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

NCT06186492 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: WVE-006-001
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief 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 pharmacokinetics (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.

Conditions

Alpha-1 Antitrypsin Deficiency (AATD)

Outcome Measures

Primary Outcomes (1)

• The Proportion of Participants With Adverse Events

  The number of participants who reported an adverse event (AE) will be summarised.

  Adverse events are collected from the date of consent until up to 85 days after the dose in Period 1 and up to 113 days after the first dose in Period 2.

Secondary Outcomes (6)

• Single Ascending Dose (Period 1) - Area Under the Plasma Concentration Time Curve for WVE-006 From Time of Dosing to the Last Measurable Concentration (AUClast)

  Samples collected at the following timepoints: Day 1 pre-dose, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr & 12 hr post-Day 1 dose, Day 2: 24 hr & 36 hr post-Day 1 dose, Day 3: 48 hr post-Day 1 dose, Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78 & 85.

• Single Ascending Dose - Maximum Concentration of WVE-006 in Plasma (Cmax)

  Samples collected at the following timepoints: Day 1 pre-dose, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr & 12 hr post-Day 1 dose, Day 2: 24 hr & 36 hr post-Day 1 dose, Day 3: 48 hr post-Day 1 dose, Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78 & 85.

• Multiple Ascending Doses - Area Under the Plasma Concentration Time Curve for WVE-006 From Time of Dosing to the Last Measurable Concentration (AUClast) - Day 1

  Samples collected at the following timepoints for Day 1 measurement: Day 1 pre-dose, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr & 24 hr post-dose.

• Multiple Ascending Doses - Maximum Concentration of WVE-006 in Plasma (Cmax) - Day 1

  Samples collected at the following timepoints for Day 1 measurement: Day 1 pre-dose, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr & 24 hr post-dose.

• Multiple Ascending Doses - Area Under the Plasma Concentration Time Curve for WVE-006 From Time of Dosing to the Last Measurable Concentration (AUClast) - Day 29

  Samples collected at the following timepoints for Day 29 measurement: Day 29 pre-dose, 30 mins, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr & 24 hr post-dose.

Study Arms (6)

Single Ascending Dose (SAD): WVE-006 30 milligram (mg) or placebo

EXPERIMENTAL

Drug: WVE-006

SAD: WVE-006 100 mg or placebo

EXPERIMENTAL

Drug: WVE-006

SAD WVE-006 200 mg or placebo

EXPERIMENTAL

Drug: WVE-006

SAD: WVE-006 400 mg or placebo

EXPERIMENTAL

Drug: WVE-006

SAD: WVE-006 600 mg or placebo

EXPERIMENTAL

Drug: WVE-006

Multiple Dose: WVE-006 600 mg Every 2 weeks (Q2W) or placebo

EXPERIMENTAL

Drug: WVE-006

Interventions

WVE-006 DRUG

RNA editing oligonucleotide

Multiple Dose: WVE-006 600 mg Every 2 weeks (Q2W) or placebo; SAD WVE-006 200 mg or placebo; SAD: WVE-006 100 mg or placebo; SAD: WVE-006 400 mg or placebo; SAD: WVE-006 600 mg or placebo; Single Ascending Dose (SAD): WVE-006 30 milligram (mg) or placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

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.
• 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.

Sponsors & Collaborators

• Wave Life Sciences Ltd.: lead

Study Sites (1)

Simbec-Orion Clinical Pharmacology,

Merthyr Tydfil, Wales, CF48 4DR, 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

Results Point of Contact

• Title: Clinical Operations
• Organization: Wave Life Sciences UK Limited

clinicaltrials@wavelifesci.com

+1-855-215-4687

Study Officials

• Cynthia Caracta, MD

  Wave Life Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2023
• First Posted: January 2, 2024
• Study Start: November 14, 2023
• Primary Completion: February 13, 2025
• Study Completion: February 13, 2025
• Last Updated: March 23, 2026
• Results First Posted: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)