Alpha-1 Antitrypsin Deficiency (AATD)Phase 1/2NCT07850076
A Trial Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of CTX460 in Adults With Emphysema Associated With Severe Alpha-1 Antitrypsin Deficiency (AATD)
A Phase 1/2 study testing CTX460 in people with Alpha-1 Antitrypsin Deficiency (AATD), run by CRISPR Therapeutics.
Trial summary
A Study of CTX460 in Adults with Emphysema Associated with Severe Alpha-1 Antitrypsin Deficiency (AATD). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Alpha-1 Antitrypsin Deficiency (AATD)
- What is being tested?
- CTX460
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- No sites listed yet
- Study dates
- 31 Oct 2026to 30 Jun 2030
- Phase
- Phase 1/2
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age: ≥18 and ≤75 years.
- Able to provide written informed consent.
- Diagnosis of AATD with PiZZ homozygous genotype.
- Serum total AAT level <11µM in the absence of augmentation.
- Emphysema on a CT scan at screening.
- A postbronchodilator forced expiratory volume in 1 second (FEV1) ≥30% of predicted.
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- Body weight ≥50 kg.
- All male participants must agree to the use of a highly effective method of contraception and their female partners who are women of childbearing potential (WoCBP) are recommended to use a highly effective method of contraception from consent through 6 months after CTX460 infusion.
- In Phase 1, female participants must not be WoCBP
- In Phase 2, All female participants are eligible if they:
- Are not pregnant or breastfeeding and
- Agree to the use of a highly effective method of contraception, as defined in the protocol, from consent through 6 months after CTX460 infusion or are postmenopausal, as defined in the protocol.
- Participants agree to abstain from alcohol for 2 weeks before and 2 weeks after CTX460 infusion.
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests, contraceptive guidelines, and other trial procedures.
Who cannot join
- Received augmentation therapy within the 6 weeks prior to CTX460 infusion
- Lung or liver transplant or on waiting list for lung or liver transplant
- Moderate to severe lung disease other than COPD that may confound results as per investigator discretion
- Evidence of significant liver fibrosis/cirrhosis
- Participants with cardiovascular disease
- Participation in another clinical trial with an investigational drug/product within 30 days of screening or <5 half-lives of the investigational agent
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- Exclude participants with an active infection of HBV and HCV
- Exclude participants with uncontrolled HIV
- Systemic steroid use within 30 days prior to CTX460 administration; inhaled steroids are permitted
- Prior treatment with therapy using viral vectors or intended to permanently change a participant's DNA (except for CTX460).
- Receipt of LNP vaccines ≤4 weeks prior to screening.
- Participants with a history of medically significant or severe reactions to any LNP-based product, including severe hypersensitivity reactions or anaphylaxis.
- History of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the trial or pose an additional risk in administering trial drug to the participant.
- Active malignancy within past 3 years with the exception of recent basal cell or squamous cell of the skin.
- Smokers/vapers (nonsmoking/nonvaping for at least 12 months prior to screening are eligible).
- Participants with specified laboratory abnormalities at screening, confirmed by repeat testing when clinically appropriate.
- Participants with alcohol use disorder or alcoholic hepatitis within one year prior to screening.
- In Phase 1 only, females of childbearing potential or breastfeeding females.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Official Title: A Phase 1/2 Multicenter, Open-label, First-in-Human Trial Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of CTX460, a Lipid Nanoparticle Formulation of SyNTase Editing Components for In Vivo Editing of the Serine Protease Inhibitor A1 (SERPINA1) Gene in Adults With Emphysema Associated With Severe Alpha-1 Antitrypsin Deficiency (AATD)
A Study of CTX460 in Adults with Emphysema Associated with Severe Alpha-1 Antitrypsin Deficiency (AATD).
Read the detailed description
This is a dose finding and expansion study of CTX460 in Adults with Emphysema Associated with Severe Alpha-1 Antitrypsin Deficiency (AATD). Participants will receive CTX460 via intravenous (IV) infusion.
- Conditions
- Alpha-1 Antitrypsin Deficiency (AATD)
- Being tested
- CTX460
- 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.
CTX460Drug
CTX460 is a lipid nanoparticle (LNP) formulation of synthetic nucleotide template polymerase (SyNTase) editor for in vivo gene editing of the serine protease inhibitor A1 (SERPINA1) gene in adults with emphysema associated with severe alpha-1 antitrypsin deficiency (AATD).
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 | Experimental | Phase 1 begins with dose escalation based on a single infusion of CTX460. Receives: Drug: CTX460 |
| Phase 2 | Experimental | Recommended Phase 2 dose of CTX460. Receives: Drug: CTX460 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: To evaluate the safety and tolerability of CTX460 in adults with emphysema associated with severe AATD and to determine the recommended Phase 2 dose(s)
Incidence of DLTs and frequency of AEs
Measured: From CTX460 infusion up to 36 months
Phase 2: To assess the efficacy of CTX460 in adults with severe AATD and emphysema
Absolute blood levels of total AAT at Month 6
Measured: 6 months from CTX460 infusion
Secondary outcomes (9)
Phase 1: To assess the preliminary efficacy of CTX460
Absolute blood levels of total AAT at Month 6
Measured: 6 months from CTX460 infusion
Phase 2: To further characterize the safety of CTX460
Frequency and severity of clinically significant laboratory abnormalities, and clinically significant abnormal vital signs
Measured: From CTX460 infusion up to 36 months
Phase 1/2: To assess the efficacy of CTX460
Rate of change in lung density (g/L per year) as measured by centralized, standardized CT lung densitometry
Measured: From CTX460 infusion up to 36 months
Phase 1/2: To assess the efficacy of CTX460
Time to first moderate or severe COPD exacerbation
Measured: From CTX460 infusion up to 36 months
Phase 1/2: To assess the efficacy of CTX460
Annual rate of moderate or severe COPD exacerbations
Measured: From CTX460 infusion up to 36 months
Phase 1/2: To assess the efficacy of CTX460
Change from baseline in St. George's Respiratory Questionnaire score over time
Measured: From CTX460 infusion up to 36 months
Phase 1/2: To assess the efficacy of CTX460
Change from baseline in FEV1 over time
Measured: From CTX460 infusion up to 36 months
Phase 1/2: To assess the effect of CTX460 on blood PD markers
Blood levels of Z-AAT, M-AAT, and fAAT over time
Measured: From CTX460 infusion up to 36 months
Phase 1/2: To characterize the PK of CTX460
Plasma levels of LNPs over time (ionizable lipid and PEG-lipid)
Measured: From CTX460 infusion up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2026
- Study start31 Oct 2026 (estimated)
- Primary completion30 Jun 2030 (estimated)
- Study completion30 Jun 2030 (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.
- 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
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- CRISPR Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07850076
- Sponsor's protocol ID
- CRSP-460-101
- Status last verified
- Sep 2026
- First submitted
- 21 Sep 2026
- Last updated
- 30 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Official Title: A Phase 1/2 Multicenter, Open-label, First-in-Human Trial Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of CTX460, a Lipid Nanoparticle Formulation of SyNTase Editing Components for In Vivo Editing of the Serine Protease Inhibitor A1 (SERPINA1) Gene in Adults With Emphysema Associated With Severe Alpha-1 Antitrypsin Deficiency (AATD)
- ClinicalTrials.gov ID
- NCT07850076
- Acronym / sponsor ID
- CRSP-460-101
- Conditions
- Alpha-1 Antitrypsin Deficiency (AATD)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- CRISPR TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 31 Oct 2026 (estimated)
- Primary completion
- 30 Jun 2030 (estimated)
- Study completion
- 30 Jun 2030 (estimated)
- First posted
- 30 Sep 2026 (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.
A Study of CTX460 in Adults with Emphysema Associated with Severe Alpha-1 Antitrypsin Deficiency (AATD).
Detailed description
This is a dose finding and expansion study of CTX460 in Adults with Emphysema Associated with Severe Alpha-1 Antitrypsin Deficiency (AATD). Participants will receive CTX460 via intravenous (IV) infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1 | Experimental | Drug: CTX460Phase 1 begins with dose escalation based on a single infusion of CTX460. |
| Phase 2 | Experimental | Drug: CTX460Recommended Phase 2 dose of CTX460. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Age: ≥18 and ≤75 years.
- Able to provide written informed consent.
- Diagnosis of AATD with PiZZ homozygous genotype.
- Serum total AAT level <11µM in the absence of augmentation.
- Emphysema on a CT scan at screening.
Key exclusion criteria (18 listed)
- Received augmentation therapy within the 6 weeks prior to CTX460 infusion
- Lung or liver transplant or on waiting list for lung or liver transplant
- Moderate to severe lung disease other than COPD that may confound results as per investigator discretion
- Evidence of significant liver fibrosis/cirrhosis
- Participants with cardiovascular disease
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 |
|---|---|---|
| CTX460CTX460 is a lipid nanoparticle (LNP) formulation of synthetic nucleotide template polymerase (SyNTase) editor for in vivo gene editing of the serine protease inhibitor A1 (SERPINA1) gene in adults with emphysema associated with severe alpha-1 antitrypsin deficiency (AATD). | Drug | Phase 1, Phase 2 |
Primary outcome
Phase 1: To evaluate the safety and tolerability of CTX460 in adults with emphysema associated with severe AATD and to determine the recommended Phase 2 dose(s)
Time frame: From CTX460 infusion up to 36 months
Incidence of DLTs and frequency of AEs
Phase 2: To assess the efficacy of CTX460 in adults with severe AATD and emphysema
Time frame: 6 months from CTX460 infusion
Absolute blood levels of total AAT at Month 6
9 secondary outcomes
Phase 1: To assess the preliminary efficacy of CTX460
Time frame: 6 months from CTX460 infusion
Phase 2: To further characterize the safety of CTX460
Time frame: From CTX460 infusion up to 36 months
Phase 1/2: To assess the efficacy of CTX460
Time frame: From CTX460 infusion up to 36 months
Phase 1/2: To assess the efficacy of CTX460
Time frame: From CTX460 infusion up to 36 months
Phase 1/2: To assess the efficacy of CTX460
Time frame: From CTX460 infusion up to 36 months
Phase 1/2: To assess the efficacy of CTX460
Time frame: From CTX460 infusion up to 36 months
Phase 1/2: To assess the efficacy of CTX460
Time frame: From CTX460 infusion up to 36 months
Phase 1/2: To assess the effect of CTX460 on blood PD markers
Time frame: From CTX460 infusion up to 36 months
Phase 1/2: To characterize the PK of CTX460
Time frame: From CTX460 infusion up to 36 months
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 30 Sep 2026.
- 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.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CTX460 in people with Alpha-1 Antitrypsin Deficiency (AATD), run by CRISPR Therapeutics.
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 14 inclusion and 18 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: opening soon, as of the sponsor's last update on 30 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Clinical Trials (877-214-4634, medicalaffairs@crisprtx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: To evaluate the safety and tolerability of CTX460 in adults with emphysema associated with severe AATD and to determine the recommended Phase 2 dose(s) (time frame: From CTX460 infusion up to 36 months). The study lists 2 primary outcomes in all. 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 30 Sep 2026.