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

NCT01617967 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: ALN-TTR02-0022012-000467-24
• Study Type: interventional
• Target: 29
• Locations: 7 countries
• Sites: 10

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).

Conditions

TTR-mediated Amyloidosis

Keywords

RNAi therapeutic

Outcome Measures

Primary Outcomes (1)

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

  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).

  Up to 56 days post first dose

Secondary Outcomes (7)

• 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 - 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)

• 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 - 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

Study Arms (1)

Patisiran (ALN-TTR02)

EXPERIMENTAL

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.

Drug: Patisiran

Interventions

Patisiran DRUG

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.

Also known as: ALN-TTR02

Patisiran (ALN-TTR02)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alnylam Pharmaceuticals: lead

Study Sites (10)

Clinical Trial Site

Boston, Massachusetts, United States

Location

Clinical Trial Site

Rio de Janeiro, Brazil

Location

Clinical Trial Site

Le Kremlin-Bicêtre, France

Location

Clinical Trial Site

Marseille, France

Location

Clinical Trial Site

Münster, Germany

Location

Clinical Trial Site

Lisbon, Portugal

Location

Clinical Trial Site

Porto, Portugal

Location

Clinical Trial Site

Barcelona, Spain

Location

Clinical Trial Site

Palma de Mallorca, Spain

Location

Clinical Trial Site

Umeå, Sweden

Location

Related Publications (1)

• 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.

  PMID: 26338094 DERIVED

MeSH Terms

Interventions

patisiran

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Alnylam Pharmaceuticals, Inc.

medinfo@alnylam.com

1-877-256-9526

Study Officials

• Jared Gollob, MD

  Alnylam Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: June 7, 2012
• First Posted: June 13, 2012
• Study Start: May 1, 2012
• Primary Completion: October 1, 2013
• Study Completion: January 1, 2014
• Last Updated: April 19, 2024
• Results First Posted: November 21, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share

Locations

US (1); FR (2); PT (2); DE (1); ES (2); SE (1); BR (1)