A Study Assessing KB407 for the Treatment of Cystic Fibrosis

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

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

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Biological: KB407 (Nebulization)

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Brittani Agostini, RN, CCRC; Phone Number: 412-586-5830; Email: bagostini@krystalbio.com
• Study Contact Backup: Name: David Sweet, MD, PhD; Phone Number: 412-586-5830; Email: dsweet@krystalbio.com

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • University of Florida, Gainesville
      • Principal Investigator: Jorge Lascano, MD
      • Contact: Alexa Smith; Phone Number: 352-273-5085; Email: alexa.howell@ufl.edu
  • Idaho
    • Boise, Idaho, United States, 83712
      • Recruiting
      • St. Lukes CF Center of Idaho
      • Principal Investigator: Karen Miller, MD
      • Contact: Dixie Durham; Phone Number: 208-381-7092; Email: durhamd@slhs.org
  • Illinois
    • Northfield, Illinois, United States, 60093
      • Recruiting
      • The Cystic Fibrosis Institute
      • Contact: Karolina Roszko; Email: research@wecare4lungs.com
      • Principal Investigator: Steven Boas, MD
  • New York
    • Hawthorne, New York, United States, 10532
      • Recruiting
      • New York Medical College/ Boston Children's Health Physicians
      • Principal Investigator: John Welter, MD
      • Contact: Armando Ramirez, CRC; Phone Number: 914-504-0152; Email: armando.ramirez@bchphysicians.org
    • New York, New York, United States, 10028
      • Recruiting
      • Northwell Health Physicians
      • Contact: Teresa Demarco; Phone Number: 212-434-4790; Email: tdemarco3@northwell.edu
      • Principal Investigator: Maria Berdella, MD
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Atrium Health Wake Forest Baptist Medical Center
      • Contact: Christian Smith; Phone Number: 336-173-8550; Email: chnsmith@wakehealth.edu
      • Principal Investigator: Chad R Marion, DO, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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
2. Subjects aged 18 years or older at the time of Informed Consent

3. 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
4. Clinically stable in the opinion of the Investigator
5. Percent predicted FEV1 ≥40% and ≤90% of the predicted normal for age, gender, and height at Screening
6. Resting oxygen saturation ≥92% on room air at Screening

Exclusion Criteria:

1. 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
2. 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
3. Treatment for Mycobacterium abscessus within 3 months prior to the first dose or more than two pulmonary exacerbations with a history of Burkholderia cenocepacia infection within 6 months prior to the first dose
4. 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
5. History of or listed for solid organ transplantation
6. 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
7. An active oral herpes infection 30 days prior to the first dose
8. Women who are pregnant or nursing
9. Subject who is unwilling to comply with contraception requirements per protocol
10. 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
11. Subject has a known hypersensitivity to inhaled glycerol
12. Subject is known to be noncompliant or is unlikely to comply with the requirements of the study protocol in the opinion of the Investigator
13. Bronchoscopy participants only: Unable to tolerate bronchoscopy procedure and airway sampling, in the opinion of the Investigator
14. Cohort 4 participants only: Subjects who are ineligible for, do not tolerate, or do not benefit from modulator therapy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (open label); A single administration of KB407	Biological: KB407 (Nebulization); Nebulized solution of KB407, a replication-defective HSV-1 expressing full length human CFTR
Experimental: Cohort 2 (open label); Two administrations of KB407	Biological: KB407 (Nebulization); Nebulized solution of KB407, a replication-defective HSV-1 expressing full length human CFTR
Experimental: Cohort 3 (open label); Four administrations of KB407	Biological: KB407 (Nebulization); Nebulized solution of KB407, a replication-defective HSV-1 expressing full length human CFTR
Experimental: Cohort 4 (open label); Four consecutive administrations of KB407 followed by weekly administration for up to 6 months	Biological: KB407 (Nebulization); Nebulized solution of KB407, a replication-defective HSV-1 expressing full length human CFTR

What is the study measuring?

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	6 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	6 months

Collaborators and Investigators

• Sponsor: Krystal Biotech, Inc.
• Investigators: Study Director: David Chien, MD, Senior Vice President of Clinical Development

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: August 15, 2022
• First Submitted That Met QC Criteria: August 15, 2022
• First Posted (Actual): August 17, 2022

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cystic Fibrosis
• Other Study ID Numbers: KB407-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No