Transthyretin (TTR)-mediated Familial Amyloidotic Polyneuropathy (FAP) MedDRA version: 18.0 Level: PT Classification code 10019889 Term: Hereditary neuropathic amyloidosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Revusiran
Product Code: ALN-TTRSC
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ALN-51547
Current Sponsor code: ALN-51547
Concentration unit: mg/ml milligram(s)/millil
Sponsors
Alnylam Pharmaceuticals, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female =18 years of age 2. Diagnosis of FAP with documented TTR mutation 3. Received an OLT =12 months before the date of informed consent 4. An increase in polyneuropathy disability (PND) score compared to a preliver transplant assessment OR increase in PND score between any 2 assessments postliver transplant, which in the opinion of the Investigator is due to underlying FAP progression 5. On stable immunosuppressive regimen with =10 mg/day of prednisone for at least 3 months before the date of informed consent 6. Neurological impairment score (NIS) of 5 to 130 (inclusive) 7. Polyneuropathy Disability score of =3b 8. Karnofsky Performance Status =60% 9. No liver allograft rejection episodes (chronic, acute, or subacute) in the past 6 months before the date of informed consent 10. Normal liver function, including aspartate transaminase, alanine transaminase, and total bilirubin, unless elevation in total bilirubin is due to Gilbert’s syndrome based on central laboratory evaluation 11. Adequate renal function demonstrated by estimated glomerular filtration rate =45 mL/min/1.73 m2 (calculated by a central laboratory using the Modification of Diet in Renal Disease formula) 12. Women of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must be willing to use 1 highly effective method of contraception throughout study participation and for 28 days after last dose administration 13. Males who agree to use appropriate means of contraception throughout study participation until 28 days after last dose administration 14. Patient, or patient’s legal representative, is able and willing to provide written informed consent and the patient is willing to comply with the study requirements Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Untreated hypo- or hyperthyroidism 2. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed before the first dose of study drug administration 3. Active infection with hepatitis B or hepatitis C (based on serology) 4. Known human immunodeficiency virus infection 5. New York Heart Association (NYHA) classification of >2 6. Known leptomeningeal amyloidosis 7. Other known causes of sensorimotor or autonomic neuropathy (eg, autoimmune disease) 8. Known type I diabetes 9. Type II diabetes mellitus for =5 years from the time of informed consent 10. Vitamin B12 levels below the lower limit of normal 11. Known history of alcohol abuse within the last 2 years from the time of informed consent 12. Received an investigational agent or device within 30 days of anticipated study drug administration or 5 half-lives of the study drug, whichever is longer 13. Currently taking diflunisal, tafamidis, doxycycline, or tauroursodeoxycholic acid; if previously on any of these agents, must have completed a 14-day washout before start of study drug administration in this study 14. Malignancy within the last 2 years from the time of informed consent, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated 15. History of allergic reaction to an oligonucleotide or N-acetylgalactosamine (GalNAc) 16. History of intolerance to subcutaneous (SC) injection 17. Other medical conditions or comorbidities which, in the opinion of the Investigator, would interfere with study compliance or data interpretation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assess the efficacy of revusiran in patients with Transthyretin (TTR) -mediated Familial Amyloidotic Polyneuropathy (FAP) with disease progression post-orthotopic liver transplant (OLT) by evaluating the reduction in serum TTR level compared to baseline;Secondary Objective: • Evaluate the safety and tolerability of revusiran when administered to TTR-mediated FAP patients with disease progression post-OLT • Characterize the pharmacokinetics (PK) of revusiran • Describe the effect of revusiran on neurologic impairment ;Primary end point(s): The primary endpoint is the percent reduction from baseline in serum TTR level at 6 months.;Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of the study are the change from baseline over 18 months for the following: • Serum TTR • Modified (m)NIS+7 • Norfolk Quality of Life-Diabetic Neuropathy questionnaire • PND Score ;Timepoint(s) of evaluation of this end point: 18 months | — |
Countries
Portugal, Spain, Sweden
Contacts
Public ContactClinical Trial Hotline
Alnylam Pharmaceuticals Inc
Outcome results
None listed