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

Phase 1

Completed

• Conditions: Pseudomonas; Cystic Fibrosis; Pseudomonas Aeruginosa; Lung Infection; Lung Infection Pseudomonal
• Interventions: Biological: AP-PA02; Other: Placebo

• Registration Number: NCT04596319
• Lead Sponsor: Armata Pharmaceuticals, Inc.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-10-15
• Study First Submitted QC: 2020-10-20
• Study First Posted: 2020-10-22
• Study Start: 2020-12-22
• Primary Completion: 2022-12-14
• Study Completion: 2022-12-14
• Results First Submitted: 2023-12-04
• Status Verified: 2024-01
• Results First Submitted QC: 2024-01-04
• Last Update Submitted: 2024-01-04
• Results First Posted: 2024-01-31
• Last Update Posted: 2024-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AP-PA02	AP-PA02	Anti-pseudomonal bacteriophage
Placebo	Placebo	Inactive isotonic solution

Primary Outcome Measures

Name	Time	Method
Incidence and Severity Treatment Emergent Adverse Events (TEAEs)	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.	Incidence and severity of treatment emergent adverse events of single and multiple doses of AP-PA02 administered by inhalation

Trial Locations

Locations (20)

Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States

University of Washington; 🇺🇸 Seattle, Washington, United States

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

St. Luke's Cystic Fibrosis Center of Idaho; 🇺🇸 Boise, Idaho, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

Rutgers Robert Wood Johnson Medical School; 🇺🇸 New Brunswick, New Jersey, United States

University Hospitals Cleveland Medical Center; 🇺🇸 Cleveland, Ohio, United States

The Hospital of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Texas Southwestern; 🇺🇸 Dallas, Texas, United States

The University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States

New York Medical College; 🇺🇸 Valhalla, New York, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Wisconsin; 🇺🇸 Madison, Wisconsin, United States

University of South Florida; 🇺🇸 Tampa, Florida, United States

Harper University Hospital; 🇺🇸 Detroit, Michigan, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States