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 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: Recruiting
• Conditions: Alpha-1 Antitrypsin Deficiency
• Intervention / Treatment: Drug: WVE-006

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Operations; Phone Number: 855-215-4687; Email: Clinicaltrials@wavelifesci.com

Study Locations

• United Kingdom
  • Wales
    • Merthyr Tydfil, Wales, United Kingdom, CF48 4DR
      • Recruiting
      • Simbec-Orion Clinical Pharmacology,
      • Contact: Annelize Koch, MBChB; Email: annelize.koch@simbecorion.com

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

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental WVE-006 (Dose A) or placebo	Drug: WVE-006; RNA editing oligonucleotide
Experimental: Experimental WVE-006 (Dose B) or placebo	Drug: WVE-006; RNA editing oligonucleotide
Experimental: Experimental WVE-006 (Dose C) or placebo	Drug: WVE-006; RNA editing oligonucleotide
Experimental: Experimental WVE-006 (Dose D) or placebo	Drug: WVE-006; RNA editing oligonucleotide
Experimental: Experimental WVE-006 (Dose E) or placebo	Drug: WVE-006; RNA editing oligonucleotide
Experimental: Experimental WVE-006 (Dose F) or placebo	Drug: WVE-006; RNA editing oligonucleotide
Experimental: Experimental WVE-006 (Dose G) or placebo	Drug: WVE-006; RNA editing oligonucleotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The proportion of participants with adverse events	Day 1 through Day 85 after last dose.

Secondary Outcome Measures

Outcome Measure	Time Frame
Single Ascending Dose - Area under the plasma concentration time curve for WVE-006 from time of dosing to the last measurable concentration (AUClast)	Day 0 through Day 84 postdose
Single Ascending Dose - Maximum concentration of WVE-006 in plasma (Cmax)	Day 0 through Day 84 postdose
Multiple Ascending Doses - Area under the plasma concentration time curve for WVE-006 from time of dosing to the last measurable concentration (AUClast)	Day 0-14 after the first and Day 0-84 days after the last dose, respectively
Multiple Ascending Doses - Maximum concentration of WVE-006 in plasma (Cmax)	Day 0-14 after the first and Day 0-84 days after the last dose, respectively

Collaborators and Investigators

• Sponsor: Wave Life Sciences Ltd.
• Investigators: Study Director: Mike Tillinger, MD, Wave Life Sciences

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: November 9, 2023
• First Submitted That Met QC Criteria: December 15, 2023
• First Posted (Estimated): January 1, 2024

Study Record Updates

• Last Update Posted (Estimated): January 1, 2024
• Last Update Submitted That Met QC Criteria: December 15, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Liver Diseases; Genetic Diseases, Inborn; Subcutaneous Emphysema; Emphysema; 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