Trial design of bacteriophage therapy for nontuberculous mycobacteria pulmonary disease in cystic fibrosis: The POSTSTAMP study

Jerry A Nick; Stacey L Martiniano; Valerie K Lovell; Brian Vestal; Katie Poch; Silvia M Caceres; Noel M Rysavy; Vinicius Calado de Moura; Jennifer J Gilick; Kenneth C Malcolm; Jessica Pacheco; Anita G Amin; Delphi Chatterjee; Charles L Daley; Shannon Kasperbauer; Jane E Gross; Emily Armantrout; Keira A Cohen; Allison Keck; Jill M Vandalfsen; Amalia S Magaret; Nikita Midamba; Claire Chapdu; Antao Gao; Jane E Hill; Krista G Freeman; Madison Cristinziano; Carlos Guerrero; Deborah Jacobs-Sera; Michael J Lauer; Maggie Viland; Graham F Hatfull; Investigators of the Cystic Fibrosis NTM Consortium

doi:10.1016/j.jcf.2025.03.669

Trial design of bacteriophage therapy for nontuberculous mycobacteria pulmonary disease in cystic fibrosis: The POSTSTAMP study

J Cyst Fibros. 2025 Apr 12:S1569-1993(25)00765-9. doi: 10.1016/j.jcf.2025.03.669. Online ahead of print.

Authors

Jerry A Nick¹, Stacey L Martiniano², Valerie K Lovell³, Brian Vestal⁴, Katie Poch⁵, Silvia M Caceres⁵, Noel M Rysavy⁵, Vinicius Calado de Moura⁵, Jennifer J Gilick⁵, Kenneth C Malcolm⁶, Jessica Pacheco⁷, Anita G Amin⁸, Delphi Chatterjee⁸, Charles L Daley⁶, Shannon Kasperbauer⁶, Jane E Gross⁹, Emily Armantrout⁵, Keira A Cohen¹⁰, Allison Keck², Jill M Vandalfsen¹¹, Amalia S Magaret¹¹, Nikita Midamba¹¹, Claire Chapdu¹¹, Antao Gao¹², Jane E Hill¹², Krista G Freeman¹³, Madison Cristinziano¹³, Carlos Guerrero¹³, Deborah Jacobs-Sera¹³, Michael J Lauer¹³, Maggie Viland¹³, Graham F Hatfull¹³; Investigators of the Cystic Fibrosis NTM Consortium

Collaborators

Investigators of the Cystic Fibrosis NTM Consortium:
G Marty Solomon¹⁴, Carmen Reyes¹⁵, Douglas J Conrad¹⁶, Silvia Delgado Villalta¹⁷, Manu Jain¹⁸, Noah Lechtzin¹⁹, Rebecca E Cagnina²⁰, Lindsay J Caverly²¹, Brian P O'Sullivan²², Emily A DiMango²³, Jennifer L Goralski²⁴, Charles R Esther²⁴, Karen S McCoy²⁵, Joseph M Pilewski²⁶, Raksha Jain²⁷, Zachary L Weintraub²⁸, Ronald L Gibson²⁹, Kathleen J Ramos³⁰

Affiliations

¹ Department of Medicine, National Jewish Health, Denver, CO 80206, USA; Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address: nickj@njhealth.org.
² Department of Pediatrics, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO 80045, USA.
³ Department of Medicine, National Jewish Health, Denver, CO 80206, USA. Electronic address: lovellv@njhealth.org.
⁴ Center for Genes, Environment, and Health, National Jewish Health, Denver, CO 80206, USA.
⁵ Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
⁶ Department of Medicine, National Jewish Health, Denver, CO 80206, USA; Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
⁷ Investigational Drug Services Pharmacy, National Jewish Health, Denver, CO 80206, USA.
⁸ Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO 80523, USA.
⁹ Department of Medicine, National Jewish Health, Denver, CO 80206, USA; Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA.
¹⁰ Department of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
¹¹ Cystic Fibrosis Foundation Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle, WA, USA.
¹² Department of Chemical and Biological Engineering, University of British Columbia, Vancouver BC V6T 1Z4, CA, USA.
¹³ Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
¹⁴ University of Alabama Birmingham, Birmingham, AL, USA.
¹⁵ Children's Hospital of Los Angeles, Los Angeles, CA, USA.
¹⁶ University of California San Diego, San Diego, CA, USA.
¹⁷ University of Florida, Gainesville, FL, USA.
¹⁸ Northwestern University, Chicago, IL, USA.
¹⁹ Johns Hopkins University, Baltimore, MD, USA.
²⁰ Boston Children's Hospital, Brigham & Women's Hospital, Boston, MA, USA.
²¹ University of Michigan, Ann Arbor, MI, USA.
²² Dartmouth Hitchcock Medical Center, Lebanon, NH, USA.
²³ Columbia University, NY, NY, USA.
²⁴ University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
²⁵ Nationwide Children's Hospital, Columbus, OH, USA.
²⁶ University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
²⁷ University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
²⁸ University of Vermont Medical Center, Burlington, VT, USA.
²⁹ Children's Hospital, Seattle, WA, USA.
³⁰ University of Washington, Seattle, WA, USA.

PMID: 40222858
DOI: 10.1016/j.jcf.2025.03.669

Abstract

Bacteriophages (phages) are viruses that selectively infect bacteria and have been utilized to treat Mycobacterium abscessus (Mab) with varying success. The POSTSTAMP study is an ongoing, multi-site phage therapy protocol for treatment-refractory pulmonary Mab disease in people with cystic fibrosis (pwCF). Participants (n = 10) are prospectively assessed while utilizing FDA investigational new drug (IND) approval for compassionate use. Participants are >6 years old, able to produce sputum, have been treated with guideline-based antibiotic therapy (GBT) for >12 months without culture conversion, and are currently receiving GBT with at least 3 and ≥ 80 % positive Mab cultures in the prior year. At enrollment, an isolate is assessed for the availability of lytic phage(s). Open-label phage therapy consists of 1 or 2 phages administered intravenously twice daily for 52 weeks. Participants without a phage match will be followed on GBT as a comparison group. Follow-up visits will occur monthly, with one follow-up visit at completion and intermittent visits for a year after phage therapy. Efficacy will be assessed by culture, standard clinical measures and a patient-reported quality-of-life instrument. Frequency of Mab detection 12 months prior to treatment will be compared with the 12-month period beginning 6 months after treatment initiation. Individual-level tests of difference in percent positive cultures within subjects will be used to identify "responders". Collectively and including all persons, a mixed-effect model will be used to test for a difference in frequency of Mab detection following treatment or without treatment. The trial will also test for markers of treatment failure and pathogen adaptation in participants who did not achieve microbiological response, and will monitor for safety and tolerance.

Keywords: Biomarkers; Cystic fibrosis; M. abscessus; Nontuberculous mycobacterial (NTM); Phage therapy.