A Phase 1b/2a, Open-label Single Ascending Doses and Multiple Ascending Doses Study in Participants With Pi*ZZ AATD (RestorAATion-2)

A Phase 1b/2a Open-label Single Ascending Doses (SAD) and Multiple Ascending Doses (MAD) Research Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Participants With AATD Pi*ZZ on WVE-006 (RestorAATion-2)

The purpose of this open-label study is to assess the safety, tolerability, pharmacodynamics, and pharmacokinetics of WVE-006 in participants with alpha-1 antitrypsin deficiency (AATD) following Period 1 single ascending dose (SAD) and Period 2 multiple ascending doses (MAD), respectively.

Study Overview

• Status: Active, not recruiting
• Conditions: Alpha-1 Antitrypsin Deficiency
• Intervention / Treatment: Drug: WVE-006

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St. Vincent's Hospital, Melbourne
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Dalhousie University - Queen Elizabeth II Health Sciences Centre
  • Ontario
    • Toronto, Ontario, Canada, M5T 3A9
      • Inspiration Research Limited
• Finland
  • Turku, Finland, 20520
    • Turku University Hospital
• Germany
  • Aachen, Germany, 52074
    • Universitaetsklinikum Aachen, AoeR
• New Zealand
  • Hamilton, New Zealand, 3204
    • Waikato Hospital
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • Queen Elizabeth Hospital, University Hospital Birmingham
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University - Addenbrooke's Hospital
  • London, United Kingdom, SW8 3RN
    • Royal Free London NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Healthy as determined by the Investigator, based on a medical evaluation, or has mild to moderate AATD-induced lung disease (FEV1 ≥50%) and/or stable mild AATD-induced liver disease (≤F2 (≤10 kPa) on FibroScan.
• Genetic testing confirming Pi*ZZ.
• 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.
  • Any recent or planned major surgery during the study.
  • Participant has any medical condition or social circumstance that, in the opinion of the Investigator, would make the participant unsuitable for participation in the study or for dosing on Day 1, or could interfere with the assessments of safety, pharmacodynamics, or pharmacokinetics, or completion of the study.
  • Participant currently on AAT augmentation therapy, planned to be on augmentation therapy anytime during the study, or has been on augmentation therapy within 30 days prior to Screening Visit.
  • 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: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: WVE-006 (Dose 1)	Drug: WVE-006; RNA editing oligonucleotide
Experimental: WVE-006 (Dose 2)	Drug: WVE-006; RNA editing oligonucleotide
Experimental: WVE-006 (Dose 3)	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	Up to 36 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Single Ascending Dose - Change from baseline in levels of serum M-AAT protein.	Up to 12 Weeks
Multiple Ascending Dose - Change from baseline in levels of serum M-AAT protein	Up to 24 Weeks
Single Ascending Dose - Area under the plasma concentration time curve for WVE-006 from time of dosing to the last measurable concentration (AUClast)	Up to 12 Weeks
Single Ascending Dose - Maximum concentration of WVE-006 in plasma	Up to 12 Weeks
Multiple Ascending Doses - Area under the plasma concentration time curve for WVE-006 from time of dosing to the last measurable concentration (AUClast)	Up to 24 Weeks
Multiple Ascending Doses - Maximum concentration of WVE-006 in plasma (Cmax)	Up to 24 Weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: May 3, 2024
• First Submitted That Met QC Criteria: May 3, 2024
• First Posted (Actual): May 8, 2024

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 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-006-002

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