Ph 1/2 Study Evaluating Safety and Tolerability of Inhaled AP-PA02 in Subjects With Chronic Pseudomonas Aeruginosa Lung Infections and Cystic Fibrosis (SWARM-Pa)

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis; Pseudomonas Aeruginosa; Lung Infection; Pseudomonas; Lung Infection Pseudomonal
• Intervention / Treatment: Biological: AP-PA02; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
  • Florida
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • Idaho
    • Boise, Idaho, United States, 83712
      • St. Luke's Cystic Fibrosis Center of Idaho
  • Illinois
    • Chicago, Illinois, United States, 60208
      • Northwestern University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Harper University Hospital
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Robert Wood Johnson Medical School
  • New York
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Hospital of the University of Pennsylvania
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-9988
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AP-PA02; Anti-pseudomonal bacteriophage	Biological: AP-PA02; Bacteriophage administered via inhalation
Placebo Comparator: Placebo; Inactive isotonic solution	Other: Placebo; Inactive Placebo administered via inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity Treatment Emergent Adverse Events (TEAEs)	Incidence and severity of treatment emergent adverse events of single and multiple doses of AP-PA02 administered by inhalation	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2 (MAD) Only: Explore P. aeruginosa recovery in sputum following multiple doses of AP-PA02 administered by inhalation	Change in P. aeruginosa colony-forming units (CFU) per gram of sputum	Baseline (Day -1) through 14 days post last dose of study drug

Collaborators and Investigators

• Sponsor: Armata Pharmaceuticals, Inc.
• Collaborators: Cystic Fibrosis Foundation
• Investigators: Study Director: Mina Pastagia, MD, MS, Armata Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• Armata Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2020
• Primary Completion (Actual): December 14, 2022
• Study Completion (Actual): December 14, 2022

Study Registration Dates

• First Submitted: October 15, 2020
• First Submitted That Met QC Criteria: October 20, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Estimated): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: cystic fibrosis; Pseudomonas aeruginosa; bacteriophage; phage; Pseudomonas
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Pancreatic Diseases; Fibrosis; Infections; Communicable Diseases; Cystic Fibrosis; Pseudomonas Infections
• Other Study ID Numbers: AP-PA02-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No