Clinical trial NCT01617967: Safety and Tolerability of Patisiran (ALN-TTR02) in Transthyretin (TTR) Amyloidosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: TTR-mediated Amyloidosis
Keywords: RNAi therapeutic
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2012-06-13
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Study Drug Discontinuation
timeFrame: Up to 56 days post first dose
Secondary outcomes:
measure: Percentage Change From Baseline in Serum Transthyretin (TTR) Protein
timeFrame: Baseline to Day 21/28 and Day 42/56 depending on dosing regimen (Q3W/Q4W)
measure: Pharmacokinetic Parameters of Patisiran - Area Under the Concentration Curve From Time 0 to Last Measurable Time Point (AUC0-last)
timeFrame: 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)
measure: Pharmacokinetic Parameters of Patisiran - Maximum Observed Plasma Concentration (Cmax)
timeFrame: 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)
measure: Pharmacokinetic Parameters of Patisiran - Beta Elimination Half-life (t1/2 Beta)
timeFrame: 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
measure: Pharmacokinetic Parameters of Patisiran - Systemic Clearance (CL)
timeFrame: 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
measure: Pharmacokinetic Parameters of Patisiran - Apparent Volume of Distribution at Steady State (Vss)
timeFrame: 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
measure: Pharmacokinetic Parameters of Patisiran - Renal Clearance (CLR)
timeFrame: 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
Other outcomes:
Locations:
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Rio de Janeiro
country: Brazil
facility: Clinical Trial Site
city: Le Kremlin-bicetre
country: France
facility: Clinical Trial Site
city: Marseille Cedex
country: France
facility: Clinical Trial Site
city: Munster
country: Germany
facility: Clinical Trial Site
city: Lisbon
country: Portugal
facility: Clinical Trial Site
city: Porto
country: Portugal
facility: Clinical Trial Site
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Palma De Mallorca
country: Spain
facility: Clinical Trial Site
city: Umeå
country: Sweden
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Jared Gollob, MD
role: STUDY_DIRECTOR
References:
citation: Suhr OB, Coelho T, Buades J, Pouget J, Conceicao I, Berk J, Schmidt H, Waddington-Cruz M, Campistol JM, Bettencourt BR, Vaishnaw A, Gollob J, Adams D. Efficacy and safety of patisiran for familial amyloidotic polyneuropathy: a phase II multi-dose study. Orphanet J Rare Dis. 2015 Sep 4;10:109. doi: 10.1186/s13023-015-0326-6.