A study to look at the efficacy and safety of an investigational drug, revusiran, in the treatment of patients with Transthyretin-Mediated amyloidosis, whose disease has continued to worsen following liver transplantatio

Phase 1

Conditions: Transthyretin (TTR)-mediated Familial Amyloidotic Polyneuropathy (FAP)
MedDRA version: 18.0Level: PTClassification code 10019889Term: Hereditary neuropathic amyloidosisSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Registration Number: EUCTR2015-002603-29-ES

Lead Sponsor: Alnylam Pharmaceuticals, Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 12

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

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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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