Mycobacteriophage Treatment of Non-tuberculosis Mycobacteria
- Conditions
- Cystic FibrosisNontuberculous Mycobacterium InfectionMycobacterium InfectionsMycobacterium; PulmonaryNontuberculous Mycobacterial Lung Disease
- Interventions
- Biological: mycobacteriophage
- Registration Number
- NCT06262282
- Lead Sponsor
- National Jewish Health
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 10
- Written informed consent (and assent when applicable) obtained from participant or participant's legal representative
- Enrolled in the CFF Patient Registry (CFF PR)
- Be willing to adhere to study procedures in the context of clinical care, and other protocol requirements
- 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)
- Diagnosis of CF consistent with the 2017 CFF Guidelines
- NTM pulmonary disease on treatment with guideline-based antibiotics for >12 months without consistent conversion of airway cultures to negative.
- Physician intention to treat NTM with phage therapy (if susceptible)
- Be willing and able to continue guideline-based antibiotics for NTM concurrent with phage.
- 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.
- Pregnant or breastfeeding
- Prior or ongoing phage therapy for the species of NTM under consideration.
- History of solid organ or hematological transplantation
- 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 & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description People with cystic fibrosis who are receiving phage treatment for NTM. mycobacteriophage 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.
- Primary Outcome Measures
Name Time Method Adherence to therapy Comparing the year of phage therapy to the year prior to start of phage therapy Proportion who adhere to the POSTSTAMP protocol based on number of respiratory cultures obtained per year, withdrawals or major deviations from protocol.
- Secondary Outcome Measures
Name Time Method Tolerance of treatment From enrollment through study completion, an average of about 24-30 months. Proportion requiring antibiotic course change due to intolerance or lack of microbiological conversion (i.e. eradication from sputum)
Clinical response (BMI) From enrollment through study completion, an average of about 24-30 months. Within subject change in BMI with decline in BMI as sign of decline or worse outcome.
Culture conversion Any 12 month interval from the start of phage therapy to end of follow-up, an average of about 2 years. Proportion of participants with \>12 months of consecutive negative cultures with no subsequent positive cultures.
Phage susceptibility At the time of enrollment Proportion of participants with NTM infection susceptible to phage
Clinical Response (pulmonary function testing) From enrollment through study completion, an average of about 24-30 months. 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.
Clinical response (CFQR) From enrollment through study completion, an average of about 24-30 months. Within subject change in Cystic Fibrosis Questionnaire -Research (CFQR) score, with higher score indicating worse symptoms.
Clinical Response (antibiotic courses for non- NTM exacerbations) From enrollment through study completion, an average of about 24-30 months. Proportion of non-NTM exacerbations compared to NTM exacerbations.
Microbiologic response to 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. 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.
Trial Locations
- Locations (18)
John Hopkins University
🇺🇸Baltimore, Maryland, United States
Children's Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
University of Vermont
🇺🇸Burlington, Vermont, United States
University of Washington
🇺🇸Seattle, Washington, United States
University of California
🇺🇸San Diego, California, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
University of Alabama
🇺🇸Birmingham, Alabama, United States
Boston Childrens Hospital
🇺🇸Boston, Massachusetts, United States
Childrens Hospital Colorado
🇺🇸Denver, Colorado, United States
Columbia University
🇺🇸New York, New York, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Southwestern Medical Center at Dallas
🇺🇸Dallas, Texas, United States