A Study Assessing KB407 for the Treatment of Cystic Fibrosis

Study Overview
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Brief Summary
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This study will evaluate safety and tolerability of ascending doses of nebulized KB407 in adults with cystic fibrosis.

Official Title
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KB407-02 A Phase 1 Study of Inhaled KB407, a Replication-Defective, Non-Integrating Vector Expressing Human Cystic Fibrosis Transmembrane Conductance Regulator, for the Treatment of Cystic Fibrosis

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Biological: KB407 (Nebulization)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject must have read, understood, and signed an Institutional Review Board/Ethics Committee (IRB/IEC) approved Informed Consent Form and must be able to and willing to follow study procedures and instructions Subjects aged 18 years or older at the time of Informed Consent A confirmed diagnosis of CF as defined by clinical signs and symptoms of CF and at least one of the following: A historical sweat chloride value >60 mmol/L Two copies of a disease causing mutation in the CFTR gene Clinically stable in the opinion of the Investigator Percent predicted FEV1 ≥50% and ≤100% of the predicted normal for age, gender, and height at Screening Resting oxygen saturation ≥92% on room air at Screening Exclusion Criteria: Initiation of any new chronic therapy (eg, CFTR modulator, hypertonic saline, inhaled antibiotic) or any change in chronic therapy (excluding pancreatic enzyme replacement therapy) within 28 days prior to the first dose Hospitalization, sinopulmonary infection, CF exacerbation, or other clinically significant infection or illness 14 days prior to the first dose that, in the opinion of the Investigator, may confound study results Treatment for Burkholderia cenocepacia, Burkholderia dolosa, or Nontuberculosis Mycobacteria infection within 3 months prior to the first dose Participation in another clinical study or treatment with an investigational agent 30 days or 5 half-lives, whichever is longer, prior to the first dose History of or listed for solid organ transplantation Any condition (including a history or current evidence of substance abuse or dependence, uncontrolled asthma, or is considered to be immunocompromised) 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 KB407 An active oral herpes infection 30 days prior to the first dose Has received a vaccine within 72 hours prior to the first dose or has a planned vaccination during the treatment period Women who are pregnant or nursing Subject who is unwilling to comply with contraception requirements per protocol Clinically significant abnormalities of hematology or chemistry testing at Screening that the Investigator believes may interfere with the assessment of safety and/or efficacy of the study treatment Subject has a known hypersensitivity to inhaled glycerol Subject is known to be noncompliant or is unlikely to comply with the requirements of the study protocol in the opinion of the Investigator Bronchoscopy participants only: Unable to tolerate bronchoscopy procedure and airway sampling, in the opinion of the Investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (open label)<br>A single administration of KB407 | Biological: KB407 (Nebulization)<br>* Nebulized solution of KB407, a replication-defective HSV-1 expressing full length human CFTR<br>|
| Experimental: Cohort 2 (open label)<br>Two administrations of KB407 | Biological: KB407 (Nebulization)<br>* Nebulized solution of KB407, a replication-defective HSV-1 expressing full length human CFTR<br>|
| Experimental: Cohort 3 (open label)<br>Four administrations of KB407 | Biological: KB407 (Nebulization)<br>* Nebulized solution of KB407, a replication-defective HSV-1 expressing full length human CFTR<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate safety and tolerability of KB407 based upon assessment of adverse events (frequency, severity, relatedness), and changes from baseline in physical examinations, vital signs, ECG, and clinical laboratory test results | Number of adult subjects with treatment related adverse events as assessed by NCI-CTCAE v5 | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effects of KB407 on pulmonary function, as measured by change from baseline in absolute and percent predicted FEV1 | Assessment of forced expiratory volume, in one second (FEV1,) will be assessed by spirometry as compared to baseline | 2 months |