NCT03862807

Brief Summary

The purpose of this study is to evaluate the efficacy, safety and pharmacokinetics of patisiran in participants with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) with disease progression after liver transplant.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Mar 2019

Geographic Reach
7 countries

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 28, 2019

Completed
5 days until next milestone

First Posted

Study publicly available on registry

March 5, 2019

Completed
22 days until next milestone

Study Start

First participant enrolled

March 27, 2019

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 6, 2020

Completed
14 days until next milestone

Study Completion

Last participant's last visit for all outcomes

October 20, 2020

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

December 21, 2021

Completed
Last Updated

April 22, 2024

Status Verified

November 1, 2021

Enrollment Period

1.5 years

First QC Date

February 28, 2019

Results QC Date

October 6, 2021

Last Update Submit

April 17, 2024

Conditions

Amyloidosis, FamilialTransthyretin Amyloidosis

Outcome Measures

Primary Outcomes (1)

  • Average of Month 6 and Month 12 Percentage Reduction From Baseline in Serum Transthyretin (TTR)

    Serum TTR was assessed using enzyme linked immunosorbent assay (ELISA). The average of the percentage reduction in serum TTR observed at Month 6 and at Month 12 is first calculated for each patient and then the median (95% CI) of these averaged values is summarized for the Safety Analysis Set.

    Baseline, Months 6 and 12

Secondary Outcomes (6)

  • Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 12

    Baseline, Month 12

  • Change From Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Score at Month 12

    Baseline, Month 12

  • Change From Baseline in the Rasch-Built Overall Disability Scale (R-ODS) at Month 12

    Baseline, Month 12

  • Change From Baseline in the Composite Autonomic Symptom Score (COMPASS-31) at Month 12

    Baseline, Month 12

  • Change From Baseline in the Modified Body Mass Index (mBMI) at Month 12

    Baseline, Month 12

  • +1 more secondary outcomes

Study Arms (1)

Patisiran

EXPERIMENTAL

Participants received patisiran 0.3 milligrams/kilogram (mg/kg) via intravenous (IV) infusion once every 3 weeks (q3w) for 12 months. Dosing was based on actual body weight. For participants weighing 100 kg or more, patisiran was administered at a total dose of 30 mg IV q3w.

Drug: Patisiran

Interventions

PatisiranDRUG

Patisiran was administered via IV infusion.

Also known as: ALN-TTR02, ONPATTRO
Patisiran

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Received liver transplant for treatment of hATTR amyloidosis ≥12 months before study start
  • Has increase in polyneuropathy disability (PND) score after liver transplant
  • Has received stable immunosuppressive regimen with ≤10 mg/day of prednisone for at least 3 months before study start
  • Has Karnofsky Performance Status (KPS) of ≥70%
  • Has vitamin A level greater than or equal to lower limit of normal

You may not qualify if:

  • Has previously received inotersen or patisiran
  • Has clinically significant liver function test abnormalities
  • Has known portal hypertension with ascites
  • Has estimated glomerular filtration rate (eGFR) ≤30 mL/min/1.73 m\^2
  • Has known leptomeningeal amyloidosis
  • Has infection with hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
  • Has New York Heart Association heart failure classification of \>2
  • Is wheelchair bound or bedridden
  • Has received organ transplants other than liver transplant
  • Will be using another tetramer stabilizer during the study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Clinical Trial Site

Créteil, France

Location

Clinical Trial Site

Le Kremlin-Bicêtre, France

Location

Clinical Trial Site

Münster, Germany

Location

Clinical Trial Site

Messina, Italy

Location

Clinical Trial Site

Porto, Portugal

Location

Clinical Trial Site

Barcelona, Spain

Location

Clinical Trial Site

Huelva, Spain

Location

Clinical Trial Site

Umeå, Sweden

Location

Clinical Trial Site

London, United Kingdom

Location

Related Publications (3)

  • Badri P, Habtemariam B, Melch M, Clausen VA, Arum S, Li X, Jay PY, Vest J, Robbie GJ. Pharmacokinetics and Pharmacodynamics of Patisiran in Patients with hATTR Amyloidosis and with Polyneuropathy After Liver Transplantation. Clin Pharmacokinet. 2023 Oct;62(10):1509-1522. doi: 10.1007/s40262-023-01292-w. Epub 2023 Aug 28.

    PMID: 37639169DERIVED

  • Schmidt HH, Wixner J, Plante-Bordeneuve V, Munoz-Beamud F, Llado L, Gillmore JD, Mazzeo A, Li X, Arum S, Jay PY, Adams D; Patisiran Post-LT Study Group. Patisiran treatment in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy after liver transplantation. Am J Transplant. 2022 Jun;22(6):1646-1657. doi: 10.1111/ajt.17009. Epub 2022 Mar 26.

    PMID: 35213769DERIVED

  • Seibert K, Wlodarski R, Sarswat N, Appelbaum D, Issa NP, Soliven B, Rezania K. Progressive Multiple Mononeuropathy in a Patient With Familial Transthyretin Amyloidosis After Liver Transplantation. J Clin Neuromuscul Dis. 2022 Mar 1;23(3):143-147. doi: 10.1097/CND.0000000000000368.

    PMID: 35188911DERIVED

MeSH Terms

Conditions

Amyloidosis, FamilialAmyloidosis, Hereditary, Transthyretin-Related

Interventions

patisiran

Condition Hierarchy (Ancestors)

Metabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMetabolic DiseasesNutritional and Metabolic DiseasesAmyloidosisProteostasis Deficiencies

Results Point of Contact

Title
Chief Medical Officer
Organization
Alnylam Pharmaceuticals Inc.
clinicaltrials@alnylam.com
866-330-0326

Study Officials

  • Medical Director

    Alnylam Pharmaceuticals

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 28, 2019

First Posted

March 5, 2019

Study Start

March 27, 2019

Primary Completion

October 6, 2020

Study Completion

October 20, 2020

Last Updated

April 22, 2024

Results First Posted

December 21, 2021

Record last verified: 2021-11

Data Sharing

IPD Sharing
Will share

Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the US and/or the EU. Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Requests for access to data can be submitted via the website www.vivli.org.

Locations

IT(1)PT(1)DE(1)SE(1)FR(2)ES(2)GB(1)