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

NCT06405633 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: WVE-006-002
• Study Type: interventional
• Target: 24
• Locations: 6 countries
• Sites: 9

Brief Summary

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.

Conditions

Alpha-1 Antitrypsin Deficiency

Outcome Measures

Primary Outcomes (1)

• The proportion of participants with adverse events

  Up to 36 Weeks

Secondary Outcomes (6)

• 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

Study Arms (3)

WVE-006 (Dose 1)

EXPERIMENTAL

Drug: WVE-006

WVE-006 (Dose 2)

EXPERIMENTAL

Drug: WVE-006

WVE-006 (Dose 3)

EXPERIMENTAL

Drug: WVE-006

Interventions

WVE-006 DRUG

RNA editing oligonucleotide

WVE-006 (Dose 1); WVE-006 (Dose 2); WVE-006 (Dose 3)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Wave Life Sciences Ltd.: lead

Study Sites (9)

St. Vincent's Hospital, Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Dalhousie University - Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Inspiration Research Limited

Toronto, Ontario, M5T 3A9, Canada

Location

Turku University Hospital

Turku, 20520, Finland

Location

Universitaetsklinikum Aachen, AoeR

Aachen, 52074, Germany

Location

Waikato Hospital

Hamilton, 3204, New Zealand

Location

Queen Elizabeth Hospital, University Hospital Birmingham

Birmingham, B15 2GW, United Kingdom

Location

Cambridge University - Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, SW8 3RN, United Kingdom

Location

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Medical Director, MD

  Wave Life Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2024
• First Posted: May 8, 2024
• Study Start: July 19, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); DE (1); NZ (1); GB (3); CA (2); FI (1)