Mycobacteriophage Treatment of Non-tuberculosis Mycobacteria (POSTSTAMP)

A Prospective Standardized Assessment of People With Cystic Fibrosis and Non-tuberculosis Mycobacteria Pulmonary Disease Undergoing Treatment With Mycobacteriophage (POSTSTAMP)

About 10 people with cystic fibrosis (CF) and persistent Nontuberculosis mycobacteria (NTM) infection despite treatment will be screened to find out if their NTM infection has at least one mycobacteriophage that is effective in killing the mycobacteria. Individuals who are found to have at least one phage will be offered assistance in pursuing FDA approval for treatment via expanded-access Individual New Drug (IND) for compassionate-use. They will receive phage treatment for 1 year along with their guideline-based antibiotics for NTM. Individuals who are not identified as having a phage match will be followed as they continue to receive guideline based antibiotic therapy for 1 year. All subjects, including those who do not have a phage match will continue to be observed for the duration of the study, or about 1 year.

Study Overview

• Status: Enrolling by invitation
• Conditions: Mycobacterium Infections; Cystic Fibrosis; Nontuberculous Mycobacterial Lung Disease; Nontuberculous Mycobacterium Infection; Mycobacterium; Pulmonary
• Intervention / Treatment: Biological: mycobacteriophage

Detailed Description

About 10 people with cystic fibrosis and NTM infection with positive sputum cultures after a minimum of 12 months of guideline-based therapy will be screened to find out if their NTM infection has at least one mycobacteriophage that is known to be effective against the NTM. Individuals who have been found to have at least one effective phage will be offered assistance in pursuing FDA approval for phage treatment through a compassionate-use Individual New Drug (IND). These subjects will receive phage treatment for 1 year along with their guideline-based antibiotics for NTM. Individuals who are not identified as having a phage match will continue to receive guideline based antibiotic therapy. All subjects, receiving phage or not, will be observed and assessed, including collection of specimens, to evaluate response to treatment.

• Study Type: Observational
• Enrollment (Estimated): 10

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles
    • San Diego, California, United States, 92103
      • University of California
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
    • Denver, Colorado, United States, 80045
      • Childrens Hospital Colorado
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • John Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Childrens Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Nationwide Children's Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • Southwestern Medical Center at Dallas
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants with a diagnosis of CF who meet all of the inclusion and none of the exclusion criteria will be eligible for participation in this study.

Description

Inclusion Criteria:

1. Written informed consent (and assent when applicable) obtained from participant or participant's legal representative
2. Enrolled in the CFF Patient Registry (CFF PR)
3. Be willing to adhere to study procedures in the context of clinical care, and other protocol requirements
4. Male or female participant ≥ 6 years of age at enrollment who are able to reliably expectorate sputum and/or willing to undergo sputum induction (if necessary)
5. Diagnosis of CF consistent with the 2017 CFF Guidelines
6. NTM pulmonary disease on treatment with guideline-based antibiotics for >12 months without consistent conversion of airway cultures to negative.
7. Physician intention to treat NTM with phage therapy (if susceptible)
8. Be willing and able to continue guideline-based antibiotics for NTM concurrent with phage.
9. Documentation of a sufficient number of NTM cultures with a sufficient proportion of positive cultures in the interval 12 months prior to initiation of phage to allow for a within-subject power ≥0.80 to detect a difference in the percent positive NTM cultures in the interval 6-18 months following initiation of phage.

Exclusion Criteria:

1. Pregnant or breastfeeding
2. Prior or ongoing phage therapy for the species of NTM under consideration.
3. History of solid organ or hematological transplantation
4. Has any other condition that, in the opinion of the Site Investigator/designee, would preclude informed consent or assent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
People with cystic fibrosis who are receiving phage treatment for NTM.; People with cystic fibrosis who have identified at least one phage effective against their NTM infection and are receiving treatment with the phage. These subjects will remain on guideline based NTM antibiotic treatment and their standard CF care. They will receive therapeutic phage twice daily for 1 year.	Biological: mycobacteriophage; mycobacteriophage phage that has been found effective in killing participants NTM infection
People with cystic fibrosis who are not receiving phage treatment for NTM.; People with cystic fibrosis who have not identified any phage effective against their NTM infection and are not receiving phage treatment. These subjects will continue with guideline based NTM antibiotic treatment for their NTM disease and standard CF care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence to therapy	Proportion who adhere to the POSTSTAMP protocol based on number of respiratory cultures obtained per year, withdrawals or major deviations from protocol.	Comparing the year of phage therapy to the year prior to start of phage therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phage susceptibility	Proportion of participants with NTM infection susceptible to phage	At the time of enrollment
Culture conversion	Proportion of participants with >12 months of consecutive negative cultures with no subsequent positive cultures.	Any 12 month interval from the start of phage therapy to end of follow-up, an average of about 2 years.
Tolerance of treatment	Proportion requiring antibiotic course change due to intolerance or lack of microbiological conversion (i.e. eradication from sputum)	From enrollment through study completion, an average of about 24-30 months.
Clinical Response (pulmonary function testing)	Within subject change in forced expiratory volume at one second (FEV1) with increase indicating improvement in lung function or FEV1 decrease indicating decline in lung function.	From enrollment through study completion, an average of about 24-30 months.
Microbiologic response to phage	Within-subject change in percent positive (%pos) cultures following phage initiation (or identification that no phage is available), compared to the interval prior to phage initiation (or identification that no phage is available): the period of antibiotic treatment without phage.	A year interval from month 6 of treatment to month 18 following start of phage will be compared to the year prior to start of phage.
Clinical response (BMI)	Within subject change in BMI with decline in BMI as sign of decline or worse outcome.	From enrollment through study completion, an average of about 24-30 months.
Clinical response (CFQR)	Within subject change in Cystic Fibrosis Questionnaire -Research (CFQR) score, with higher score indicating worse symptoms.	From enrollment through study completion, an average of about 24-30 months.
Clinical Response (antibiotic courses for non- NTM exacerbations)	Proportion of non-NTM exacerbations compared to NTM exacerbations.	From enrollment through study completion, an average of about 24-30 months.

Collaborators and Investigators

• Sponsor: National Jewish Health
• Collaborators: Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Jerry Nick, MD, National Jewish Health

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: February 4, 2024
• First Submitted That Met QC Criteria: February 14, 2024
• First Posted (Actual): February 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 21, 2025
• Last Update Submitted That Met QC Criteria: May 20, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: cystic fibrosis; phage; mycobacteriophage
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Lung Diseases; Fibrosis; Infections; Communicable Diseases; Cystic Fibrosis; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous
• Other Study ID Numbers: NTM-OB-17 (PART C)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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