A Study of Belcesiran in Patients With A1ATD-Associated Liver Disease (ESTRELLA)

A Study of Belcesiran in Patients With A1ATD-Associated Liver Disease (ESTRELLA)

Brief Summary:
This is a multiple dose, randomized, placebo-controlled, double-blind study of belcesiran to evaluate the safety, tolerability, PK, and PD in adult patients with PiZZ A1ATD-associated liver disease.

The study will be conducted in 2 parallel cohorts. A total of up to 27 participants may be enrolled in a single cohort. The 2 cohorts are differentiated only by the duration of the treatment period, the number of doses administered, and the timing of the end-of-treatment (EOT) liver biopsy. Participants in Cohort 1 will undergo EOT biopsy at 24 weeks, and participants in Cohort 2 will undergo EOT biopsy at 48 weeks.

Detailed Description:
A1ATD-associated liver disease is a progressive Alpha-1 Antitrypsin-Deficiency Associated Liver Disease condition resulting in liver fibrosis, cirrhosis, and hepatocellular carcinoma. The lack of functional A1AT in individuals with the PiZZ genotype, in conjunction with other precipitating factors, can lead to unchecked activity of neutrophil elastases in the alveoli; causing emphysema and chronic obstructive pulmonary disease (COPD). This loss-of-function mechanism can be addressed with intravenous augmentation therapy, which aims to substitute the missing A1AT by infusing alpha-1 proteinase inhibitor (A1PI), purified from pooled human plasma.

While augmentation therapy can address the loss of A1AT in the lung, no treatment exists for the associated liver disease.

Given the severity of the disease, with approximately 10% of affected patients developing liver cirrhosis and a subgroup of those patients in need of liver transplantation, and the lack of an effective treatment that addresses the toxic hepatic "gain-of-function" mechanism, there is an urgent unmet medical need to develop a therapy that can help this particular patient population.


Study Type: Interventional (Clinical Trial)
Estimated Enrollment: 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: Double blind
Primary Purpose: Other
Official Title: A Phase 2a, Randomized, Double-blind, Placebo Controlled, Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of Belcesiran in Patients With PiZZ Alpha-1 Antitrypsin Deficiency
Actual Study Start Date: February 12, 2021
Estimated Primary Completion Date: December 1, 2022
Estimated Study Completion Date: December 1, 2023

Arms:
- Experimental: Experimental: belcesiran
- Placebo Comparator: Placebo

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