A Phase 1 Research Study to Evaluate Safety, Tolerability, and Pharmacokinetics of WVE-006 in Healthy Participants With Wild-type AAT Expression (RestorAATion-1)

Wave Life Sciences USA, Inc.47 enrolled

Overview

This study is the first study in the RestorAATion clinical program. The purpose of this first-in human (FIH), double-blind, randomized, placebo-controlled, single ascending dose (SAD) and multiple-dose Phase 1 study is to assess the safety, tolerability, and pharmacokinetics (PK) of WVE-006 compared to placebo in healthy participants following a single dose (Period 1) and multiple doses (Period 2) of WVE-006. This information will be used to determine doses and regimes that have the potential to be pharmacologically active in patients with Alpha-1 antitrypsin deficiency in the RestorAATion 2 study, and the maximum safe and tolerable dose that may be given to these patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Alpha-1 Antitrypsin Deficiency (AATD)

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy as determined by the Investigator, based on a medical evaluation. * Genetic testing confirming PI\*MM. * Participant has been a non-smoker for at least 1 year prior to screening. Exclusion Criteria: * Participant has a history of multiple drug allergies or of allergic reaction to an oligonucleotide or to N-acetylgalactosamine (GalNAc). * Participant has a history of intolerance or any medical condition that might interfere with subcutaneous injections. * Any ongoing or recent infections. * Any recent or planned vaccinations during the study. * Participant has a history of regular alcohol consumption exceeding 14 standard drinks/week. * Unwilling to abstain from alcohol for 48 hours prior to dosing at each of the dosing visits. * Participant has a history of caffeine consumption exceeding 8 cups of coffee/day. * Use of prescription or non-prescription medications, including vitamin, dietary, and herbal supplements (including St John's Wort) within 7 days prior to the first dose of study treatment unless, in the opinion of the Investigator and Sponsor, the medication will not interfere with interpretation of study assessments. Contraception and hormone replacement therapy (HRT) are permitted. If needed, over-the-counter (OTC) medications such as paracetamol/acetaminophen may be used acutely. * Any recent or planned major surgery during the study. * Donation of blood or blood products in excess of 500 mL within 12 weeks prior to Screening Visit and/or unwilling to refrain from blood donation for the duration of the study. * Participant has received an investigational agent within 3 months of the Screening Visit.

Outcomes

Primary Outcomes

The Proportion of Participants With Adverse Events

The number of participants who reported an adverse event (AE) will be summarised.

Time frame: Adverse events are collected from the date of consent until up to 85 days after the dose in Period 1 and up to 113 days after the first dose in Period 2.

Secondary Outcomes

Single Ascending Dose (Period 1) - Area Under the Plasma Concentration Time Curve for WVE-006 From Time of Dosing to the Last Measurable Concentration (AUClast)

Plasma samples were obtained in order to evaluate defined plasma pharmacokinetic parameters for WVE-006. This endpoint will report the summary of derived pharmacokinetic parameters for the Area under the plasma concentration time curve for WVE-006 from time of dosing to the last measurable concentration (AUClast) of WVE-006 in plasma for participants in Period 1 of the study.

Time frame: Samples collected at the following timepoints: Day 1 pre-dose, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr & 12 hr post-Day 1 dose, Day 2: 24 hr & 36 hr post-Day 1 dose, Day 3: 48 hr post-Day 1 dose, Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78 & 85.

Single Ascending Dose - Maximum Concentration of WVE-006 in Plasma (Cmax)

Plasma samples were obtained in order to evaluate defined plasma pharmacokinetic parameters for WVE-006. This endpoint will report the summary of derived pharmacokinetic parameters for the Maximum concentration of WVE-006 in plasma (Cmax) of WVE-006 in plasma for participants in Period 1 of the study.

Multiple Ascending Doses - Area Under the Plasma Concentration Time Curve for WVE-006 From Time of Dosing to the Last Measurable Concentration (AUClast) - Day 1

Time frame: Samples collected at the following timepoints for Day 1 measurement: Day 1 pre-dose, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr & 24 hr post-dose.

Multiple Ascending Doses - Maximum Concentration of WVE-006 in Plasma (Cmax) - Day 1

Plasma samples were obtained in order to evaluate defined plasma pharmacokinetic parameters for WVE-006. This endpoint will report the summary of derived pharmacokinetic parameters for the Maximum concentration of WVE-006 in plasma (Cmax) of WVE-006 in plasma for participants in Period 2 of the study.