The Study of an Investigational Drug, Revusiran (ALN-TTRSC), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis in Patients Whose Disease Has Continued to Worsen Following Liver Transplant
- Conditions
- ATTR AmyloidosisTransthyretin (TTR)-Mediated AmyloidosisFamilial Amyloidotic Polyneuropathy (FAP)Familial Amyloid Neuropathies
- Interventions
- Registration Number
- NCT02595983
- Lead Sponsor
- Alnylam Pharmaceuticals
- Brief Summary
The purpose of this study was to evaluate the safety and effectiveness of revusiran (ALN-TTRSC) in adults with transthyretin-mediated amyloidosis (ATTR), whose disease has continued to worsen after liver transplantation. Dosing has been discontinued; patients are being followed-up for safety.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
- Diagnosis of FAP (familial amyloidotic polyneuropathy) with documented TTR mutation
- Received an orthotopic liver transplant ≥12 months before the date of informed consent
- An increase in polyneuropathy disability (PND) score post-transplant
- Polyneuropathy Disability score of ≤3b
- New York Heart Association (NYHA) classification of >2
- Other known causes of sensorimotor or autonomic neuropathy (eg, autoimmune disease)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description All Patients Revusiran All patients who received at least 1 dose of revusiran (ALN-TTRSC)
- Primary Outcome Measures
Name Time Method Percentage Change From Baseline in Serum TTR at Month 6 Month 6 A negative percentage change from baseline at Month 6 indicates a reduction in serum TTR level.
- Secondary Outcome Measures
Name Time Method Percentage Change From Baseline in Serum TTR Over 18 Months Weeks 3, 7, 12, 18, 24, 26 (Month 6), 39 (Month 9), 52 (Month 12), 57, 78 (Month 18) A negative percentage change from baseline indicates a reduction in serum TTR level.
Number of Participants in Each Polyneuropathy Disability (PND) Stage Based on Worst Post-Baseline Score Baseline, Months 6, 12, 18 PND Scores: Stage 0: No symptoms, Stage 1: Sensory disturbances but preserved walking capabilities, Stage 2: Impaired walking capacity, but ability to walk without a stick or crutches, Stage 3A/B: Walking with help of 1 or 2 sticks or crutches, Stage 4: confined to wheel chair. For each stage (0-4) at baseline, the number of participants is presented at their worst post-baseline score for each stage (0-4) post-baseline. Worst post-baseline is defined the highest PND classification for a participant recorded after the first dose of study drug.
Change From Baseline in Modified Neurological Impairment Score (mNIS +7) Composite Score Over 18 Months Baseline, Months 6, 12, 18 The mNIS+7 is a composite score that measures neurologic impairment which includes the following components: physical exam of lower limbs, upper limbs and cranial nerves to assess motor strength/weakness, electrophysiologic measurement of small and large nerve fiber function, sensory testing and postural blood pressure. The minimum and maximum values are 0 and 304, respectively. A higher score indicates a worse outcome. A negative change from baseline indicates an improvement.
Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) Questionnaire Score Baseline, Months 6, 12, 18 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.
Trial Locations
- Locations (2)
Clinical Trial SIte
🇬🇧London, United Kingdom
Clinical Trial Site
🇸🇪Umea, Sweden