Phase 3 Trial to Assess Shire’s Adynovate for Better Bleed Protection

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

Share this article:

Share article via email
AMT-061 gene therapy

Shire has launched a Phase 3 clinical trial (NCT02585960) with Adynovate, a drug approved to help treat and control bleeding in children and adults with hemophilia A. The trial is currently recruiting participants.

Adynovate is an injectable recombinant factor VIII (FVIII), designed using pegylation technology, which allows it to last longer in blood circulation, therefore requiring less frequent injections. Specifically, Adynovate is bound to a molecule called polyethylene glycol, or PEG, and in this manner lasts 40% to 50% longer in the body than its counterpart molecule without PEG (called Advate).

The U.S. Food and Drug Administration (FDA) approved Adynovate in November 2015 as a treatment for adults and adolescents who are at least 12 years old who have hemophilia A. In 2016, the FDA extended Adynovate’s clinical approval for as-needed treatment and to control bleeding episodes in children younger than 12. The approval also included its use as routine preventive treatment to reduce the frequency of bleeding episodes in children younger than 12 and for perioperative management in adults and children.

The new Phase 3 trial is a prospective, randomized, multi-center clinical study to investigate both the effectiveness and safety of Adynovate after pharmacokinetics-guided preventive treatment in patients with severe hemophilia A. The study participants are ages 12 to 65.

Pharmacokinetics is a key branch in pharmacology that determines the time course of drug absorption, distribution, metabolism, and excretion. This type of study is important to achieve and improve a drug’s therapeutic effect.

In this clinical trial, researchers will first perform a pharmacokinetic evaluation of Adynovate, after which participants will be randomized to one of two dosing regimens: in the first regimen – the standard treatment arm – study participants will be treated with Adynovate twice a week. In a second regimen – the intensified treatment arm – participants be dosed every other day.

The trial’s primary outcome is to study the presence or absence of any bleeding periods in the second six-month study period. Secondary outcomes include assessing patients’ annualized bleeding rate (ABR) in the 12-month trial period.

This study will determine whether performing a personalized, pharmacokinetic-guided dosing of Adynovate targeting FVIII trough levels of 1-3% and 8-12% can increase the number of patients that achieve zero bleeds.