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

Transthyretin Amyloidosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03862807
• Other study ID #: ALN-TTR02-008
• Secondary ID: 2018-003519-24
• Status: Completed
• Phase: Phase 3
• Start date: March 27, 2019
• Est. completion date: October 20, 2020

Study information

• Verified date: November 2021
• Source: Alnylam Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: October 20, 2020
• Est. primary completion date: October 6, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 another tetramer stabilizer during the study

Related Conditions & MeSH terms

• Amyloidosis
• Amyloidosis, Familial
• Disease Progression
• Transthyretin Amyloidosis

Intervention

Drug:
• Patisiran
Patisiran was administered via IV infusion.

Locations

Country	Name	City	State
France	Clinical Trial Site	Créteil
France	Clinical Trial Site	Le Kremlin-Bicêtre
Germany	Clinical Trial Site	Münster
Italy	Clinical Trial Site	Messina
Portugal	Clinical Trial Site	Porto
Spain	Clinical Trial Site	Barcelona
Spain	Clinical Trial Site	Huelva
Sweden	Clinical Trial Site	Umeå
United Kingdom	Clinical Trial Site	London

Sponsors (1)

Lead Sponsor	Collaborator
Alnylam Pharmaceuticals

Countries where clinical trial is conducted

France,  Germany,  Italy,  Portugal,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change From Baseline in the Neuropathy Impairment Score (NIS) at 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.	Baseline, Month 12
Secondary	Change From Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Score at 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.	Baseline, Month 12
Secondary	Change From Baseline in the Rasch-Built Overall Disability Scale (R-ODS) at 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.	Baseline, Month 12
Secondary	Change From Baseline in the Composite Autonomic Symptom Score (COMPASS-31) at 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.	Baseline, Month 12
Secondary	Change From Baseline in the Modified Body Mass Index (mBMI) at Month 12	Nutritional status of participants was evaluated using the mBMI, calculated as BMI (kg/m^2) multiplied by albumin (g/L). An increase from baseline in mBMI suggests improvement, and a decrease from baseline suggests worsening.	Baseline, Month 12
Secondary	Percentage of Participants With Adverse Events	An AE is any untoward medical occurrence in a participant or clinical investigational patient administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.	From baseline to end of study at Month 13