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Patisiran in Patients With Hereditary Transthyretin-mediated Amyloidosis (hATTR Amyloidosis) Disease Progression Post-Liver Transplant

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03862807
Recruitment Status : Active, not recruiting
First Posted : March 5, 2019
Last Update Posted : July 9, 2020
Sponsor:
Information provided by (Responsible Party):
Alnylam Pharmaceuticals

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

Condition or disease Intervention/treatment Phase
Amyloidosis, Familial Transthyretin Amyloidosis Drug: Patisiran Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Study to Evaluate Safety, Efficacy and Pharmacokinetics (PK) of Patisiran-LNP in Patients With Hereditary Transthyretin-mediated Amyloidosis (hATTR Amyloidosis) With Disease Progression Post-Orthotopic Liver Transplant
Actual Study Start Date : March 27, 2019
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2021

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Patisiran
Participants will receive patisiran during the Treatment Period.
 Drug: Patisiran
Patisiran will be administered by intravenous (IV) infusion.
Other Name: ALN-TTR02


Outcome Measures
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Primary Outcome Measures :
  1. Average of Month 6 and Month 12 Percentage Reduction from Baseline in Serum Transthyretin (TTR) [ Time Frame: Baseline, Months 6 and 12 ]

Secondary Outcome Measures :
  1. Change from Baseline in the Neuropathy Impairment Score (NIS) at Month 12 [ Time Frame: Baseline, Month 12 ]
    The NIS is a composite neurologic impairment score that assesses motor weakness (NIS-W), sensation (NIS-S) and reflexes (NIS-R) by physical exam. The minimum and maximum values are 0 and 244, respectively. A higher score indicates a worse outcome.

  2. Change from Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Score at Month 12 [ Time Frame: Baseline, Month 12 ]
    The Norfolk QoL-DN questionnaire is a standardized 35-item patient-reported outcomes measure that is sensitive to the different features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function. The minimum and maximum values are -4 and 136, respectively. A higher score indicates a worse outcome.

  3. Change from Baseline in the Rasch-Built Overall Disability Scale (R-ODS) at Month 12 [ Time Frame: Baseline, Month 12 ]
    The R-ODS is comprised of a 24-item linearly weighted scale that specifically captures activity and social participation limitations. The minimum and maximum values are 0 and 48, respectively. A higher score indicates a better outcome.

  4. Change from Baseline in the Composite Autonomic Symptom Score (COMPASS-31) at Month 12 [ Time Frame: Baseline, Month 12 ]
    The COMPASS-31 questionnaire is a measure of autonomic neuropathy symptoms. The questions evaluate 6 autonomic domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor). The minimum and maximum values are 0 and 100, respectively. A higher score indicates a worse outcome.

  5. Change from Baseline in the Modified Body Mass Index (mBMI) at Month 12 [ Time Frame: Baseline, Month 12 ]
  6. Percentage of Participants With Adverse Events [ Time Frame: From baseline to end of study at Month 13 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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 an other tetramer stabilizer during the study
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03862807


Locations
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France
Clinical Trial Site
Créteil, France
Clinical Trial Site
Le Kremlin-Bicêtre, France
Germany
Clinical Trial Site
Münster, Germany
Italy
Clinical Trial Site
Messina, Italy
Portugal
Clinical Trial Site
Porto, Portugal
Spain
Clinical Trial Site
Barcelona, Spain
Clinical Trial Site
Huelva, Spain
Sweden
Clinical Trial Site
Umeå, Sweden
United Kingdom
Clinical Trial Site
London, United Kingdom
Sponsors and Collaborators
Alnylam Pharmaceuticals
Investigators
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Study Director: Jing Jing Wang, MD Alnylam Pharmaceuticals
More Information
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Responsible Party: Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03862807    
Other Study ID Numbers: ALN-TTR02-008
2018-003519-24 ( EudraCT Number )
First Posted: March 5, 2019    Key Record Dates
Last Update Posted: July 9, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Amyloidosis, Familial
Amyloidosis
Disease Progression
Disease Attributes
Pathologic Processes
 Proteostasis Deficiencies
Metabolic Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn