Clinical Trials

Date: 2016-07-09

Type of information: Treatment of the first patient

phase: 1-2

Announcement: treatment of the first patient

Company: Arrowhead Research Corporation (USA - CA)

Product: ARC-521

Action mechanism: RNAi/siRNA. ARC-521 is being investigated for its potential to produce functional cures in patients with chronic hepatitis B virus (HBV) infection. ARC-521 intervenes upstream of the reverse transcription process where current standard-of-care nucleotide and nucleoside analogs act, and is designed to silence the production of all HBV gene products. The small interfering RNAs (siRNAs) in ARC-521 engage the body's normal cellular RNAi machinery and direct specific cleavage of HBV RNA transcripts, thereby reducing the levels of HBV proteins and the RNA template used to produce viral DNA. Designed to complement ARC-520, ARC-521 targets HBV mRNA transcripts from both cccDNA and integrated DNA and is expected to be most suitable for those patients who tend to have lower levels of viral cccDNA.

Disease: chronic hepatitis B

Therapeutic area: Infectious diseases

Country: New Zealand

Trial details: The ARC-521 study (ARC5211001) is a multicenter, placebo-controlled, double-blind, dose escalation study of ARC-521 in healthy volunteers including a sequential, multiple dose, open label part in patients with chronic HBV. Normal healthy volunteers will enroll sequentially into a total of 6 escalating dose levels (6 subjects per dose level), randomized to receive a single dose of ARC-521 or placebo. Chronic HBV patients that are negative for Hepatitis B e-antigen (HBeAg) at screening will enroll sequentially into 3 dose levels (8 patients per dose level) to receive 3 monthly doses of open label ARC-521. The study is currently recruiting at a single center in New Zealand and the company plans to add additional centers in other countries, pending regulatory and ethics review. (NCT02797522)

Latest news:

• • On July 9, 2016, Arrowhead Pharmaceuticals announced that it has dosed the first patient in the multiple ascending dose (MAD) portion of the ongoing Phase 1/2 study of ARC-521, its second RNAi-based investigational medicine for the treatment of chronic hepatitis B virus (HBV) infection. To date 24 healthy volunteers have been treated in the study, and the drug safety committee (DSC) approved initiation of the MAD after a planned review of safety data from cohort 3 of the healthy volunteer portion of the study.
• • On June 9, 2016, Arrowhead Pharmaceuticals announced that it initiated a Phase 1/2 study of ARC-521, the company's second RNAi-based investigational medicine for the treatment of chronic hepatitis B virus (HBV) infection. The study is designed to evaluate the safety, tolerability, and pharmacokinetics of single doses of ARC-521 in healthy volunteers and the safety, tolerability, and antiviral activity of single and multiple doses of ARC-521 in patients with chronic HBV. This study may have multiple readouts, including single dose safety data, single dose antiviral activity data, and multiple dose safety and antiviral activity data.
• • On April 28, 2016, Arrowhead Pharmaceuticals announced that the company recently filed a regulatory submission in New Zealand to begin a Phase 1/2 clinical trial of ARC-521, its RNAi-based therapeutic candidate for the treatment of chronic hepatitis B virus (HBV) infection. Pending approval, Arrowhead intends to proceed with ARC521-1001, a first-in-human study to assess single and multiple-doses of ARC-521 in healthy volunteers and HBV patients. The application for approval of a clinical trial was submitted to the New Zealand Medicines and Medical Devices Safety Authority (MEDSAFE) for review by the Standing Committee on Therapeutic Trials (SCOTT). Arrowhead also intends to seek regulatory clearance to conduct ARC521-1001 in additional countries.

Is general: Yes