bacteriophage therapy / Walter Reed Army Institute of Research, BiomX - LARVOL DELTA

APT.DFO.001: Bacteriophage Therapy in Patients With Diabetic Foot Osteomyelitis (clinicaltrials.gov) - P2 | N=41 | Terminated | Sponsor: Adaptive Phage Therapeutics, Inc. | Recruiting ➔ Terminated | Trial primary completion date: Apr 2024 ➔ Jan 2025 | Phase classification: P2b ➔ P2 | N=126 ➔ 41 | Trial completion date: Dec 2024 ➔ May 2025; Study reached minimum enrollment threshold

Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Trial termination • Inflammation

Antibiotics and non-traditional antimicrobial agents for pseudomonas aeruginosa in clinical phases 1, 2, and 3 trials. (PubMed, Expert Opin Investig Drugs) - "Traditional agents in clinical development include β-lactam/β-lactamase inhibitors (funobactam, taniborbactam, QPX2014-xeruborbactam), aminoglycosides (apramycin), polymyxin derivatives (upleganan, MRX-8, and SPR741), fluoroquinolones (MP-376), and lipopolysaccharide transport inhibitors (murepavadin). Non-traditional antibiotics in clinical development include anti-virulence agents (fluorothiazinone), monoclonal antibodies (INFEX-702, TRL-1068, and CMTX-101), bacteriophages (AP-PA02, YPT-01, BX004-A, and WRAIR-PAM-CF1), and miscellaneous agents (AR-501, PLG-0206, SNSP-113, OligoG CF-5/20, and ALX-009). A considerable number of antimicrobial agents, some with novel mechanisms of action, are in clinical phases of development for treating Pseudomonas aeruginosa infections. The urgent need for more therapeutic options necessitates the rapid optimization of progress to introduce new agents into clinical practice."

Journal • Review • Infectious Disease

A Phase 1b/2 Trial of the Safety and Microbiological Activity of Bacteriophage Therapy in Cystic Fibrosis Subjects Colonized With Pseudomonas Aeruginosa (clinicaltrials.gov) - P1/2 | N=73 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Completed

Trial completion • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

A Phase 1b/2 Trial of the Safety and Microbiological Activity of Bacteriophage Therapy in Cystic Fibrosis Subjects Colonized With Pseudomonas Aeruginosa (clinicaltrials.gov) - P1/2 | N=73 | Active, not recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Active, not recruiting

Enrollment closed • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

A Phase 1b/2 Trial of the Safety and Microbiological Activity of Bacteriophage Therapy in Cystic Fibrosis Subjects Colonized With Pseudomonas Aeruginosa (clinicaltrials.gov) - P1/2 | N=72 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Dec 2024 ➔ Apr 2025 | Trial primary completion date: Dec 2024 ➔ Apr 2025

Trial completion date • Trial primary completion date • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

A Phase 1b/2 Trial of the Safety and Microbiological Activity of Bacteriophage Therapy in Cystic Fibrosis Subjects Colonized With Pseudomonas Aeruginosa (clinicaltrials.gov) - P1/2 | N=72 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Jun 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Feasibility of using bacteriophage therapy to treat Staphylococcal aureus fracture-related infections. (PubMed, Injury) - "Our findings show that Staphylococcal bacteriophage therapeutics are readily available for S. aureus FRI clinical isolates. However, when correlated with the current barriers to using bacteriophages to treat FRI, designated Staphylococcal bacteriophage cocktails with broad spectrum activity should be created."

Journal • Infectious Disease • Musculoskeletal Diseases • Orthopedics

ACTIVE1: Bacteriophage Therapy in First Time Chronic Prosthetic Joint Infections (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: Adaptive Phage Therapeutics, Inc. | N=20 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Infectious Disease

ACTIVE2: Bacteriophage Therapy in Patients With Prosthetic Joint Infections (PJI) (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Adaptive Phage Therapeutics, Inc. | N=90 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Infectious Disease

A Phase 1b/2 Trial of the Safety and Microbiological Activity of Bacteriophage Therapy in Cystic Fibrosis Subjects Colonized With Pseudomonas Aeruginosa (clinicaltrials.gov) - P1/2 | N=72 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Phase classification: P1b/2 ➔ P1/2

Phase classification • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

APT.DFO.001: Bacteriophage Therapy in Patients With Diabetic Foot Osteomyelitis (clinicaltrials.gov) - P2b | N=126 | Recruiting | Sponsor: Adaptive Phage Therapeutics, Inc. | Phase classification: P2a ➔ P2b | Trial primary completion date: Oct 2023 ➔ Apr 2024

Phase classification • Trial primary completion date • Inflammation • CRP

A Phase 1b/2 Trial of the Safety and Microbiological Activity of Bacteriophage Therapy in Cystic Fibrosis Subjects Colonized With Pseudomonas Aeruginosa (clinicaltrials.gov) - P1b/2 | N=72 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Feb 2024 ➔ Jun 2024 | Trial primary completion date: Feb 2024 ➔ Jun 2024

Trial completion date • Trial primary completion date • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Refractory Pseudomonas aeruginosa infections treated with phage PASA16: A compassionate use case series. (PubMed, Med) - "PASA16 with antibiotics was found to be relatively successful in patients for whom traditional treatment approaches have failed previously. Such pre-phase-1 cohorts can outline potential clinical protocols and facilitate the design of future trials."

Journal • Infectious Disease

ACTIVE2: Bacteriophage Therapy in Patients With Prosthetic Joint Infections (PJI) (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Adaptive Phage Therapeutics, Inc. | Not yet recruiting ➔ Recruiting | Phase classification: P2/3 ➔ P2 | N=280 ➔ 90 | Trial completion date: Oct 2025 ➔ Jul 2027 | Trial primary completion date: Oct 2024 ➔ Jul 2025

Enrollment change • Enrollment open • Phase classification • Trial completion date • Trial primary completion date • Infectious Disease

Bacteriophage Therapy in Patients With Urinary Tract Infections (clinicaltrials.gov) - P1/2 | N=1 | Terminated | Sponsor: Adaptive Phage Therapeutics, Inc. | N=156 ➔ 1 | Active, not recruiting ➔ Terminated; Study terminated due to a change in development strategy.

Enrollment change • Trial termination • Infectious Disease • Nephrology

Bacteriophage Therapy in Patients With Urinary Tract Infections (clinicaltrials.gov) - P1/2 | N=156 | Active, not recruiting | Sponsor: Adaptive Phage Therapeutics, Inc. | Trial primary completion date: Nov 2022 ➔ Feb 2023

Trial primary completion date • Infectious Disease • Nephrology

Adaptive Phage Therapeutics Announces First Patient Dosed in the PHAGE Clinical Trial Evaluating Phage Therapy in Cystic Fibrosis-related Respiratory Infection (Businesswire) - "Adaptive Phage Therapeutics...today announced the first patient has been dosed in the PHAGE clinical trial, evaluating bacteriophage therapy in adults with cystic fibrosis (CF) who carry Pseudomonas aeruginosa (P. aeruginosa) in their lungs. The trial is evaluating whether the bacteriophage, or 'phage,' therapy is safe and able to reduce the amount of bacteria in the lungs of volunteers. The PHAGE trial is enrolling CF patients who chronically harbor P. aeruginosa in their respiratory tracts. Participants receive WRAIR-PAM-CF1 as a single IV infusion at one of three dosage levels. Researchers will gather data on safety and microbiological activity; how the phages function in the body; how the investigational therapy affects the participants’ lung function; whether the therapy works differently on P. aeruginosa from different geographical regions; and whether the therapy changes participants’ overall quality of life."

Trial status • Cystic Fibrosis

Bacteriophage Therapy in Patients With Urinary Tract Infections (clinicaltrials.gov) - P1/2 | N=156 | Active, not recruiting | Sponsor: Adaptive Phage Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2023 ➔ Feb 2023

Enrollment closed • Trial completion date • Infectious Disease • Nephrology

Recurrent ESBL Escherichia coli Urosepsis in a Pediatric Renal Transplant Patient Treated With Antibiotics and Bacteriophage Therapy. (PubMed, Pediatr Infect Dis J) - "This case highlights the challenges of treating recurrent ESBL E. coli infections in a pediatric renal transplant patient and provides evidence that phage therapy may prove useful in such cases."

Journal • Gastrointestinal Disorder • Infectious Disease • Pediatrics • Transplantation

NIH-supported clinical trial of phage therapy for cystic fibrosis begins (National Institute of Health) - "Enrollment has begun in an early-stage clinical trial evaluating bacteriophage therapy in adults with cystic fibrosis (CF) who carry Pseudomonas aeruginosa (P. aeruginosa) in their lungs. The trial is evaluating whether the bacteriophage, or 'phage,' therapy is safe and able to reduce the amount of bacteria in the lungs of volunteers. The trial is being conducted by the Antibacterial Resistance Leadership Group (ARLG)(link is external), funded by the National Institute of Allergy and Infectious Diseases. Investigators aim to enroll up to 72 adults at 16 CF centers across the United States....The trial will begin as a Phase 1b trial and will expand to a Phase 2 trial. First, two participants per dosage level will receive an unblinded infusion of the therapeutic and will be closely monitored for four days thereafter. If no serious safety issues are identified, researchers will begin enrolling additional participants..."

Enrollment open • Cystic Fibrosis • Infectious Disease

A Phase 1b/2 Trial of the Safety and Microbiological Activity of Bacteriophage Therapy in Cystic Fibrosis Subjects Colonized With Pseudomonas Aeruginosa (clinicaltrials.gov) - P1b/2 | N=72 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Jan 2025 ➔ Feb 2024

Trial completion date • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

A Phase 1b/2 Trial of the Safety and Microbiological Activity of Bacteriophage Therapy in Cystic Fibrosis Subjects Colonized With Pseudomonas Aeruginosa (clinicaltrials.gov) - P1b/2 | N=72 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Not yet recruiting ➔ Recruiting

Enrollment open • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

APT.DFO.001: Bacteriophage Therapy in Patients With Diabetic Foot Osteomyelitis (clinicaltrials.gov) - P2a | N=126 | Recruiting | Sponsor: Adaptive Phage Therapeutics, Inc. | N=75 ➔ 126

Enrollment change • Inflammation • CRP

Bacteriophage Therapy in Patients With Prosthetic Joint Infections (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: Adaptive Phage Therapeutics, Inc. | N=78 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Infectious Disease • Orthopedics

Impact of Bacterial Phenotypic Variation with Bacteriophage therapy: A Pilot Study with Prosthetic Joint Infection Isolates. (PubMed, Int J Infect Dis) - "Variations of bacteriophage activity can occur between the different in vivo clinical environments which is likely secondary to different glycosylation patterns of teichoic acid. Consequently, if discordant activity is present then retreating with bacteriophages that have activity is likely needed for effective, reproducible outcomes."

Journal • Infectious Disease