Clinical trial NCT04596319: Ph 1/2 Study Evaluating Safety and Tolerability of Inhaled AP-PA02 in Subjects With Chronic Pseudomonas Aeruginosa Lung Infections and Cystic Fibrosis
Official title: A Phase 1b/2a, Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety and Tolerability of AP-PA02 Multi-Phage Therapeutic Candidate for Inhalation in Subjects With Cystic Fibrosis and Chronic Pulmonary Pseudomonas Aeruginosa (Pa) Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cystic Fibrosis
Pseudomonas Aeruginosa
Pseudomonas
Lung Infection
Lung Infection Pseudomonal
Keywords: phage
bacteriophage
cystic fibrosis
Pseudomonas
Pseudomonas aeruginosa
Lead sponsor: Armata Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Cystic Fibrosis Foundation
First posted: 2020-10-22
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled
Primary purpose: TREATMENT

Brief summary: Phase 1b/2a, double-blind, randomized, placebo-controlled, single and multiple ascending dose study to evaluate the safety, tolerability and phage recovery profile of AP-PA02 multi-bacteriophage therapeutic candidate administered by inhalation in subjects with cystic fibrosis and chronic pulmonary Pseudomonas aeruginosa (PA) infection.

Detailed description: The study consists of two parts. Subjects with Cystic Fibrosis and chronic pulmonary Pseudomonas aeruginosa (PA) infection will be enrolled in either Part 1 (single-ascending dose cohorts) or Part 2 (multiple-ascending dose cohorts).

Part 1 will evaluate single doses of AP-PA02 at two ascending dose levels, administered by inhalation. Treatment assignment will be randomized, double-blind, placebo-controlled in each of two ascending dose cohorts. Part 2 will also be double-blinded, randomized, placebo controlled, and will evaluate the safety and efficacy of multiple doses of AP-PA02 in each of two ascending dose level cohorts.

Subjects in both Parts 1 and 2 will be followed for approximately 4 weeks and evaluated for safety, tolerability, phage titer profile and immunogenicity.

Eligibility criteria: Key Inclusion Criteria:

* ≥ 18 years old
* Body mass index (BMI) of ≥ 18 kg/m2
* Documented diagnosis of CF
* Evidence of chronic pulmonary Pseudomonas aeruginosa infection
* Willing to undergo sputum induction procedures at designated study visits, and willing to provide expectorated sputum samples at all other timepoints (for subjects who are able to expectorate)
* For SAD: FEV1 ≥ 60% of predicted normal \[per Global Lung Function Initiative (GLI) standards\] at Screening
* For MAD: FEV1 ≥ 40% of predicted normal \[per Global Lung Function Initiative (GLI) standards\] at Screening
* Adequate renal function

Key Exclusion Criteria:

* Recent significant weight loss
* Abnormal vital signs at Screening
* History of prolonged QT syndrome
* Use of supplemental oxygen during the day at rest
* Abnormal liver function tests greater than 3X the upper limit of normal (ULN)
* Recent oral or IV antibiotics received for acute pulmonary exacerbation. Inhaled antibiotic use for chronic suppression of P. aeruginosa is acceptable.
* Recent clinically significant infection requiring systemic antimicrobial therapy
* Currently receiving anti-pseudomonal antibiotic treatment for acute sinusitis.
* Currently receiving systemic corticosteroids
* Currently receiving treatment for active infection with nontuberculous mycobacteria (NTM), Staphylococcus aureus, or Burkholderia cepacia complex lung infection
* Currently receiving treatment for aspergillosis or ABPA (allergic bronchopulmonary aspergillosis)
* Initiation of a CFTR potentiator/corrector therapy, such as Trikafta®, less than 90 days prior to Screening
* Acquired or primary immunodeficiency syndromes
* Active pulmonary malignancy (primary or metastatic)
* History of lung transplantation
* Recent hemoptysis
* Female pregnant or breastfeeding
* Heavy smoker

Primary outcomes:
measure: Incidence and Severity Treatment Emergent Adverse Events (TEAEs)
timeFrame: Day 1 pre-dose through End of Study Visit (28 days post last dose of study drug), up to 4 weeks for single ascending dose and up to 5.5 weeks for multiple ascending dose.
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Boise
country: United States
facility: St. Luke's Cystic Fibrosis Center of Idaho
state: Idaho
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: The University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Harper University Hospital
state: Michigan
city: New Brunswick
country: United States
facility: Rutgers Robert Wood Johnson Medical School
state: New Jersey
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: The Hospital of the University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Armata Pharmaceuticals, Inc.
name: Mina Pastagia, MD, MS
role: STUDY_DIRECTOR
References: