Clinical trial NCT02797847: A Safety and Tolerability Study of an Investigational Drug, ALN-TTRSC02, in Healthy Subjects
Official title: A Phase 1, Randomized, Single-Blind, Placebo Controlled, Single-Ascending Dose, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Subcutaneously Administered ALN-TTRSC02 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Transthyretin-mediated Amyloidosis (ATTR Amyloidosis)
Keywords: TTR-mediated Amyloidosis
Amyloidosis, Hereditary
Amyloid Neuropathies, Familial
Familial Amyloid Polyneuropathies
Amyloid Neuropathies
Amyloidosis, Hereditary, Transthyretin-Related
Familial Amyloidosis
RNAi therapeutic
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2016-06-14
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
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 ALN-TTRSC02 in healthy subjects.


Eligibility criteria: Inclusion Criteria:

* Male and female subjects, age 18 to 65 years, inclusive.
* Body mass index (BMI) ≥18.0 kg/m2 and ≤30 kg/m2 assessed at Screening.
* No clinically significant health concerns, as determined by medical history and physical examination, in the opinion of the Investigator.
* Women of child bearing potential must have a negative pregnancy test, cannot be breastfeeding, and must be willing to use contraception, willing and able to comply with the study requirements and to provide written informed consent.
* For Japanese cohorts, subjects of Japanese descent are defined as people carrying a Japanese passport, descendants of 4 Japanese grandparents, and have not been outside Japan for more than 5 years.

Exclusion Criteria:

* Clinically relevant history or presence of respiratory, gastrointestinal, renal, cardiovascular, hepatic, hematological, lymphatic, neurological, psychiatric, musculoskeletal, genitourinary, immunological, and other inflammatory diseases, or dermatological or connective tissue diseases or disorders.
* Active serious mental illness or psychiatric disorder.
* Clinically significant ECG abnormalities. Abnormal for AST/ALT and any other clinical safety laboratory result considered clinically significant.
* Known history of allergic reaction to an oligonucleotide or GalNAc.
* History of intolerance to subcutaneous injection.

Primary outcomes:
measure: Safety of ALN-TTRSC02, evaluated by the proportion of subjects experiencing adverse events (AEs)
timeFrame: Day 1 through to Day 314
Secondary outcomes:
measure: Profile of pharmacokinetics (PK) of ALN-TTRSC02
timeFrame: Day 1 through to Day 3
measure: Profile of pharmacokinetics (PK) of ALN-TTRSC02
timeFrame: Day 1 through to Day 3
measure: Profile of pharmacokinetics (PK) of ALN-TTRSC02
timeFrame: Day 1 through to Day 3
measure: Profile of pharmacokinetics (PK) of ALN-TTRSC02
timeFrame: Day 1 through to Day 3
measure: Profile of pharmacokinetics (PK) of ALN-TTRSC02
timeFrame: Day 1 through to Day 3
measure: Profile of pharmacokinetics (PK) of ALN-TTRSC02
timeFrame: Day 1 through to Day 3
measure: Profile of pharmacokinetics (PK) of ALN-TTRSC02
timeFrame: Day 1 through to Day 3
measure: Profile of pharmacokinetics (PK) of ALN-TTRSC02
timeFrame: Day 1 through to Day 314
measure: Profile of pharmacokinetics (PK) of ALN-TTRSC02
timeFrame: Day 1 through to Day 314
measure: Effect of ALN-TTRSC02 on serum TTR levels as measured by reduction from baseline in serum TTR
timeFrame: Day 1 through to Day 314
measure: Effect of ALN-TTRSC02 on serum Vitamin A levels as measured by reduction from baseline in serum Vitamin A
timeFrame: Screening through to Day 314
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
affiliation: Alnylam Pharmaceuticals
name: John Vest, MD, PhD
role: STUDY_DIRECTOR
References: