Clinical Trials List
Protocol NumberALN-TTR02-006
NCT Number(ClinicalTrials.gov Identfier)NCT02510261
2016-04-01 - 2023-06-30
Phase III
Terminated2
ICD-10G63
Polyneuropathy in diseases classified elsewhere
ICD-10G65.0
Sequelae of Guillain-Barre syndrome
ICD-10G65.1
Sequelae of other inflammatory polyneuropathy
ICD-10G65.2
Sequelae of toxic polyneuropathy
ICD-9357.4
Polyneuropathy in other diseases classified elsewhere
A Multicenter, Open-Label, Extension Study to Evaluate the Long-term Safety and Efficacy of Patisiran in Patients with Familial Amyloidotic Polyneuropathy Who Have Completed a Prior Clinical Study with Patisiran
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Trial Applicant
MEDPACE TAIWAN LIMITED
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Sponsor
Alnylam Pharmaceutical Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Kon-Ping Lin Division of Neurology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- SUNG-TSANG HSIEH Division of Neurology
- Ming-Jen Lee Division of Neurology
- LI-KAI TSAI Division of Neurology
- 楊智超 Division of Neurology
- SHIN-JOE YEH Division of Neurology
- Jen Jen and I Su Division of Neurology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
ATTR patients with symptomatic polyneuropathy (FAP)
Objectives
To assess the safety and efficacy of long-term dosing with patisiran in transthyretin-mediated
amyloidosis (ATTR) patients with familial amyloidotic polyneuropathy (FAP).
Test Drug
Patisiran
Active Ingredient
siRNA ALN-18328
Dosage Form
Injection
Dosage
2 mg/mL, 5.5mL/vial
Endpoints
Primary Outcome Measures :
1. Safety and tolerability of long-term dosing of patisiran as measured by the proportion of subjects with adverse events leading to discontinuation of study drug [ Time Frame: 52 weeks ]
Secondary Outcome Measures :
1. Assessment of changes from baseline in neurologic impairment assessed using the Neuropathy Impairment Score (NIS) associated with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
2. Assessment of changes from baseline in neurologic impairment assessed using the Modified NIS (mNIS +7) composite score associated with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
3. Assessment of changes from baseline in neurologic impairment assessed using NIS+7 associated with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
4. Assessment of changes from baseline in quality of life using the Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) questionnaire associated with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
5. Assessment of changes from baseline in quality of life using the EuroQOL (EQ-5D) questionnaire associated with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
6. Assessment of changes from baseline in autonomic function assessed using the Composite Autonomic Symptom Score (COMPASS 31) with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
7. Assessment of changes from baseline in serum TTR lowering associated with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
8. Assessment of changes from baseline in nutritional status using modified body mass index (mBMI) associated with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
9. Assessment of changes from baseline in disability reported by patients using the Rasch-built Overall Disability Scale (R-ODS) associated with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
10. Assessment of changes from baseline in motor function assessed by NIS-Weakness (NIS-W) with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
11. Assessment of changes from baseline in motor function assessed by timed 10-meter walk test with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
12. Assessment of changes from baseline in motor function assessed by grip strength test with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
1. Safety and tolerability of long-term dosing of patisiran as measured by the proportion of subjects with adverse events leading to discontinuation of study drug [ Time Frame: 52 weeks ]
Secondary Outcome Measures :
1. Assessment of changes from baseline in neurologic impairment assessed using the Neuropathy Impairment Score (NIS) associated with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
2. Assessment of changes from baseline in neurologic impairment assessed using the Modified NIS (mNIS +7) composite score associated with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
3. Assessment of changes from baseline in neurologic impairment assessed using NIS+7 associated with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
4. Assessment of changes from baseline in quality of life using the Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) questionnaire associated with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
5. Assessment of changes from baseline in quality of life using the EuroQOL (EQ-5D) questionnaire associated with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
6. Assessment of changes from baseline in autonomic function assessed using the Composite Autonomic Symptom Score (COMPASS 31) with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
7. Assessment of changes from baseline in serum TTR lowering associated with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
8. Assessment of changes from baseline in nutritional status using modified body mass index (mBMI) associated with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
9. Assessment of changes from baseline in disability reported by patients using the Rasch-built Overall Disability Scale (R-ODS) associated with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
10. Assessment of changes from baseline in motor function assessed by NIS-Weakness (NIS-W) with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
11. Assessment of changes from baseline in motor function assessed by timed 10-meter walk test with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
12. Assessment of changes from baseline in motor function assessed by grip strength test with long-term dosing of patisiran [ Time Frame: baseline, week 52 ]
Inclution Criteria
Patient Inclusion Criteria
To be enrolled in the study, patients must meet the following criteria before administration of
patisiran on Day 0:
1. Have completed a patisiran study (ie, completed the last efficacy visit in the parent study)
and, in the opinion of the investigator, tolerated study drug
2. Be considered fit for the study by the Investigator
3. Have aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤2.5 × the
upper limit of normal (ULN), international normalized ratio (INR) ≤2.0 (patients on
anticoagulant therapy with an INR of ≤3.5 will be allowed)
4. Have a total bilirubin within normal limits. A patient with total bilirubin ≤ 2 X ULN is
eligible if the elevation is secondary to documented Gilbert’s syndrome (elevation of
unconjugated bilirubin with normal conjugated bilirubin) and the patient has ALT and AST
levels within normal ranges.
5. Have a serum creatinine ≤2 × ULN
6. Women of child-bearing potential must have a negative pregnancy test, cannot be
breastfeeding, and must be using 2 highly effective methods of contraception prior to
dosing in this study and agree to use 2 highly effective methods of contraception
throughout study participation and for 75 days after last dose of patisiran in this study.
Highly effective methods of birth control are defined in Section 4.4.
7. Males with partners of child-bearing potential must agree to use 1 barrier method
(eg, condom) and 1 additional method (eg, spermicide) of contraception throughout study
participation and for 75 days after the last dose of patisiran in this study; males must also
abstain from sperm donation after the first dose of patisiran through study participation
and for 75 days after last dose of patisiran in this study
8. Be willing and able to comply with the protocol-required visit schedule and visit
requirements and provide written informed consent
To be enrolled in the study, patients must meet the following criteria before administration of
patisiran on Day 0:
1. Have completed a patisiran study (ie, completed the last efficacy visit in the parent study)
and, in the opinion of the investigator, tolerated study drug
2. Be considered fit for the study by the Investigator
3. Have aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤2.5 × the
upper limit of normal (ULN), international normalized ratio (INR) ≤2.0 (patients on
anticoagulant therapy with an INR of ≤3.5 will be allowed)
4. Have a total bilirubin within normal limits. A patient with total bilirubin ≤ 2 X ULN is
eligible if the elevation is secondary to documented Gilbert’s syndrome (elevation of
unconjugated bilirubin with normal conjugated bilirubin) and the patient has ALT and AST
levels within normal ranges.
5. Have a serum creatinine ≤2 × ULN
6. Women of child-bearing potential must have a negative pregnancy test, cannot be
breastfeeding, and must be using 2 highly effective methods of contraception prior to
dosing in this study and agree to use 2 highly effective methods of contraception
throughout study participation and for 75 days after last dose of patisiran in this study.
Highly effective methods of birth control are defined in Section 4.4.
7. Males with partners of child-bearing potential must agree to use 1 barrier method
(eg, condom) and 1 additional method (eg, spermicide) of contraception throughout study
participation and for 75 days after the last dose of patisiran in this study; males must also
abstain from sperm donation after the first dose of patisiran through study participation
and for 75 days after last dose of patisiran in this study
8. Be willing and able to comply with the protocol-required visit schedule and visit
requirements and provide written informed consent
Exclusion Criteria
Patient Exclusion Criteria
A patient will be excluded if they meet any of the following criteria before dosing at the Day 0:
1. Has an active infection requiring systemic antiviral or antimicrobial therapy that will not
be completed before the first dose of patisiran administration
2. Has poorly controlled diabetes mellitus
3. Has uncontrolled cardiac arrhythmia or unstable angina
4. Is currently taking tafamidis, diflunisal, doxycycline, or tauroursodeoxycholic acid
(TUDCA), unless previously allowed per the parent study
5. Is unable to take the required premedications, unless modifications to the premedication
regimen were previously allowed per the parent study
6. Is under legal protection (defined as “any person who becomes incapable of protecting
his/her interests due to a medically diagnosed impairment of his/her mental faculties that
may limit or prevent the expression of his will”), decided by a court
A patient will be excluded if they meet any of the following criteria before dosing at the Day 0:
1. Has an active infection requiring systemic antiviral or antimicrobial therapy that will not
be completed before the first dose of patisiran administration
2. Has poorly controlled diabetes mellitus
3. Has uncontrolled cardiac arrhythmia or unstable angina
4. Is currently taking tafamidis, diflunisal, doxycycline, or tauroursodeoxycholic acid
(TUDCA), unless previously allowed per the parent study
5. Is unable to take the required premedications, unless modifications to the premedication
regimen were previously allowed per the parent study
6. Is under legal protection (defined as “any person who becomes incapable of protecting
his/her interests due to a medically diagnosed impairment of his/her mental faculties that
may limit or prevent the expression of his will”), decided by a court
The Estimated Number of Participants
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Taiwan
21 participants
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Global
230 participants
