic to treat patients with chronic hepatitis B virus (HBV) infection (CHB).

The multi-centre Phase IIa trial will enrol patients who are on standard of care nucleos(t)ide reverse transcriptase inhibitor (NrtI) therapy.

It will assess the safety, pharmacokinetics, immunogenicity and antiviral activity of treatment with Arbutus’s GalNAc delivered RNAi therapeutic, AB-729, and then Vaccitech’s immunotherapeutic, VTP-300.

AB-729 blocks viral replication and mitigates all HBV antigens, including the hepatitis B surface antigen, in preclinical studies while VTP-300 is designed to induce an immune response against the virus.

Arbutus Biopharma chief development officer Gaston Picchio said: “We believe combining AB-729, which is designed to reduce HBsAg resulting in increased HBV immune responses with VTP-300, an immunotherapeutic designed to elicit an HBV specific immune response, may offer patients with CHB a much needed and durable functional cure.”

Arbutus will oversee the Phase IIa trial, which is set to launch in the second half of this year.

A joint development committee with both Arbutus and Vaccitech representatives will also supervise the study.

Yet to receive regulatory approval, the trial will recruit 40 NrtI-suppressed, hepatitis B e-antigen negative or positive, non-cirrhotic CHB patients, who will receive AB-729 plus NrtI for 24 weeks.

At week 24, participants will be given either NrtI plus VTP-300 or NrtI plus VTP-300 sham.

At week 48, all participants will be analysed for eligibility to discontinue all therapy or remain on their NrtI alone. Participants will be followed for another 48 weeks.

Arbutus and Vaccitech have complete rights to their respective candidates and will share all trial expenses.

Based on data from the Phase IIa trial, the companies plan to conduct a bigger Phase IIb study.

In March 2020, Arbutus reported positive preliminary data from a Phase Ia/Ib trial of AB-729 in healthy volunteers and patients with CHB on nucleos(t)ide antiviral treatment.