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

Sponsor

Armata Pharmaceuticals, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04596319

Collaborator

Cystic Fibrosis Foundation (Other)

Enrollment

Locations

Arms

14.3

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis Pseudomonas Aeruginosa Pseudomonas Lung Infection Lung Infection Pseudomonal	Biological: AP-PA02 Other: Placebo	Phase 1/Phase 2

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 three ascending dose levels, administered by inhalation. Treatment assignment will be randomized, double-blind, placebo-controlled in each of three 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 three 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 Design

Study Type:

Interventional

Anticipated Enrollment :

48 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, double-blind, placebo-controlledRandomized, double-blind, placebo-controlled

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 22, 2020

Anticipated Primary Completion Date :

Mar 1, 2022

Anticipated Study Completion Date :

Mar 1, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Incidence of Treatment Emergent Adverse Events (Safety and Tolerability) of single and multiple doses of AP-PA02 administered by inhalation [Day 1 pre-dose through End of Study Visit (Day 29 for SAD, Day 31 for MAD)]
Incidence and severity of treatment-emergent adverse events

Secondary Outcome Measures

Part 2 (MAD) Only: Explore P. aeruginosa recovery in sputum following multiple doses of AP-PA02 administered by inhalation [Baseline (Day -1) through Visit 7 (Day 17)]
Change in P. aeruginosa colony-forming units (CFU) per gram of sputum

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)
FEV1 ≥ 60% 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
2	University of South Florida	Tampa	Florida	United States	33606
3	St. Luke's Cystic Fibrosis Center of Idaho	Boise	Idaho	United States	83712
4	Northwestern University	Chicago	Illinois	United States	60208
5	University of Iowa	Iowa City	Iowa	United States	52242
6	Johns Hopkins University	Baltimore	Maryland	United States	21205
7	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
8	Boston Children's Hospital	Boston	Massachusetts	United States	02115
9	Rutgers Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08901
10	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
11	The Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
12	Medical University of South Carolina	Charleston	South Carolina	United States	29425
13	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
14	University of Texas Southwestern	Dallas	Texas	United States	75390
15	University of Washington	Seattle	Washington	United States	98195
16	University of Wisconsin	Madison	Wisconsin	United States	53792-9988