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

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

Official Title
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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

Conditions
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Transthyretin-mediated Amyloidosis (ATTR Amyloidosis)

Intervention / Treatment
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* Drug: ALN-TTRSC02
* Drug: Sterile Normal Saline (0.9% NaCl)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TTR-mediated Amyloidosis, Amyloidosis, Hereditary, Amyloid Neuropathies, Familial, Familial Amyloid Polyneuropathies, Amyloid Neuropathies, Amyloidosis, Hereditary, Transthyretin-Related, Familial Amyloidosis, RNAi therapeutic