A Safety and Tolerability Study of an Investigational Drug, ALN-TTRSC02, in Healthy Subjects

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

The purpose of this study is to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of ALN-TTRSC02 in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Transthyretin-mediated Amyloidosis (ATTR Amyloidosis)
• Intervention / Treatment: Drug: Sterile Normal Saline (0.9% NaCl); Drug: ALN-TTRSC02

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ALN-TTRSC02	Drug: ALN-TTRSC02; Ascending doses of ALN-TTRSC02 by subcutaneous (SC) injection
Placebo Comparator: Sterile normal saline 0.9% for SC administration	Drug: Sterile Normal Saline (0.9% NaCl); Calculated volume to match active comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety of ALN-TTRSC02, evaluated by the proportion of subjects experiencing adverse events (AEs)	Day 1 through to Day 314

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Profile of pharmacokinetics (PK) of ALN-TTRSC02	Cmax	Day 1 through to Day 3
Profile of pharmacokinetics (PK) of ALN-TTRSC02	tmax	Day 1 through to Day 3
Profile of pharmacokinetics (PK) of ALN-TTRSC02	AUC	Day 1 through to Day 3
Profile of pharmacokinetics (PK) of ALN-TTRSC02	t½	Day 1 through to Day 3
Profile of pharmacokinetics (PK) of ALN-TTRSC02	CL/F	Day 1 through to Day 3
Profile of pharmacokinetics (PK) of ALN-TTRSC02	Vss/F	Day 1 through to Day 3
Profile of pharmacokinetics (PK) of ALN-TTRSC02	Vz/F	Day 1 through to Day 3
Profile of pharmacokinetics (PK) of ALN-TTRSC02	fe	Day 1 through to Day 314
Profile of pharmacokinetics (PK) of ALN-TTRSC02	CLR	Day 1 through to Day 314
Effect of ALN-TTRSC02 on serum TTR levels as measured by reduction from baseline in serum TTR		Day 1 through to Day 314
Effect of ALN-TTRSC02 on serum Vitamin A levels as measured by reduction from baseline in serum Vitamin A		Screening through to Day 314

Collaborators and Investigators

• Sponsor: Alnylam Pharmaceuticals
• Investigators: Study Director: John Vest, MD, PhD, Alnylam Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2016
• Primary Completion (Actual): January 12, 2018
• Study Completion (Actual): January 12, 2018

Study Registration Dates

• First Submitted: May 18, 2016
• First Submitted That Met QC Criteria: June 8, 2016
• First Posted (Estimate): June 14, 2016

Study Record Updates

• Last Update Posted (Actual): September 21, 2018
• Last Update Submitted That Met QC Criteria: September 20, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: RNAi therapeutic; Amyloidosis, Hereditary; Amyloidosis, Hereditary, Transthyretin-Related; Familial Amyloidosis; Familial Amyloid Polyneuropathies; Amyloid Neuropathies; TTR-mediated Amyloidosis; Amyloid Neuropathies, Familial
• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis
• Other Study ID Numbers: ALN-TTRSC02-001; 2015-005803-98 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided