Mycobacteriophage Treatment of Non-tuberculosis Mycobacteria

N/AEnrolling By InvitationNCT06262282

National Jewish Health10 enrolled

Overview

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.

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

Conditions

Cystic Fibrosis Nontuberculous Mycobacterial Lung Disease

Eligibility

Sex: ALLMin age: 6 Years

Medical Language ↔ Plain English

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

Locations (18)

University of Alabama

Birmingham, Alabama, United States

Children's Hospital of Los Angeles

Los Angeles, California, United States

University of California

San Diego, California, United States

Childrens Hospital Colorado

Denver, Colorado, United States

National Jewish Health

Denver, Colorado, United States

University of Florida

Gainesville, Florida, United States

Northwestern University

Chicago, Illinois, United States

John Hopkins University

Baltimore, Maryland, United States

Boston Childrens Hospital

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

...and 8 more locations

Outcomes

Primary Outcomes

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.

Time frame: Comparing the year of phage therapy to the year prior to start of phage therapy

Secondary Outcomes

Phage susceptibility

Proportion of participants with NTM infection susceptible to phage

Time frame: At the time of enrollment

Culture conversion

Proportion of participants with \>12 months of consecutive negative cultures with no subsequent positive cultures.

Time frame: 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)