Study to learn more about the safety of Fazirsiran and to find out if it can help people with an alpha-1-antitrypsin liver disease with mild liver scarring (fibrosis).

Austria, Belgium, Canada, France, Germany, Italy, Poland, Portugal, Spain, Sweden, Switzerland, United Kingdom, United States (ICTRP)

ICTRP Studien-ID
NCT06165341 (ICTRP)

Offizieller Titel (Genehmigt von der Ethikkommission)
A Randomized, Double-blind, Placebo-Controlled, Phase 3 Study to Evaluate the Safety and Efficacy of Fazirsiran in the Treatment of Alpha-1 Antitrypsin Deficiency–Associated Liver Disease With METAVIR Stage F1 Fibrosis (BASEC)

Wissenschaftlicher Titel
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Safety and Efficacy of Fazirsiran in the Treatment of Alpha-1 Antitrypsin Deficiency-Associated Liver Disease With METAVIR Stage F1 Fibrosis (ICTRP)

Öffentlicher Titel
Study to Learn About the Safety of Fazirsiran and if it Can Help People With Alpha-1 Antitrypsin Liver Disease With Mild Liver Scarring (Fibrosis) (ICTRP)

Untersuchte Krankheit(en)
Alpha1-Antitrypsin Deficiency (ICTRP)

Untersuchte Intervention
Drug: Fazirsiran InjectionDrug: Placebo (ICTRP)

Studientyp
Interventional (ICTRP)

Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator). (ICTRP)

Ein-/Ausschlusskriterien
Inclusion Criteria:

- In the opinion of the investigator, the participant is capable of understanding and
fully complying with the protocol requirements and adhering to the protocol
schedule.

- The participant is able to read, understand, and complete the study questionnaires
electronically per the investigator's judgment.

- The participant signs and dates a written Informed Consent Form (ICF). Any required
privacy authorization should also be signed before the initiation of any study
procedures.

- The participant, of any sex, is aged 18 to 75 years, inclusive.

- The participant must have a diagnosis of the protease inhibitor Z mutation (PiZZ)
genotype AATD. A diagnosis of PiZZ from source-verifiable medical records is
permitted. Otherwise, participants must undergo PiZZ confirmatory testing
(genotyping for PiS and PiZ alleles) at screening. PiMZ or PiSZ genotypes are not
permitted.

- The participant's liver biopsy core samples collected as per protocol requirements.

- The participant has evidence of METAVIR stage F1 liver fibrosis, evaluated by a
centrally read baseline liver biopsy during the screening period or confirmed as
meeting all the entry criteria by central reading from a previous biopsy conducted
within 1 year before the estimated enrollment date using an adequate liver biopsy
and slides as defined in the study laboratory manual.

- The participant has a pulmonary status that meets the protocol requirements.

- It must be confirmed that the participant does not have hepatocellular carcinoma
(HCC).

- Any participant who is taking statins, angiotensin-converting enzyme inhibitors,
angiotensin II receptor blockers, or beta-1 selective adrenergic receptor inhibitors
must have been receiving a stable dose of these medications for at least 8 weeks
before randomization. All attempts are to be made for the participant to continue
the same dose of the medication for the duration of study participation.

- An adult participant must have a body mass index (BMI) between 18 and 39 kilogram
per meter square (kg/m^2), inclusive.

- The participant has a 12-lead electrocardiogram at screening that, in the opinion of
the investigator, has no abnormalities that could compromise the participant's
safety in this study.

- The participant is a nonsmoker.

- If the participant was being treated with any respiratory medications including
inhaled bronchodilators, inhaled anticholinergics, inhaled corticosteroids, or
low-dose systemic corticosteroids (prednisone less than or equal to [<=10]
milligrams per day [mg/d] or its equivalent), the doses of the participant's
medications must have remained unchanged for greater than or equal to (>=) 4 weeks
before screening.

- The participant must have suitable venous access for blood sampling.

- A person of childbearing potential (POCBP) must have a negative serum pregnancy test
at screening and a negative urine pregnancy test on Day 1 before dosing.

- The participant must use appropriate contraception methods (that is, highly
effective methods for female and medically appropriate methods for male study
participants) for the entire duration of the study and for 6 months after the last
dose of study medication. The participant must not donate sperm for at least 6
months after the last dose of study medication.

Exclusion criteria:

- The participant has evidence of >= F2 fibrosis based on liver biopsy during the
screening period.

- The participant has a history of liver decompensating events.

- The participant has a history of varices based on a previous
esophagogastroduodenoscopy.

- The participant has portal vein thrombosis.

- The participant has undergone a prior trans-jugular portosystemic shunt procedure.

- The participant has evidence of other forms of chronic liver diseases.

- The participant has a history of malignancy within the last 5 years, except for
adequately treated basal cell carcinoma, squamous cell skin cancer, superficial
bladder tumors, or in situ cervical cancer. Participants with curatively treated
malignancies who have no evidence of metastatic disease and disease-free interval
greater than (>) 1 year may be enrolled after approval by the medical monitor.

- The participant has an abnormal finding of clinical relevance at the screening
evaluation and before administration of the first dose of study dosing that, in the
opinion of the investigator, could adversely impact participant safety during the
study or adversely impact study results.

- The participant has any laboratory abnormalities at screening and before the first
dose of the study drug that meet protocol parameters.

- The participant is expected to have severe and unavoidable high-level exposure to
inhaled pulmonary toxins during the study such as may occur with occupational
exposure to mineral dusts or metals.

- The participant has a recent lower respiratory tract infection, such as pneumonia,
within the last 6 months before screening. The participant may be screened earlier
based on principal investigator (PI) assessment of clinical recovery and return to
baseline pulmonary function in discussion with the medical monitor.

- The participant has a history of frequent pulmonary exacerbations (>=2 moderate or
severe exacerbations within 52 weeks before screening).

- The participant is experiencing a pulmonary exacerbation at the time of screening
(participant may be rescreened after the clinical resolution of an exacerbation).

- The participant is receiving long-term, around-the-clock oxygen supplementation or
supplemental oxygen with continuous positive airway pressure (CPAP) or bilevel
positive airway pressure for acute respiratory failure. The following conditions are
allowable for the participant to enter screening: short-term use of oxygen
supplementation (example, for the management of acute chronic obstructive pulmonary
disease [COPD] exacerbation) or CPAP for obstructive sleep apnea.

- The participant has human immunodeficiency virus (HIV) infection as shown by the
presence of anti-HIV antibody (seropositive).

- The participant is seropositive for hepatitis B virus (HBV surface antigen positive
and/or HBV core antibody positive without HBV surface antibody at screening) or
hepatitis C virus (HCV) (detectable HCV Ribonucleic Acid [RNA] at screening). Cured
HCV (positive antibody test without detectable HCV RNA for at least 6 months after
treatment) is acceptable.

- The participant has unstable, poorly controlled, or severe hypertension.
Participants may be rescreened once their blood pressure (BP) is successfully
controlled.

- The participant has a history of torsades de pointes, ventricular rhythm
disturbances (example, ventricular tachycardia), heart block (excluding first-degree
block, being PR interval prolongation only), congenital long QT syndrome or new
ST-segment elevation or depression or a new Q wave on ECG. Participants with a
history of atrial arrhythmias should be discussed with the medical monitor.

- The participant has symptomatic (ICTRP)

nicht verfügbar

Primäre und sekundäre Endpunkte
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs);Number of Participants With Clinically Significant Change From Baseline in Pulmonary Function Parameters;Change From Baseline in Whole Lung 15th Percentile Density as Measured by Computed Tomography (CT) Lung Densitometry;Number of Participants With Clinically Significant Changes in Vital Signs;Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Parameters;Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters (ICTRP)

Change From Baseline in Serum Z-AAT Protein Over Time to Week 106;Percent Change From Baseline in Intrahepatic Liver Z-AAT Protein at Week 106;Change From Baseline in Intrahepatic Z-AAT Protein Polymer Burden Assessed by Periodic Acid Schiff Plus Diastase (PAS+D) Staining in Liver Biopsy at Week 106;Number of Participants with No Change or Decrease From Baseline in Intrahepatic Z-AAT Protein Polymer Burden Assessed by PAS+D staining at Week 106;Change From Baseline in Intrahepatic Portal Inflammation Score in Liver Biopsy at Week 106;Number of Participants with No Change or Decrease From Baseline in Intrahepatic Portal Inflammation Score at Week 106;Number of Participants With No Change or Decrease From Baseline in Histologic Fibrosis Score (Meta-analysis of Histological Data in Viral Hepatitis [METAVIR] Staging ) at Week 106;Change From Baseline in Vibration-Controlled Transient Elastography (VCTE)-Derived Liver Stiffness;Change From Baseline in Markers of Liver Injury (ICTRP)

Registrierungsdatum
nicht verfügbar

Einschluss des ersten Teilnehmers
nicht verfügbar

Sekundäre Sponsoren
nicht verfügbar

Weitere Kontakte
Study Director;Takeda Contact, medinfoUS@takeda.com, +1-877-825-3327, Takeda, (ICTRP)

Sekundäre IDs
2023-504198-19-00, TAK-999-3002 (ICTRP)

Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar

Weitere Informationen zur Studie
https://clinicaltrials.gov/study/NCT06165341 (ICTRP)