A Study of TSRA-196 in Adults With PiZZ Alpha-1 Antitrypsin Deficiency (AATD)

ConditionAlpha-1 Antitrypsin Deficiency (AATD)

Trial statusRecruiting

Trial phasePhase 1, Phase 2

Trial typeInterventional

Biological sexAll

Age18-70

SponsorTessera Therapeutics, Inc.

About this trial

This is a Phase 1/2, open-label, multi-center, dose escalation (Part 1), dose expansion (Part 2), and single repeat dose (Part 3) study to evaluate the safety, tolerability, efficacy, and PK/PD parameters of TSRA-196 in adults with the PiZZ genotype who have lung and/or liver disease associated with severe alpha-1 antitrypsin deficiency (AATD)

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Males or females who are 18 to 70 years of age, inclusive, at the time of signing the informed consent

Body mass index of 18 to 37 kg/m2, inclusive

Confirmed diagnosis of AATD and PiZZ genotype

At least one previous measure of blood total AAT level <11 µmol/L

Disqualifiers

Presence of genetic variation in SERPINA1 gene that may disrupt the function of TSRA-196, determined by screening genotyping

History of liver disease unrelated to AATD, or history of or clinical signs of cirrhosis

Significant lung disease not attributable to manifestations of AATD, as determined by the investigator

History of one or more hospitalizations due to severe exacerbation of underlying lung disease during the year before screening or received IV antibiotics for treatment of a pulmonary infection within 6 months before screening

Trial design

Design model

Single group

Treatments tested in this trial

TSRA-196
Drug
TSRA-196 is an in-vivo genome editing product formulated in lipid nanoparticles (LNPs) for the treatment of patients with alpha-1 antitrypsin deficiency (AATD), via intravenous (IV) infusion

Treatment groups

72 Participants

are divided into 1 treatment group

Group A: TSRA-196 Drug ProductExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

Part 1 (Dose Escalation): Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

Time frame

1 Year

Part 2 (Dose Expansion): Proportion of participants who have serum levels of total alpha-1 antitrypsin (AAT) greater than or equal to Lower Limit of Normal (LLN) after TSRA-196 treatment

Time frame

1 Year

Part 2 (Dose Expansion): Change in functional AAT concentrations (determined using an elastase inhibition assay) from baseline to end of study

Time frame

1 Year

Part 3 (Single Repeated Dose): Proportion of participants who have serum levels of total alpha-1 antitrypsin (AAT) greater than or equal to Lower Limit of Normal (LLN) after a second dose of TSRA-196

Time frame

1 Year

Secondary outcomes

Part 1 (Dose Escalation): Proportion of participants who have serum levels of total AAT greater than or equal to LLN after TSRA-196 treatment

Time frame

1 Year

Part 2 (Dose Expansion): Incidence of TEAEs and SAEs

Time frame

1 Year

Part 1 (Dose Escalation) and Part 2 (Dose Expansion): Proportion of participants who have serum levels of total AAT greater than or equal to 11 μM after TSRA-196 treatment

Time frame

1 Year

Part 1 (Dose Escalation) and Part 2 (Dose Expansion): Change in serum levels of total AAT from baseline over time

Time frame

1 Year