A Phase 2, Randomized, Double-blind, Placebo-controlled, Repeat-dose Study of KB001-A in Subjects with Cystic Fibrosis Infected with Pseudomonas aeruginosa

Study ID
STU 092012-060

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • Clements University Hospital
  • UT Southwestern-Clinical Translational Research Center (CTRC)
  • UT Southwestern Ambulatory Services
  • Children's Medical Center-Dallas

Contact
Ashley Keller
214-648-2817
ashley.keller@utsouthwestern.edu

Principal Investigator
Raksha Jain

Summary

This is a Phase 2, randomized, double-blind, placebo-controlled, repeat-dose study in
approximately 180 subjects with CF infected with Pa, to be conducted in approximately
90 centers globally. The study will consist of a 2-week Screening Period, a 16-week
Treatment Period, and a 4-week Follow-up Period. eligible subjects will be randomized
1:1 to receive up to 5 iV infusions of 10 mg/kg KB001-a (up to a maximum of 800 mg
per dose) or placebo during the 16-week Treatment Period. all subjects will continue
treatment with their regularly scheduled inhaled antibiotic (concurrent with study drug
treatment) during the first 4 weeks of the Treatment Period, after which they will
discontinue their scheduled inhaled antibiotic treatment. Treatment Period visits will
include assessments of respiratory tract signs and symptoms, antibiotic use, spirometry,
KB001-a immunogenicity, hospitalizations ([Greater Than]6 hours in a hospital or medical center),
and aes, and other safety evaluations. in a substudy, additional evaluations will be
performed in approximately 60 of the subjects (approximately 30 subjects per cohort)
including eCGs for safety; induced sputum tests for cytology, inflammatory markers, PK
(KB001-a concentration), and microbiology blood tests for PK (KB001-a
concentration) and inflammatory markers. Following the Treatment Period, all subjects
will undergo a 4-week Follow-up Period, with visit assessments similar to those
conducted during the Treatment Period.

induced sputum will be collected in accordance with Cystic Fibrosis Foundation
Therapeutic Development network (CFF TDn) standard operating procedures (SoPs),
and sent to designated laboratories for analyses. a study flow diagram is presented in
Figure 6.

our site is not participating in the sub-study procedures of this study.

Primary endpoint
The primary endpoint is time-to-need for antibiotic treatment (iV, inhaled, or oral) for worsening of respiratory tract signs and symptoms over 16 weeks.

Secondary endpoints of this study are:
* Rate of aes/serious adverse events (Saes) and shifts in laboratory values (including eCGs for substudy subjects)
* Change from baseline in respiratory symptoms (CFRSD)
* Rate of respiratory events requiring antibiotics
* Proportion of subjects requiring antibiotics for worsening of respiratory tract signs and symptoms
* immunogenicity of KB001-a
* Substudy subjects only:
x Change in blood and sputum inflammatory markers (hsCPR for all subjects)
x Change in blood and sputum KB001-a concentrations
* Change from baseline in FeV1 % predicted
* Change from baseline in other spirometry values (e.g., FVC)
* Rate of hospitalization ([Greater Than]6 hours in a hospital or medical center) for respiratory events,
* Time-to-need for antibiotics (iV, inhaled, or oral) for worsening of respiratory tract signs and symptoms, through the Follow-up Period
* Change in body weight from baseline
* Respiratory exacerbations (RSSQ, using Fuchs and Rosenfeld criteria)
* Substudy subjects only:
x Quantitative changes in Pa cfu in sputum
x Changes in airway microbiome

Participant Eligibility

Subjects must meet all of the following criteria to be eligible for this study.
1. Willingness to sign written informed consent, or ability to provide assent when
applicable.
2. Age >=12 years and <=50 years. Individuals with CF who are older than 50 years may
participate if they have been treated with 2 or more courses of antibiotics (IV and/or
oral) for respiratory signs and symptoms (CF exacerbation) in the 12 months before
the Screening Visit.
3. Confirmed diagnosis of CF based on the following criteria:
x Positive sweat chloride >60 mEq/L (by pilocarpine iontophoresis), and/or
x A genotype with 2 identifiable mutations consistent with CF, and
x One or more clinical features consistent with the CF phenotype
4. At least 2 respiratory tract cultures in the previous 12 months, with Pa present in
>50% of cultures. The most recent positive Pa culture must be within 12 weeks
before the Screening Visit (or obtain a positive culture at screening).
5. FEV1 % predicted >=40% and <=80%, based on Wang[Single Quote]s equations for males 12 to
17 years and females 12 to 15 years, and on Hankinson[Single Quote]s equations for older
participants (Hankinson 1999, Wang 1993). For subjects <18 years of age who
require daily inhaled antibiotics, the range of FEV1 % predicted must be >=60% and
<=80%. In addition, subjects with FEV1% predicted that is >80% and <=100% may
participate if they have been treated with 2 or more courses of antibiotics (IV and/or
oral) for respiratory signs and symptoms (CF exacerbation) in the 12 months before
the Screening Visit.
6. Received antipseudomonal inhaled antibiotics for the equivalent of 8 weeks or
greater in the 26 weeks before the Day 0 Visit. Note: Chronic daily antipseudomonal
inhaled antibiotic regimens are allowed.
7. Ability to understand and comply with study requirements, including completion of
visits and questionnaires.