Alpha 1-Antitrypsin DeficiencyPhase 1Serpentine-1NCT06049082
A Study of KB408 for the Treatment of Alpha-1 Antitrypsin Deficiency
A Phase 1 study testing KB408 (Nebulization) in people with Alpha 1-Antitrypsin Deficiency, run by Krystal Biotech, Inc. at 3 sites in United States.
Trial summary
The Sponsor is developing KB408, a replication-defective, non-integrating herpes simplex virus type 1 (HSV-1)-derived vector engineered to deliver functional full-length human SERPINA1 to the airways of people with alpha-1 antitrypsin deficiency (AATD) via nebulization. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Alpha 1-Antitrypsin Deficiency
- What is being tested?
- KB408 (Nebulization)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 3 sitesUnited States
- Study dates
- 15 Feb 2024to Dec 2026
- Phase
- 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
- The subject or legally authorized representative must have read, understood, and signed an Institutional Review Board (IRB) approved Informed Consent Form and must be willing and able to comply with study procedures and instructions.
- Subject is aged ≥18 to ≤70 years, at the time of informed consent.
- Subject has a genetically confirmed diagnosis of AATD with a PI*ZZ or PI*ZNull genotype.
- Cohort 2b and Cohort 3: Subjects receiving AAT augmentation therapy must be willing to washout for at least 10 days prior to Screening and be willing to remain off augmentation therapy for the duration of the study.
- Cohort 2b and Cohort 3: Serum AAT level <11 μM at Screening.
- Willing to remain on a stable regimen of treatment during the study.
- Resting oxygen saturation ≥92% on room air at Screening.
- Clinically stable and in good general health, except for AATD, as determined by the Investigator.
Who cannot join
- Pulmonary function test with percent predicted forced expired volume in 1 second (ppFEV1) after inhalation of a bronchodilator is <40% at Screening.
- Diffusing capacity of the lungs for carbon monoxide (DLCO) <30 percent predicted (historical DLCO within 2 years prior to Screening without any intervening change in clinical status since the measurement was taken, or as measured at Screening).
- Known ongoing or history of clinically significant pulmonary impairment other than AATD.
- A pulmonary exacerbation within six weeks (42 days) of first dose.
- Initiation of any new chronic therapy or any change in ongoing therapy routine within 28 days of first dose.
- Participation in another interventional clinical study or treatment with an investigational agent within 30 days or 5 half-lives, whichever is longer, of first dose. Previous treatment with a genetic therapy for AATD, where the investigational product was demonstrated to be non-efficacious, is not exclusionary.
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- History of or listed for solid organ transplantation or has undergone major lung surgery (e.g., lobectomy) within 6 months of first dose.
- Any clinical condition or illness (including a history or current evidence of substance abuse or dependence) that, in the opinion of the Investigator, would impact a subject's ability to complete all study-related procedures and/or poses an additional risk to the assessment of safety of KB408.
- An active oral herpes infection 30 days prior to the first dose.
- Clinically significant hepatic dysfunction defined as any one of the following:
- AST and ALT ≥3× upper limit of normal (ULN) at Screening
- Total bilirubin ≥2× ULN at Screening (unless associated with Gilbert's syndrome)
- Evidence of liver cirrhosis with clinical manifestations of portal hypertension (e.g., ascites, encephalopathy, variceal hemorrhage)
- History of cigarette smoking or any other tobacco use, or use of e-cigarettes or other recreational inhalant, within 6 months of Screening.
- Unwilling to refrain from smoking, e-cigarette use, or vaping throughout the duration of the study.
- A positive urine cotinine result that is consistent with active smoking at Screening. (A positive cotinine test due to nicotine replacement therapy for the purpose of smoking cessation, as attested by the Investigator, is allowed.)
- Abnormal hematology or chemistry testing at Screening as defined below, or any other clinically significant abnormalities that the Investigator believes may interfere with the assessment of safety of the study treatment.
- Platelet count <100×10^9/L
- Hemoglobin <9 g/dL
- White blood cell count <3 or >15×10^9/L
- Sodium <130 or >150 mmol/L
- Potassium <3 or >5.5 mmol/L
- Carbon dioxide <16 mmol/L
- Creatinine >2 mg/dL
- Subject is known to be noncompliant or is unlikely to comply with the requirements of the study protocol, in the opinion of the Investigator.
- Females who are pregnant or nursing.
- Subject who is unwilling to comply with contraception requirements per protocol
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
Medical University of South Carolina
Charleston, South Carolina, 29425
Charlton Strange, MD
Charlton Strange, MD
- Recruiting
University of Florida, Gainesville
Gainesville, Florida, 32610
Allison Faunce, 352-273-8666, Allison.Faunce@medicine.ufl.edu
Jorge Lascano, MD
- Recruiting
Renovatio Clinical
The Woodlands, Texas, 77380
Dustyn Tobin, 713-703-2398, dustyn.tobin@renovatioclinical.com
Ather J Siddiqi, MD
About this study
Official title: A Phase 1 Study of Inhaled KB408 for the Treatment of Alpha-1 Antitrypsin Deficiency
The Sponsor is developing KB408, a replication-defective, non-integrating herpes simplex virus type 1 (HSV-1)-derived vector engineered to deliver functional full-length human SERPINA1 to the airways of people with alpha-1 antitrypsin deficiency (AATD) via nebulization. This study is designed to evaluate safety and pharmacodynamics of KB408 in adults with AATD with a PI*ZZ or PI*ZNull genotype. Three planned dose levels of KB408 will be evaluated in single dose escalation cohorts. Repeat dosing will be evaluated at the mid dose level. Subjects taking intravenous AAT augmentation therapy are not required to wash out from IV AAT in the low and mid dose cohorts. In the repeat dose and the high dose cohorts, subjects must wash out from IV AAT for at least 10 days, as applicable.
- Conditions
- Alpha 1-Antitrypsin Deficiency
- Being tested
- KB408 (Nebulization)
- 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.
KB408 (Nebulization)Drug
Nebulized solution of KB408, a replication-defective HSV-1 vector expressing full length human SERPINA1
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Low dose KB408 | Experimental | Single dose of KB408 (low dose) Receives: Drug: KB408 (Nebulization) |
| Cohort 2: Mid dose KB408 | Experimental | Single dose of KB408 (mid dose) Receives: Drug: KB408 (Nebulization) |
| Cohort 3: High dose KB408 | Experimental | Single dose of KB408 (high dose) Receives: Drug: KB408 (Nebulization) |
| Cohort 2b: Mid dose KB408 | Experimental | Multiple doses of KB408 (mid dose) Receives: Drug: KB408 (Nebulization) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate safety and tolerability of KB408 based upon assessment of adverse events (frequency, severity, relatedness), and changes from baseline in vital signs, ECG, spirometry, and clinical laboratory test results
Number of subjects with treatment related adverse events as assessed by NCI-CTCAE v5
Measured: 2 months (Cohorts 1, 2, 3); 3 months (Cohort 2b)
Secondary outcomes (4)
To assess the effect of KB408 on serum alpha-1 antitrypsin (AAT) concentration
Change from baseline in serum AAT levels
Measured: 2 months (Cohorts 1, 2, 3); 3 months (Cohort 2b)
To assess the effect of KB408 on plasma neutrophil elastase (NE) concentration
Change from baseline in plasma NE levels
Measured: 2 months (Cohorts 1, 2, 3); 3 months (Cohort 2b)
To evaluate the effect of KB408 on AAT concentration in the lung
Change from baseline in AAT levels in bronchoalveolar lavage fluid
Measured: 2 months (Cohorts 1, 2, 3); 3 months (Cohort 2b)
To evaluate the effect of KB408 on NE concentration in the lung
Change from baseline in NE levels in bronchoalveolar lavage fluid
Measured: 2 months (Cohorts 1, 2, 3); 3 months (Cohort 2b)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2023
- Study start15 Feb 2024
- Primary completionDec 2025 (estimated)
- Study completionDec 2026 (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 DeficiencyStudies of the same condition, open and under way.
- More trials run by Krystal Biotech, Inc.The 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Krystal Biotech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Sweet, MD, PhD, Study director, Director of Clinical Development
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06049082
- Sponsor's protocol ID
- KB408-01
- Acronym
- Serpentine-1
- Status last verified
- Jul 2025
- First submitted
- 15 Sep 2023
- Last updated
- 22 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- 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 22 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of Inhaled KB408 for the Treatment of Alpha-1 Antitrypsin Deficiency
- ClinicalTrials.gov ID
- NCT06049082
- Acronym / sponsor ID
- Serpentine-1 / KB408-01
- Conditions
- Alpha 1-Antitrypsin Deficiency
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Krystal Biotech, Inc.Industry (pharma, biotech, devices)
- Study start
- 15 Feb 2024 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 21 Sep 2023 (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.
The Sponsor is developing KB408, a replication-defective, non-integrating herpes simplex virus type 1 (HSV-1)-derived vector engineered to deliver functional full-length human SERPINA1 to the airways of people with alpha-1 antitrypsin deficiency (AATD) via nebulization. This study is designed to evaluate safety and pharmacodynamics of KB408 in adults with AATD with a PI*ZZ or PI*ZNull genotype. Three planned dose levels of KB408 will be evaluated in single dose escalation cohorts. Repeat dosing will be evaluated at the mid dose level. Subjects taking intravenous AAT augmentation therapy are not required to wash out from IV AAT in the low and mid dose cohorts. In the repeat dose and the high dose cohorts, subjects must wash out from IV AAT for at least 10 days, as applicable.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Low dose KB408 | Experimental | Drug: KB408 (Nebulization)Single dose of KB408 (low dose) |
| Cohort 2: Mid dose KB408 | Experimental | Drug: KB408 (Nebulization)Single dose of KB408 (mid dose) |
| Cohort 3: High dose KB408 | Experimental | Drug: KB408 (Nebulization)Single dose of KB408 (high dose) |
| Cohort 2b: Mid dose KB408 | Experimental | Drug: KB408 (Nebulization)Multiple doses of KB408 (mid dose) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- The subject or legally authorized representative must have read, understood, and signed an Institutional Review Board (IRB) approved Informed Consent Form and must be willing and able to comply with study procedures and instructions.
- Subject is aged ≥18 to ≤70 years, at the time of informed consent.
- Subject has a genetically confirmed diagnosis of AATD with a PI*ZZ or PI*ZNull genotype.
- Cohort 2b and Cohort 3: Subjects receiving AAT augmentation therapy must be willing to washout for at least 10 days prior to Screening and be willing to remain off augmentation therapy for the duration of the study.
- Cohort 2b and Cohort 3: Serum AAT level <11 μM at Screening.
Key exclusion criteria (27 listed)
- Pulmonary function test with percent predicted forced expired volume in 1 second (ppFEV1) after inhalation of a bronchodilator is <40% at Screening.
- Diffusing capacity of the lungs for carbon monoxide (DLCO) <30 percent predicted (historical DLCO within 2 years prior to Screening without any intervening change in clinical status since the measurement was taken, or as measured at Screening).
- Known ongoing or history of clinically significant pulmonary impairment other than AATD.
- A pulmonary exacerbation within six weeks (42 days) of first dose.
- Initiation of any new chronic therapy or any change in ongoing therapy routine within 28 days of first dose.
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 |
|---|---|---|
| KB408 (Nebulization)Nebulized solution of KB408, a replication-defective HSV-1 vector expressing full length human SERPINA1 | Drug | Cohort 1: Low dose KB408, Cohort 2: Mid dose KB408, Cohort 2b: Mid dose KB408, Cohort 3: High dose KB408 |
Primary outcome
To evaluate safety and tolerability of KB408 based upon assessment of adverse events (frequency, severity, relatedness), and changes from baseline in vital signs, ECG, spirometry, and clinical laboratory test results
Time frame: 2 months (Cohorts 1, 2, 3); 3 months (Cohort 2b)
Number of subjects with treatment related adverse events as assessed by NCI-CTCAE v5
4 secondary outcomes
To assess the effect of KB408 on serum alpha-1 antitrypsin (AAT) concentration
Time frame: 2 months (Cohorts 1, 2, 3); 3 months (Cohort 2b)
To assess the effect of KB408 on plasma neutrophil elastase (NE) concentration
Time frame: 2 months (Cohorts 1, 2, 3); 3 months (Cohort 2b)
To evaluate the effect of KB408 on AAT concentration in the lung
Time frame: 2 months (Cohorts 1, 2, 3); 3 months (Cohort 2b)
To evaluate the effect of KB408 on NE concentration in the lung
Time frame: 2 months (Cohorts 1, 2, 3); 3 months (Cohort 2b)
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 22 Jul 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.
David Sweet, MD, PhD study director
Director of Clinical Development
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing KB408 (Nebulization) in people with Alpha 1-Antitrypsin Deficiency, run by Krystal Biotech, Inc. at 3 sites in United States.
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 8 inclusion and 27 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: looking for participants now, as of the sponsor's last update on 22 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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?
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.
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 David Sweet, MD, PhD (412-586-5830, dsweet@krystalbio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate safety and tolerability of KB408 based upon assessment of adverse events (frequency, severity, relatedness), and changes from baseline in vital signs, ECG, spirometry, and clinical laboratory test results (time frame: 2 months (Cohorts 1, 2, 3); 3 months (Cohort 2b)). 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 22 Jul 2025.