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

Alpha-1 Antitrypsin Deficiency Clinical Trial

— RestorAATion-1  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06186492
• Other study ID #: WVE-006-001
• Status: Recruiting
• Phase: Phase 1
• Start date: November 14, 2023
• Est. completion date: December 2024

Study information

• Verified date: December 2023
• 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 56
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• WVE-006
RNA editing oligonucleotide

Locations

Country	Name	City	State
United Kingdom	Simbec-Orion Clinical Pharmacology,	Merthyr Tydfil	Wales

Sponsors (1)

Lead Sponsor	Collaborator
Wave Life Sciences Ltd.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of participants with adverse events		Day 1 through Day 85 after last dose.
Secondary	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
Secondary	Single Ascending Dose - Maximum concentration of WVE-006 in plasma (Cmax)		Day 0 through Day 84 postdose
Secondary	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
Secondary	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