Amyloidogenic Transthyretin (ATTR) Amyloidosis Clinical Trial
Official title:
A Phase 1, Open-label, Dose Escalation Study of Intravenous PRX004 in Subjects With Amyloid Transthyretin (ATTR) Amyloidosis
A Phase 1, open-label study of intravenous (IV) PRX004 as a single agent in subjects with hereditary amyloid transthyretin (hATTR) amyloidosis. The study will consist of 3 phases and will enroll up to a total of 36 subjects. A 3+3 dose escalation component to determine the safety, tolerability, PK, PD, and MTD. An expansion component in anticipated PRX004 RP2D cohorts selected from the Dose Escalation Phase. An extended dosing component for eligible subjects from the Dose Escalation or Expansion phases.
This Phase 1, open-label consists of 3 phases. The Dose Escalation Phase is a 3+3 dose
escalation component to determine the safety, tolerability, PK, PD, and MTD of IV PRX004 when
given as a single agent in up to 36 evaluable subjects with hATTR amyloidosis. The Expansion
Phase is an expansion component in anticipated PRX004 RP2D cohorts selected from the Dose
Escalation Phase (this may occur in addition to cohorts in which additional subjects were
added due to the observation of a dose-limiting [DLT] in the Escalation Phase). The Long-term
Extension (LTE) Phase is an extended dosing component for eligible subjects from the Dose
Escalation or Expansion phases.
The Dose Escalation Phase will follow a standard 3+3 design, in which cohorts of 3 to 6
subjects with hATTR amyloidosis will be enrolled at each dose level to receive IV PRX004 once
every 28 days, based on scheduling from Month 1-Day 1 for up to 3 doses. Each subject will
participate in only 1 dose escalation cohort. The starting dose of PRX004 will be 0.1 mg/kg.
Dose escalation will occur after the third evaluable subject in a cohort has completed the
first 28 days following the first administration of PRX004. Up to 6 dose levels of PRX004 may
be investigated (0.1, 0.3, 1, 3, 10, and 30 mg/kg) if tolerable. In the event the starting
dose of 0.1 mg/kg is not tolerated, the dose escalationwill be halted and the study stopped.
Each subject will receive a maximum of 3 infusions of PRX004 in the Dose Escalation Phase.
Subjects who complete the Month 3-Day 22 Visit in the Dose Escalation or Expansion phases may
be eligible to receive up to 15 additional PRX004 infusions in the LTE Phase.
Each subject will receive a maximum of 3 infusions of PRX004 in the Dose Escalation Phase.
Subjects who complete the Month 3-Day 22 Visit in the Dose Escalation or Expansion phases may
be eligible to receive up to 15 additional PRX004 infusions in the LTE Phase.
Subjects who completed the EOS Visit in the Dose Escalation Phase prior to implementation of
Protocol Amendment 2 may re-enter the study in the LTE Phase if they meet specific
inclusion/exclusion criteria.
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