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

Alpha-1 Antitrypsin Deficiency Clinical Trial

— RestorAATion-2  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06405633
• Other study ID #: WVE-006-002
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 2024
• Est. completion date: July 2025

Study information

• Verified date: May 2024
• Source: Wave Life Sciences Ltd.
• Contact: Clinical Operations
• Phone: 855-215-4687
• Email: Clinicaltrials[@]wavelifesci.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alpha 1-Antitrypsin Deficiency
• Alpha-1 Antitrypsin Deficiency

Intervention

Drug:
• WVE-006
RNA editing oligonucelotide

Locations

Country	Name	City	State
Canada	Inspiration Research Limited	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Wave Life Sciences Ltd.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of participants with adverse events		Up to 36 Weeks
Secondary	Single Ascending Dose - Change from baseline in levels of serum M-AAT protein.		Up to 12 Weeks
Secondary	Multiple Ascending Dose - Change from baseline in levels of serum M-AAT protein		Up to 24 Weeks
Secondary	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
Secondary	Single Ascending Dose - Maximum concentration of WVE-006 in plasma		Up to 12 Weeks
Secondary	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
Secondary	Multiple Ascending Doses - Maximum concentration of WVE-006 in plasma (Cmax)		Up to 24 Weeks