Clinical trial NCT01148953: Trial to Evaluate Safety and Tolerability of ALN-TTR01 in Transthyretin (TTR) Amyloidosis
Official title: A Phase 1, Randomized, Single-Blind, Placebo-Controlled, Dose Escalation Trial to Evaluate the Safety and Tolerability of a Single Dose of Intravenous ALN-TTR01 in Patients With TTR Amyloidosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Transthyretin Mediated Amyloidosis (ATTR)
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2010-06-23
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of a single dose of ALN-TTR01 in patients with transthyretin (TTR) mediated amyloidosis (ATTR).


Eligibility criteria: Inclusion Criteria:

* Diagnosis of TTR amyloidosis
* Adequate blood counts, liver and renal function
* Women of child-bearing potential must have a negative pregnancy test, cannot be breast feeding, and must use an adequate method of birth control
* Males agree to use appropriate contraception
* Willing and able to comply with protocol-required visit schedule and visit requirements and provide written informed consent.

Exclusion Criteria:

* Known human immunodeficiency virus (HIV) positive status
* Receiving antibiotics for bacterial infection within 7 days of screening
* Known or suspected systemic viral, parasitic or fungal infection
* Receiving an investigational agent within 30 days prior to study drug administration
* Poor cardiac function
* Considered unfit for the study by the Principal Investigator
* Known sensitivity to oligonucleotides
* Employee or family member of the sponsor or the clinical study site personnel.

Primary outcomes:
measure: The proportion of patients experiencing adverse events (AEs), serious adverse events (SAEs), and study drug discontinuation.
timeFrame: Up to 28 Days
Secondary outcomes:
measure: Pharmacokinetics (PK) of ALN-TTR01 (Cmax, tmax, t1/2, AUC0-last, CL)
timeFrame: Up to 70 days
measure: Effect of ALN-TTR01 on Circulating TTR Levels (Determination of % Lowering of TTR to Pretreatment/Baseline TTR Level)
timeFrame: up to 70 days
Other outcomes:
Locations:
city: Le Kremlin Bicêtre
country: France
facility: Clinical Site
city: Porto
country: Portugal
facility: Clinical Site
city: Umeå
country: Sweden
facility: Clinical Site
city: London
country: United Kingdom
facility: Clinical Site
Study officials:
affiliation: Alnylam Pharmaceuticals Inc
name: Jared Gollob, MD
role: STUDY_DIRECTOR
References:
citation: Coelho T, Adams D, Silva A, Lozeron P, Hawkins PN, Mant T, Perez J, Chiesa J, Warrington S, Tranter E, Munisamy M, Falzone R, Harrop J, Cehelsky J, Bettencourt BR, Geissler M, Butler JS, Sehgal A, Meyers RE, Chen Q, Borland T, Hutabarat RM, Clausen VA, Alvarez R, Fitzgerald K, Gamba-Vitalo C, Nochur SV, Vaishnaw AK, Sah DW, Gollob JA, Suhr OB. Safety and efficacy of RNAi therapy for transthyretin amyloidosis. N Engl J Med. 2013 Aug 29;369(9):819-29. doi: 10.1056/NEJMoa1208760.