A Phase 2, Open-Label, Multi-Dose, Dose Escalation Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous Infusions of ALN-TTR02 in Patients With TTR Amyloidosis

Alnylam Pharmaceuticals1 site in 1 country29 target enrollmentMay 2012

ConditionsTTR-mediated Amyloidosis

InterventionsPatisiran

DrugsPatisiran

Overview

Phase: Phase 2
Intervention: Patisiran
Conditions: TTR-mediated Amyloidosis
Sponsor: Alnylam Pharmaceuticals
Enrollment: 29
Locations: 1
Primary Endpoint: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug Discontinuation
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This was a multiple dose, dose escalation study designed to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of patisiran (ALN-TTR02) in participants with transthyretin (TTR) mediated amyloidosis (ATTR).

Registry

clinicaltrials.gov

Start Date

May 2012

End Date

January 2014

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Alnylam Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Body mass index must be between 17 kg/m\^2 and ≤ 33 kg/m\^2;
•Women of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must use appropriate contraception;
•Males agree to use appropriate contraception;
•Diagnosis of TTR amyloidosis;
•Adequate blood counts, liver and renal function;
•Willing to give written informed consent and are willing to comply with the study requirements.

Exclusion Criteria

•Known human immunodeficiency virus (HIV) positive status or known or suspected systemic bacterial, viral, parasitic, or fungal infection;
•Received an investigational agent, other than tafamidis or diflunisal, within 30 days prior to first dose study drug administration;
•Prior liver transplant;
•Poor cardiac function;
•Considered unfit for the study by the Principal Investigator;
•Employee or family member of the sponsor or the clinical study site personnel.

Arms & Interventions

Patisiran (ALN-TTR02)

Two administrations of patisiran will be administered once every 4 weeks \[Q4W\]) in 4 sequential cohorts with escalating doses followed by optional cohorts with an alternative dosing regimen (once every 3 weeks \[Q3W\]), and an alternative premedication regimen.

Intervention: Patisiran

Outcomes

Primary Outcomes

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug Discontinuation

Time Frame: Up to 56 days post first dose

The number of participants experiencing at least one adverse event (AE), at least one serious adverse event (SAE) and study drug discontinuation (due to any reason).

Secondary Outcomes

Pharmacokinetic Parameters of Patisiran - Renal Clearance (CLR)(Predose (within 1 h of planned dosing start) and post-infusion at 0-6 h (pooled) on Day 0 and Day 21/28 depending on dosing frequency)
Pharmacokinetic Parameters of Patisiran - Beta Elimination Half-life (t1/2 Beta)(Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing frequency)
Pharmacokinetic Parameters of Patisiran - Systemic Clearance (CL)(Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing frequency)
Percentage Change From Baseline in Serum Transthyretin (TTR) Protein(Baseline to Day 21/28 and Day 42/56 depending on dosing regimen (Q3W/Q4W))
Pharmacokinetic Parameters of Patisiran - Maximum Observed Plasma Concentration (Cmax)(Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing regimen (Q3W/Q4W))
Pharmacokinetic Parameters of Patisiran - Apparent Volume of Distribution at Steady State (Vss)(Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing frequency)
Pharmacokinetic Parameters of Patisiran - Area Under the Concentration Curve From Time 0 to Last Measurable Time Point (AUC0-last)(Predose, end of infusion and post-infusion at 5 minutes (min), 10 min, 30 min, 1 hour (h), 2 h, 4 h, 6 h, 24 h and 48 h on Day 0 and Day 21/28 depending on dosing regimen (Q3W/Q4W))