Alpha-1 Antitrypsin Deficiency (AATD)Early Phase 1AATDNCT07193615
Study of YOLT-202 in the Treatment of Alpha-1 Antitrypsin Deficiency (AATD)
A Early Phase 1 study testing YOLT-202 in people with Alpha-1 Antitrypsin Deficiency (AATD), run by RenJi Hospital at 1 site in China.
Trial summary
This is a single-arm, open-label, single-dose, dose-escalation exploratory study to evaluate the safety and tolerability of a single dose of YOLT-202 in patients with AATD and determine the optimal biologically active dose (OBD) of YOLT-202. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Alpha-1 Antitrypsin Deficiency (AATD)
- What is being tested?
- YOLT-202
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteChina
- Study dates
- 18 Jun 2025to Mar 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female (inclusive) aged ≥ 18 and ≤ 70 years old at the time of signing informed consent.
- Diagnosed with AATD and genetically confirmed as homozygous PiZZ mutation.
- Blood total AAT level < 11 μM or equivalent protein in mg/dL.
- Patients receiving augmentation therapy must be willing to discontinue it at least 6 weeks prior to signing the informed consent form (ICF) and throughout the study period, unless clinically indicated.
Who cannot join
- Body mass index (BMI) > 35 kg/m2.
- Patients who have undergone lung or liver transplantation, are on the waiting list for lung or liver transplantation, or have had lung volume reduction surgery (LVRS).
- Clinical evidence of severe bronchiectasis, as judged by the investigator (e.g., excessive sputum production or recurrent infections requiring antibiotics [> 4 times per year]).
- FEV1 ≤ 30% of predicted value after bronchodilator use at screening
- Liver disease with any of the following:
- Measured liver stiffness (FibroScan) ≥ 10 kilopascals (kPa).
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- Known history of hepatic cirrhosis or associated complications (e.g., varices, ascites, hepatic encephalopathy).
- ≥ F2 hepatic fibrosis in patients with prior liver biopsy.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 times the upper limit of normal (ULN).
- Total bilirubin > ULN; or > 2 times the ULN if Gilbert's syndrome is documented.
- International normalized ratio (INR) ≥ 1.2 at screening. If deemed appropriate by the investigator and/or the prescribing physician, anticoagulants may be discontinued for a washout period or reversed with vitamin K. If necessary, a repeat INR < 1.2 is acceptable.
- Hepatitis B surface antigen (HBsAg) positive.
- Hepatitis C virus (HCV) antibody positive. If HCV antibody is positive, HCV RNA PCR must be negative.
- Allergy to the drugs contained in lipid nanoparticles (LNP) or LNP-mRNA vaccines, or previous history of adverse reactions to LNP-based drugs;
- Smoking more than 5 cigarettes per day or consuming the equivalent amount of nicotine or nicotine replacement products within the past 6 months before screening.
- History of alcohol abuse within the past 6 months before screening (drinking more than 14 units of alcohol per week [1 unit ≈ 360 mL of beer or 45 mL of 40% alcohol or 150 mL of wine]); or positive alcohol breath test at the time of screening or admission.
- Patients with poorly controlled hypertension by conventional treatments (systolic blood pressure [SBP] ≥ 180 mmHg and/or diastolic blood pressure [DBP] ≥ 110 mmHg).
- Patients with poorly controlled diabetes (hemoglobin A1c ≥ 9%).
- Presence of New York Heart Association (NYHA) class III-IV heart failure, left ventricular ejection fraction < 50%, or prolonged QTc interval (female > 470 ms, male > 450 ms) at the time of screening.
- Myocardial infarction, unstable angina pectoris, percutaneous coronary intervention, coronary artery bypass grafting, severe deep vein thrombosis or pulmonary embolism within 3 months before screening; poorly controlled severe arrhythmias within the past 3 months before screening, such as poorly controlled recurrent and highly symptomatic ventricular tachycardia, rapid ventricular response atrial fibrillation, or supraventricular tachycardia; or planned cardiac surgery or cardiac revascularization during the main study period.
- Cerebrovascular accidents within 6 months before screening;
- Known or suspected systemic viral, parasitic, or fungal infections, or active infections requiring expected antibiotic therapy within 14 days after screening.
- Human immunodeficiency virus (HIV) antibody positive at screening.
- Anticoagulant therapy within 14 days before enrollment (such as warfarin, dabigatran, apixaban).
- Patients with bleeding tendency or history of coagulation disorders (such as liver cirrhosis, malignant hematological diseases, antiphospholipid antibody syndrome);
- Expected survival time less than 2 years.
- History of malignant tumors within the past 5 years (excluding cured skin basal cell carcinoma, skin squamous cell carcinoma, cervical carcinoma in situ, low-grade prostate carcinoma in situ, and cured thyroid basal cell carcinoma).
- History of drug abuse within the past 3 years.
- Pregnant or lactating women.
- Patients with other diseases in the blood system, digestive system, central nervous system, or endocrine system that the investigator believes will interfere with evaluation or limit participation in the trial.
- Inability or unwillingness to cooperate or comply with pretreatment medication requirements or study procedures.
- Any other condition deemed unsuitable for the clinical trial participation by the investigator.
Trial locations and contacts
1 site in 1 country.
China1 site
Ren Ji Hospital Affiliated to Shanghai Jiao Tong University
Shanghai
About this study
Official title: Clinical Exploratory Study of YOLT-202 in the Treatment of Alpha-1 Antitrypsin Deficiency (AATD)
This is a single-arm, open-label, single-dose, dose-escalation exploratory study to evaluate the safety and tolerability of a single dose of YOLT-202 in patients with AATD and determine the optimal biologically active dose (OBD) of YOLT-202.
Read the detailed description
This is a single-arm, open-label, single-dose, dose-escalation exploratory study to evaluate the safety and tolerability of a single dose of YOLT-202 in patients with AATD, determine the OBD of YOLT-202, and preliminarily assess the impact of a single dose of YOLT-202 on changes in FEV1 and FEV1/FVC ratio from baseline after bronchodilator use.
Note: The OBD is defined as the dose achieving either a blood functional-AAT/total-AAT protein ratio of 50%-95% at Day 21 post-dose, or a blood total-AAT protein concentration ≥ 11 μM at Day 21 post-dose. OBD ≤ maximum tolerated dose (MTD).
In this study, the maximum screening period of the main study is 60 days, the treatment day is D0, and the safety follow-up period is up to Week 52 after administration. In the main study, when OBD is achieved, additional subjects will be added to the dose group (the sponsor and the investigator will jointly negotiate the specific number of subjects) for further verification. After completing safety follow-up, subjects may voluntarily receive a second dose of the investigational drug at the OBD level based on comprehensive assessments of efficacy, safety, and PK/PD data.
After the end of the main study, the subjects will undergo long-term follow-up.
- Conditions
- Alpha-1 Antitrypsin Deficiency (AATD)
- Being tested
- YOLT-202
- Medical subject headings
- alpha 1-Antitrypsin Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
YOLT-202Drug
Also called AATD-YOLT-202-001
The IP is administered intravenously at the predetermined dose; Administration frequency: Once
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Experimental | Dose groups: 35mg, 45mg, 55mg, TBD (During the dose-escalation process, the investigator and the sponsor may decide, based on actual circumstances, whether to add new dose groups or repeat completed dose groups for the exploratory study). Receives: Drug: YOLT-202 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of YOLT-202 in subjects after administration
Numbers and percentages of patients with adverse events (AE)
Measured: Baseline to 52 weeks post-dose
Secondary outcomes (5)
Pharmacokinetics parameter of YOLT-202
Post-dose plasma concentration (Cmax)
Measured: 30 minutes pre-dose, 2 hours, 6 hours, 24 hours, 48 hours, 72 hours, 168 hours, 336 hours and 504 hours post-dose
Pharmacokinetic (PK) parameter of YOLT-202
Evaluate the time of maximum concentration (tmax)
Measured: 30 minutes pre-dose, 2 hours, 6 hours, 24 hours, 48 hours, 72 hours, 168 hours, 336 hours and 504 hours post-dose
Pharmacokinetic (PK) parameter of YOLT-202
To evaluate the area under curve (AUC)
Measured: 30 minutes pre-dose, 2 hours, 6 hours, 24 hours, 48 hours, 72 hours, 168 hours, 336 hours and 504 hours post-dose
Pharmacokinetic (PK) parameters of YOLT-202
To evaluate elimination half-life (t1/2)
Measured: 30 minutes pre-dose, 2 hours, 6 hours, 24 hours, 48 hours, 72 hours,168 hours,336 hours and 504 hours post-dose
Changes in blood AAT protein level
Total -AAT level over time
Measured: Weeks 1, 2, 3 and 52 post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2025
- Study start18 Jun 2025
- Primary completionJan 2027 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alpha-1 Antitrypsin Deficiency (AATD)Studies of the same condition, open and under way.
- More trials run by RenJi HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RenJi Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07193615
- Sponsor's protocol ID
- AATD-YOLT-202-001
- Acronym
- AATD
- Status last verified
- Sep 2025
- First submitted
- 7 Jul 2025
- Last updated
- 26 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Exploratory Study of YOLT-202 in the Treatment of Alpha-1 Antitrypsin Deficiency (AATD)
- ClinicalTrials.gov ID
- NCT07193615
- Acronym / sponsor ID
- AATD / AATD-YOLT-202-001
- Conditions
- Alpha-1 Antitrypsin Deficiency (AATD)
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- RenJi HospitalUniversity, hospital or other
- Study start
- 18 Jun 2025 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 26 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-arm, open-label, single-dose, dose-escalation exploratory study to evaluate the safety and tolerability of a single dose of YOLT-202 in patients with AATD and determine the optimal biologically active dose (OBD) of YOLT-202.
Detailed description
This is a single-arm, open-label, single-dose, dose-escalation exploratory study to evaluate the safety and tolerability of a single dose of YOLT-202 in patients with AATD, determine the OBD of YOLT-202, and preliminarily assess the impact of a single dose of YOLT-202 on changes in FEV1 and FEV1/FVC ratio from baseline after bronchodilator use.
Note: The OBD is defined as the dose achieving either a blood functional-AAT/total-AAT protein ratio of 50%-95% at Day 21 post-dose, or a blood total-AAT protein concentration ≥ 11 μM at Day 21 post-dose. OBD ≤ maximum tolerated dose (MTD).
In this study, the maximum screening period of the main study is 60 days, the treatment day is D0, and the safety follow-up period is up to Week 52 after administration. In the main study, when OBD is achieved, additional subjects will be added to the dose group (the sponsor and the investigator will jointly negotiate the specific number of subjects) for further verification. After completing safety follow-up, subjects may voluntarily receive a second dose of the investigational drug at the OBD level based on comprehensive assessments of efficacy, safety, and PK/PD data.
After the end of the main study, the subjects will undergo long-term follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Drug: YOLT-202Dose groups: 35mg, 45mg, 55mg, TBD (During the dose-escalation process, the investigator and the sponsor may decide, based on actual circumstances, whether to add new dose groups or repeat completed dose groups for the exploratory study). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male or female (inclusive) aged ≥ 18 and ≤ 70 years old at the time of signing informed consent.
- Diagnosed with AATD and genetically confirmed as homozygous PiZZ mutation.
- Blood total AAT level < 11 μM or equivalent protein in mg/dL.
- Patients receiving augmentation therapy must be willing to discontinue it at least 6 weeks prior to signing the informed consent form (ICF) and throughout the study period, unless clinically indicated.
Key exclusion criteria (32 listed)
- Body mass index (BMI) > 35 kg/m2.
- Patients who have undergone lung or liver transplantation, are on the waiting list for lung or liver transplantation, or have had lung volume reduction surgery (LVRS).
- Clinical evidence of severe bronchiectasis, as judged by the investigator (e.g., excessive sputum production or recurrent infections requiring antibiotics [> 4 times per year]).
- FEV1 ≤ 30% of predicted value after bronchodilator use at screening
- Liver disease with any of the following:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| YOLT-202Also: AATD-YOLT-202-001The IP is administered intravenously at the predetermined dose; Administration frequency: Once | Drug | Single arm |
Primary outcome
Safety of YOLT-202 in subjects after administration
Time frame: Baseline to 52 weeks post-dose
Numbers and percentages of patients with adverse events (AE)
5 secondary outcomes
Pharmacokinetics parameter of YOLT-202
Time frame: 30 minutes pre-dose, 2 hours, 6 hours, 24 hours, 48 hours, 72 hours, 168 hours, 336 hours and 504 hours post-dose
Pharmacokinetic (PK) parameter of YOLT-202
Time frame: 30 minutes pre-dose, 2 hours, 6 hours, 24 hours, 48 hours, 72 hours, 168 hours, 336 hours and 504 hours post-dose
Pharmacokinetic (PK) parameter of YOLT-202
Time frame: 30 minutes pre-dose, 2 hours, 6 hours, 24 hours, 48 hours, 72 hours, 168 hours, 336 hours and 504 hours post-dose
Pharmacokinetic (PK) parameters of YOLT-202
Time frame: 30 minutes pre-dose, 2 hours, 6 hours, 24 hours, 48 hours, 72 hours,168 hours,336 hours and 504 hours post-dose
Changes in blood AAT protein level
Time frame: Weeks 1, 2, 3 and 52 post-dose
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing YOLT-202 in people with Alpha-1 Antitrypsin Deficiency (AATD), run by RenJi Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 26 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of YOLT-202 in subjects after administration (time frame: Baseline to 52 weeks post-dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2025.