Clinical trial NCT06405633: A Phase 1b/2a, Open-label Single Ascending Doses and Multiple Ascending Doses Study in Participants with Pi*ZZ AATD
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Alpha-1 Antitrypsin Deficiency
Lead sponsor: Wave Life Sciences Ltd.
Sponsor class: INDUSTRY
First posted: 2024-05-08
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: The proportion of participants with adverse events
timeFrame: Up to 36 Weeks
Secondary outcomes:
measure: Single Ascending Dose - Change from baseline in levels of serum M-AAT protein.
timeFrame: Up to 12 Weeks
measure: Multiple Ascending Dose - Change from baseline in levels of serum M-AAT protein
timeFrame: Up to 24 Weeks
measure: Single Ascending Dose - Area under the plasma concentration time curve for WVE-006 from time of dosing to the last measurable concentration (AUClast)
timeFrame: Up to 12 Weeks
measure: Single Ascending Dose - Maximum concentration of WVE-006 in plasma
timeFrame: Up to 12 Weeks
measure: Multiple Ascending Doses - Area under the plasma concentration time curve for WVE-006 from time of dosing to the last measurable concentration (AUClast)
timeFrame: Up to 24 Weeks
measure: Multiple Ascending Doses - Maximum concentration of WVE-006 in plasma (Cmax)
timeFrame: Up to 24 Weeks
Other outcomes:
Locations:
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital, Melbourne
state: Victoria
city: Halifax
country: Canada
facility: Dalhousie University - Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: Toronto
country: Canada
facility: Inspiration Research Limited
state: Ontario
city: Turku
country: Finland
facility: Turku University Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital, University Hospital Birmingham
Study officials:
affiliation: Wave Life Sciences
name: Cynthia Caracta, MD
role: STUDY_DIRECTOR
References: