Clinical trial NCT03862807: Patisiran in Patients With Hereditary Transthyretin-mediated Amyloidosis (hATTR Amyloidosis) Disease Progression Post-Liver Transplant
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Amyloidosis, Familial
Transthyretin Amyloidosis
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-03-05
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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 another tetramer stabilizer during the study

Primary outcomes:
measure: Average of Month 6 and Month 12 Percentage Reduction From Baseline in Serum Transthyretin (TTR)
timeFrame: Baseline, Months 6 and 12
Secondary outcomes:
measure: Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Score at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in the Rasch-Built Overall Disability Scale (R-ODS) at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in the Composite Autonomic Symptom Score (COMPASS-31) at Month 12
timeFrame: Baseline, Month 12
measure: Change From Baseline in the Modified Body Mass Index (mBMI) at Month 12
timeFrame: Baseline, Month 12
measure: Percentage of Participants With Adverse Events
timeFrame: From baseline to end of study at Month 13
Other outcomes:
Locations:
city: Créteil
country: France
facility: Clinical Trial Site
city: Le Kremlin-Bicêtre
country: France
facility: Clinical Trial Site
city: Münster
country: Germany
facility: Clinical Trial Site
city: Messina
country: Italy
facility: Clinical Trial Site
city: Porto
country: Portugal
facility: Clinical Trial Site
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Huelva
country: Spain
facility: Clinical Trial Site
city: Umeå
country: Sweden
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.