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Completed

NCT Number: NCT06186492

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

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.

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Key information

Conditions

Alpha-1 Antitrypsin Deficiency (AATD) Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Emphysema Genetic Diseases, Inborn Liver Diseases Lung Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Respiratory Tract Diseases Subcutaneous Emphysema alpha 1-Antitrypsin Deficiency

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Simbec-Orion Clinical Pharmacology,

Merthyr Tydfil, Wales, CF48 4DR, United Kingdom

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

WVE-006

Drug

RNA editing oligonucleotide

Primary outcomes

  1. The Proportion of Participants With Adverse Events

    Time frame: 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.

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

Secondary outcomes

  1. 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)

    Time frame: 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.

    Plasma samples were obtained in order to evaluate defined plasma pharmacokinetic parameters for WVE-006. This endpoint will report the summary of derived pharmacokinetic parameters for the Area under the plasma concentration time curve for WVE-006 from time of dosing to the last measurable concentration (AUClast) of WVE-006 in plasma for participants in Period 1 of the study.

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

    Time frame: 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.

    Plasma samples were obtained in order to evaluate defined plasma pharmacokinetic parameters for WVE-006. This endpoint will report the summary of derived pharmacokinetic parameters for the Maximum concentration of WVE-006 in plasma (Cmax) of WVE-006 in plasma for participants in Period 1 of the study.

  3. 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

    Time frame: 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.

    Plasma samples were obtained in order to evaluate defined plasma pharmacokinetic parameters for WVE-006. This endpoint will report the summary of derived pharmacokinetic parameters for the Area under the plasma concentration time curve for WVE-006 from time of dosing to the last measurable concentration (AUClast) of WVE-006 in plasma for participants in Period 2 of the study.

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

    Time frame: 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.

    Plasma samples were obtained in order to evaluate defined plasma pharmacokinetic parameters for WVE-006. This endpoint will report the summary of derived pharmacokinetic parameters for the Maximum concentration of WVE-006 in plasma (Cmax) of WVE-006 in plasma for participants in Period 2 of the study.

  5. 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

    Time frame: 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.

    Plasma samples were obtained in order to evaluate defined plasma pharmacokinetic parameters for WVE-006. This endpoint will report the summary of derived pharmacokinetic parameters for the Area under the plasma concentration time curve for WVE-006 from time of dosing to the last measurable concentration (AUClast) of WVE-006 in plasma for participants in Period 2 of the study.

  6. Multiple Ascending Doses - Maximum Concentration of WVE-006 in Plasma (Cmax) - Day 29

    Time frame: 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.

    Plasma samples were obtained in order to evaluate defined plasma pharmacokinetic parameters for WVE-006. This endpoint will report the summary of derived pharmacokinetic parameters for the Maximum concentration of WVE-006 in plasma (Cmax) of WVE-006 in plasma for participants in Period 2 of the study.

Sponsors and collaborators

Lead sponsor

Wave Life Sciences USA, Inc.

Industry

Registry information

Official study 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

Acronym: RestorAATion-1

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Jan 2, 2024
Registry last updated
Mar 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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