Bacteriophage Therapy in Patients With Prosthetic Joint Infections (PJI) (ACTIVE2)

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of APT Phage Bank Phage Therapy Versus Placebo in Conjunction With Debridement, Antibiotics, and Implant Retention (DAIR) in Subjects With Chronic Prosthetic Joint Infection (PJI)

This is a study designed to evaluate bacteriophage therapy in patients with chronic prosthetic joint infections.

Study Overview

• Status: Withdrawn
• Conditions: Prosthetic Joint Infection
• Intervention / Treatment: Drug: Placebo; Drug: Bacteriophage

Detailed Description

This is a study designed to evaluate bacteriophage therapy in patients with chronic prosthetic joint infections of the hip or knee caused by at least 1 of the following organisms: Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Streptococcus spp., Enterococcus faecium, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, or Klebsiella pneumoniae.

This study will compare the safety and efficacy of DAIR procedure + Phage Therapy + Antibiotics versus DAIR procedure + Placebo + Antibiotics.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Staci Steele; Phone Number: (606) 992-0589; Email: SSteele@aphage.com

Study Locations

• United States
  • California
    • San Diego, California, United States, 92037
      • University of California San Diego Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Hartford Health Care Bone & Joint Insitute
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Snake River Research
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital of Baltimore
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
    • Boston, Massachusetts, United States, 02120
      • New England Baptist Hospital
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • WVU Medicine JW Ruby Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males or females ≥18 years of age
• Recurrent PJI of the knee or hip
• Female patients of childbearing potential who agree to use contraception.
• Confirmed phage match
• No anticipated need for long-term antibiotics

Exclusion Criteria:

• Soft tissue defect requiring reconstruction
• Hardware misalignment
• Additional orthopedic hardware in connection with the infected prosthesis
• Active infection (other than PJI) requiring long term IV antibiotics
• Unable to tolerate SAT
• Septic shock or hemodynamic instability
• Stage 4 or greater chronic kidney disease
• Liver disease
• Decompensated heart failure
• Positive drug screen
• Receiving chemotherapy
• Immunocompromised
• Treatment with antiviral medication within 2 weeks prior to randomization
• Currently participating in another clinical trial
• Known phage allergy
• Pregnant/ breast feeding
• Lack of capacity to consent

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: DAIR + Phage Treatment + Antibiotics; Phage therapy will be administered in conjunction with antibiotic treatment.	Drug: Bacteriophage; Phage Therapy
Placebo Comparator: DAIR + Placebo + Antibiotics; Placebo will be administered in conjunction with antibiotic treatment.	Drug: Placebo; Placebo; Other Names: Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety and tolerability of phage + DAIR compared with placebo + DAIR in adult subjects with chronic or recalcitrant PJI	Incidence of reactions to study treatment and discontinuation due to adverse events	Day 1 through Week 24
To evaluate the efficacy of phage + DAIR compared with placebo + DAIR in adult subjects with chronic or recalcitrant PJI	Time to recurrence or evidence of infection with the original pathogen at the same joint	Day 1 through 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment success	No recurrence or evidence of infection with the original pathogen at the same joint	Day 1 through 12 months
No recurrence or evidence of infection for any reason	Infection due to the original pathogen or a different pathogen	12 months after DAIR

Collaborators and Investigators

• Sponsor: Adaptive Phage Therapeutics, Inc.
• Investigators: Study Chair: Edward Fang, MD, Adaptive Phage Therapeutics, Chief Medical Officer

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: February 25, 2022
• First Submitted That Met QC Criteria: February 25, 2022
• First Posted (Actual): March 7, 2022

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Knee; Hip; Bacteriophage; Phage; Joint; DAIR; Prosthetic; Prosthetic Joint
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Joint Diseases; Musculoskeletal Diseases; Arthritis; Infections; Communicable Diseases; Arthritis, Infectious
• Other Study ID Numbers: APT.PJI.006

Drug and device information, study documents

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