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Safety and Tolerability of Patisiran (ALN-TTR02) in Transthyretin (TTR) Amyloidosis

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ClinicalTrials.gov Identifier: NCT01617967
Recruitment Status : Completed
First Posted : June 13, 2012
Results First Posted : November 21, 2018
Last Update Posted : November 21, 2018
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

June 7, 2012
June 13, 2012
August 30, 2018
November 21, 2018
November 21, 2018
May 2012
October 2013   (Final data collection date for primary outcome measure)
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).
Safety and tolerability in ATTR patients [ Time Frame: Up to 56 Days ]
The proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs) and study drug discontinuation
Complete list of historical versions of study NCT01617967 on ClinicalTrials.gov Archive Site
  • Percentage Change From Baseline in Serum Transthyretin (TTR) Protein [ Time Frame: Baseline to Day 21/28 and Day 42/56 depending on dosing regimen (Q3W/Q4W) ]
    Percentage change of TTR relative to pretreatment/baseline levels is reported. For arms with a dosing regimen of Q4W TTR protein samples were measured on Days 28 and 56. For the arms with a dosing regimen of Q3W TTR protein samples were measured on Days 21 and 42.
  • Pharmacokinetic Parameters of Patisiran - Area Under the Concentration Curve From Time 0 to Last Measurable Time Point (AUC0-last) [ Time Frame: 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 profiles for patisiran (ALN-TTR02) were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.
  • Pharmacokinetic Parameters of Patisiran - Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 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 profiles for patisiran (ALN-TTR02) were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.
  • Pharmacokinetic Parameters of Patisiran - Beta Elimination Half-life (t1/2 Beta) [ Time Frame: 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 profiles for patisiran were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.
  • Pharmacokinetic Parameters of Patisiran - Systemic Clearance (CL) [ Time Frame: 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 profiles for patisiran were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.
  • Pharmacokinetic Parameters of Patisiran - Apparent Volume of Distribution at Steady State (Vss) [ Time Frame: 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 profiles for patisiran were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.
  • Pharmacokinetic Parameters of Patisiran - Renal Clearance (CLR) [ Time Frame: 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 profiles for patisiran were determined based on dosage and dosing frequency only, not premedication regimens. For arms with a dosing regimen of Q4W PK samples were taken on Days 0 and 28. For the arm with a dosing regimen of Q3W PK samples were taken on Days 0 and 21.
  • Pharmacokinetics (PK) of ALN-TTR02 [ Time Frame: Up to 208 days ]
    Cmax, Area Under Curve, Tmax
  • Serum transthyretin (TTR) protein [ Time Frame: Up to 208 days ]
    Determination of % Lowering to pretreatment/Baseline Levels
Not Provided
Not Provided
 
Safety and Tolerability of Patisiran (ALN-TTR02) in Transthyretin (TTR) Amyloidosis
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
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).
Not Provided
Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
TTR-mediated Amyloidosis
Drug: Patisiran
Participants received a single dose of patisiran as an intravenous (IV) infusion on Day 0 and Day 28 (Q4W). Optional cohorts received an alternative dosing regimen (once every 3 weeks [Q3W]: Day 0 and Day 21) and an alternative premedication regimen.
Other Name: ALN-TTR02
Experimental: 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: Drug: Patisiran
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
29
20
January 2014
October 2013   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years to 85 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Brazil,   France,   Germany,   Portugal,   Spain,   Sweden,   United States
 
 
NCT01617967
ALN-TTR02-002
2012-000467-24 ( EudraCT Number )
No
Studies a U.S. FDA-regulated Drug Product: Yes
Not Provided
Alnylam Pharmaceuticals
Alnylam Pharmaceuticals
Not Provided
Study Director: Jared Gollob, MD Alnylam Pharmaceuticals
Alnylam Pharmaceuticals
October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP