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

A Phase 1, Randomized, Double-blind, Placebo-controlled, Safety, Tolerability, and Pharmacokinetic Study of Single Ascending Doses and Multiple Doses of WVE-006 in Healthy Participants

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 Overview

• Status: Completed
• Conditions: Alpha-1 Antitrypsin Deficiency (AATD)
• Intervention / Treatment: Drug: WVE-006

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Wales
    • Merthyr Tydfil, Wales, United Kingdom, CF48 4DR
      • Simbec-Orion Clinical Pharmacology,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Ascending Dose (SAD): WVE-006 30 milligram (mg) or placebo	Drug: WVE-006; RNA editing oligonucleotide
Experimental: SAD: WVE-006 100 mg or placebo	Drug: WVE-006; RNA editing oligonucleotide
Experimental: SAD WVE-006 200 mg or placebo	Drug: WVE-006; RNA editing oligonucleotide
Experimental: SAD: WVE-006 400 mg or placebo	Drug: WVE-006; RNA editing oligonucleotide
Experimental: SAD: WVE-006 600 mg or placebo	Drug: WVE-006; RNA editing oligonucleotide
Experimental: Multiple Dose: WVE-006 600 mg Every 2 weeks (Q2W) or placebo	Drug: WVE-006; RNA editing oligonucleotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Proportion of Participants With Adverse Events	The number of participants who reported an adverse event (AE) will be summarised.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.
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	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 2 of the study.	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.	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 - Area Under the Plasma Concentration Time Curve for WVE-006 From Time of Dosing to the Last Measurable Concentration (AUClast) - Day 29	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 2 of the study.	Samples collected at the following timepoints for Day 29 measurement: Day 29 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 29	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.	Samples collected at the following timepoints for Day 29 measurement: Day 29 pre-dose, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr & 24 hr post-dose.

Collaborators and Investigators

• Sponsor: Wave Life Sciences Ltd.
• Investigators: Study Director: Cynthia Caracta, MD, Wave Life Sciences

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2023
• Primary Completion (Actual): February 13, 2025
• Study Completion (Actual): February 13, 2025

Study Registration Dates

• First Submitted: November 9, 2023
• First Submitted That Met QC Criteria: December 15, 2023
• First Posted (Actual): January 2, 2024

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Liver Diseases; Subcutaneous Emphysema; Emphysema; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; alpha 1-Antitrypsin Deficiency
• Other Study ID Numbers: WVE-006-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes