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A Phase 1/2, Open‑Label, Multi‑Center, Dose Escalation, Dose Expansion, and Single Repeat Dose Study of TSRA‑196 in Adults With the PiZZ Genotype Who Have Lung and/or Liver Disease Associated With Severe Alpha‑1 Antitrypsin Deficiency
EU CTIS ID: 2025-523497-16-00
What this study is testing
Part 1: To evaluate the safety and tolerability of a single dose of TSRA-196 in adults with AATD Part 2: To evaluate the efficacy of a single dose of TSRA-196 in adults with AATD Part 3: To evaluate the efficacy of a second dose of TSRA-196 in adult participants with AATD
- Phase I and Phase II (Integrated)- First administration to humans
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Males or females who are 18 to 70 years of age, inclusive, at the time of signing the informed consent
- Part 1A and 2A (AATD lung disease with no or minimal liver fibrosis) • Clinically significant lung disease at baseline that is not more severe than specified in the exclusion criteria • No or minimal liver fibrosis determined by liver biopsy or non-invasive assessment at baseline
- Part 1B and 2B (AATD liver disease with significant or severe liver fibrosis, with or without AATD lung disease) • Moderate-to-severe liver fibrosis determined by liver biopsy at baseline
- 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
You likely can't join if
- Presence of genetic variation in the region around the PiZ variant that may disrupt the function of TSRA-196, determined by screening genotyping.
- 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.
- Unstable AATD-related COPD, as determined by the investigator, or severe bronchiectasis
- Lung volume reduction surgery within 1 year before screening or plan to receive lung volume reduction surgery during the study period (between Screening and the Month 12 EOS visit).
- Documented chronic need for positive airway pressure therapy beyond nocturnal use
See the full eligibility criteria
Who can join
- Males or females who are 18 to 70 years of age, inclusive, at the time of signing the informed consent
- Part 1A and 2A (AATD lung disease with no or minimal liver fibrosis) • Clinically significant lung disease at baseline that is not more severe than specified in the exclusion criteria • No or minimal liver fibrosis determined by liver biopsy or non-invasive assessment at baseline
- Part 1B and 2B (AATD liver disease with significant or severe liver fibrosis, with or without AATD lung disease) • Moderate-to-severe liver fibrosis determined by liver biopsy at baseline
- 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
- Nonsmoker for at least 6 months before screening and must remain nonsmoking for the entire study duration
- Agrees to not consume alcohol for 14 days before TSRA-196 administration and for 30 days after TSRA-196 administration and understands that they should not consume significant amounts of alcohol consumption for the entire study duration.
- Total bilirubin value at screening with or without Gilbert’s syndrome as defined in the protocol.
- Laboratory, hematology values as defined in the protocol
- Either AAT treatment-naïve or washed out of all investigational or approved treatments that modify AAT levels
What rules you out
- Presence of genetic variation in the region around the PiZ variant that may disrupt the function of TSRA-196, determined by screening genotyping.
- 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.
- Unstable AATD-related COPD, as determined by the investigator, or severe bronchiectasis
- Lung volume reduction surgery within 1 year before screening or plan to receive lung volume reduction surgery during the study period (between Screening and the Month 12 EOS visit).
- Documented chronic need for positive airway pressure therapy beyond nocturnal use
- Has received an organ transplant or is on a waiting list for an organ transplant.
- Dependent on continuous supplementary oxygen
- Immunization within 30 days before dosing for attenuated live vaccines and 14 days before dosing for all other vaccines.
- Prior treatment with gene therapy using viral vectors or intended to permanently change the patient’s DNA. Prior treatment with RNA therapeutics is acceptable.
- Seropositive for HIV (HIV-1 or HIV-2), active hepatitis B (HBsAg or HBcAb positive with detectable HBV DNA), or hepatitis C infection (Parts 1A/2A: HCV RNA positive; Parts 1B/2B: HCV RNA and/or antibody positive)
- History of thromboembolic disease, myocardial infarction, or stroke within 6 months of screening
- Uncontrolled hypertension as defined in the protocol
- History of LNP-related reaction classified as CTCAE Grade 3 or higher
- History of active malignancy within 5 years before screening, except basal cell carcinoma of the skin, curatively resected squamous cell carcinoma of the skin, cervical carcinoma in situ curatively treated or low-grade prostate adenocarcinoma for which appropriate management is observation alone.
- Presence of a null or projected loss-of-function variant in the SERPINA1 gene determined by screening genotyping.
- History of liver disease unrelated to AATD
- History of or clinical signs of cirrhosis, e.g., varices or ascites.
The study team makes the final eligibility decision.
Where it's taking place
- United States
- Australia
- United Kingdom
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United States; Australia; United Kingdom. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.