Mycobacteriophage Treatment of Non-tuberculosis Mycobacteria

Cystic Fibrosis Clinical Trial

— POSTSTAMP  

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06262282
• Other study ID #: NTM-OB-17 (PART C)
• Status: Enrolling by invitation
• Start date: February 5, 2024
• Est. completion date: December 2028

Study information

• Verified date: February 2024
• Source: National Jewish Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Enrolling by invitation
• Enrollment: 10
• Est. completion date: December 2028
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Cystic Fibrosis
• Fibrosis
• Infections
• Lung Diseases
• Mycobacterium Infections
• Mycobacterium Infections, Nontuberculous
• Nontuberculous Mycobacterial Lung Disease
• Nontuberculous Mycobacterium Infection

Intervention

Biological:
• mycobacteriophage
mycobacteriophage phage that has been found effective in killing participants NTM infection

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	John Hopkins University	Baltimore	Maryland
United States	University of Alabama	Birmingham	Alabama
United States	Boston Childrens Hospital	Boston	Massachusetts
United States	University of Vermont	Burlington	Vermont
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Southwestern Medical Center at Dallas	Dallas	Texas
United States	Childrens Hospital Colorado	Denver	Colorado
United States	National Jewish Health	Denver	Colorado
United States	University of Florida	Gainesville	Florida
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Columbia University	New York	New York
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	University of California	San Diego	California
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
National Jewish Health	Cystic Fibrosis Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Phage susceptibility	Proportion of participants with NTM infection susceptible to phage	At the time of enrollment
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.