IV Bacteriophage Therapy for Cystic Fibrosis

No longer recruiting at 45 trial locations

Overseen By Pranita Tamma

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Antibiotics, Antifungals

Disqualifiers: Low weight, Liver issues, Pregnancy, others

Compensation: Varies

Number of Visits: 6

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new therapy called WRAIR-PAM-CF1 for people with Cystic Fibrosis (CF) who have persistent lung infections caused by the bacteria Pseudomonas aeruginosa. The treatment uses bacteriophages, viruses that specifically target and destroy this harmful bacteria, and is administered through an IV. The trial will explore different doses to determine the safest and most effective one. People with CF who regularly face this bacterial infection might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications. However, you must keep your chronic antibiotic regimens constant during the study, meaning you should not change them unless necessary. If you are on chronic suppressive therapy, you must continue it throughout the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that WRAIR-PAM-CF1, a treatment using viruses to target specific bacteria in cystic fibrosis patients, appears safe. In earlier studies, patients tolerated the treatment well, with no serious side effects reported in the first 96 hours after administration. This suggests that the treatment is well-tolerated in the short term.

However, as this is an early-stage trial, more research is needed to fully understand its long-term safety. The current study aims to gather more information, and by participating, individuals will help researchers learn more about the treatment's safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for Cystic Fibrosis?

Researchers are excited about WRAIR-PAM-CF1 because it introduces a novel approach to treating cystic fibrosis by using bacteriophage therapy. Unlike standard antibiotics, which can struggle against antibiotic-resistant bacteria, bacteriophages are viruses that specifically target and destroy bacteria, potentially reducing bacterial infections more effectively. This new mechanism of action could offer a more targeted and efficient way to manage chronic lung infections in cystic fibrosis patients, offering hope for those who may not respond well to conventional treatments. Additionally, bacteriophage therapy might reduce the risk of antibiotic resistance, a significant concern with current treatments.

What evidence suggests that this trial's treatments could be effective for Cystic Fibrosis?

Research has shown that bacteriophage therapy could help treat infections in people with cystic fibrosis (CF). In earlier studies, patients who received this therapy experienced improved lung function, with an average increase of 6% in a key lung function measure called FEV1. This trial will evaluate the effectiveness of WRAIR-PAM-CF1, which targets the bacteria Pseudomonas aeruginosa, in reducing these difficult infections. Participants in this trial will receive either WRAIR-PAM-CF1 or a placebo. Overall, early evidence from other studies suggests that using bacteriophages could be beneficial in managing bacterial infections in CF. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Adults over 18 with Cystic Fibrosis who have had a Pseudomonas aeruginosa infection in the last year, can produce sputum for testing, and are clinically stable. They must not be on new antibiotics or enrolled in other trials within the past month, weigh at least 30 kg, and have reasonable lung function. Pregnant or breastfeeding women and those with severe liver issues or allergies to trial components cannot participate.

Inclusion Criteria

I have been diagnosed with cystic fibrosis based on symptoms and either a sweat test or genetic test.

I am willing and able to follow all study requirements.

I can likely produce enough sputum for a test after a special treatment.

Exclusion Criteria

I am not pregnant, planning to become pregnant, or breastfeeding, and agree to use birth control during the trial.

I haven't taken new antibiotics in the last 30 days, except for ongoing treatments.

I have not been treated for fungal or mycobacterial infections in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of intravenous bacteriophage therapy or placebo

1 day

1 visit (in-person)

Observation

Participants are observed for 30 plus or minus 7 days for safety and microbiological activity

4-5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

5 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• WRAIR-PAM-CF1

Trial Overview The study is examining WRAIR-PAM-CF1 bacteriophage therapy's safety and effectiveness against Pseudomonas aeruginosa in CF patients. Participants will receive one of three doses of this IV treatment or a placebo during different stages to determine the best dose based on safety and microbiological activity.

How Is the Trial Designed?

Group I: Stage 2b Arm 2 Active Control 1 Intervention

WRAIR-PAM-CF1 concentration determined after post stage 2a analysis, administered intravenously with 25 mL of 0.9 percent Sodium Chloride saline solution for 30 mins as a single dosage. N=17

Group II: Stage 1/2a Arm 3 Active Control 1 Intervention

4x10\^8 plaque forming units (PFU) of WRAIR-PAM-CF1 administered intravenously with approximately 25 mL of 0.9 percent Sodium Chloride saline solution for 30 mins as a single dosage. Stage 1: N=2 (sentinel subjects); Stage 2a: N=8

Group III: Stage 1/2a Arm 2 Active Control 1 Intervention

4x10\^7 plaque forming units (PFU) of WRAIR-PAM-CF1 administered intravenously with approximately 25 mL of 0.9 percent Sodium Chloride saline solution for 30 mins as a single dosage. Stage 1: N=2 (sentinel subjects); Stage 2a: N=8

Group IV: Stage 1/2a Arm 4 Active Control 1 Intervention

4x10\^9 plaque forming units (PFU) of WRAIR-PAM-CF1 administered intravenously with approximately 25 mL of 0.9 percent Sodium Chloride saline solution for 30 mins as a single dosage. Stage 1: N=2 (sentinel subjects); Stage 2a: N=8

Group V: Stage 2a Arm 1 Placebo Group 1 Intervention

25 mL of 0.9 percent Sodium Chloride saline solution administered intravenously for 30 mins as a single dosage. N=8

Group VI: Stage 2b Arm 1 Placebo Group 1 Intervention

25 mL of 0.9 percent Sodium Chloride saline solution administered intravenously for 30 mins as a single dosage. N=17

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

Phage therapy significantly reduced lethality, bacterial burden, and inflammation in a cystic fibrosis zebrafish model infected with Pseudomonas aeruginosa, marking the first successful use of this treatment in a CF animal model.

Combining phage therapy with antibiotics enhanced the treatment's effectiveness, suggesting a promising strategy to lower antibiotic doses and treatment duration for P. aeruginosa infections in cystic fibrosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model. Cafora, M., Deflorian, G., Forti, F., et al.[2023]

Bacteriophage therapy has shown promise in reducing bacterial load in cystic fibrosis patients infected with Pseudomonas aeruginosa, with some cases reporting improvements in biofilm reduction and resistance profiles.

While complete eradication of Pseudomonas aeruginosa was rare, the treatment demonstrated potential benefits, indicating that further large-scale trials are necessary to confirm its safety and efficacy for broader use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review on the use of bacteriophage in treating Staphylococcus aureus and Pseudomonas aeruginosa infections in cystic fibrosis. Singh, J., Yeoh, E., Fitzgerald, DA., et al.[2023]

A 26-year-old cystic fibrosis patient with multidrug resistant Pseudomonas aeruginosa pneumonia was successfully treated with intravenous bacteriophage therapy alongside antibiotics, leading to clinical resolution of her infection without adverse events.

Following the bacteriophage therapy, the patient did not experience a recurrence of pneumonia or cystic fibrosis exacerbation for 100 days and later underwent a successful lung transplantation, suggesting that bacteriophage therapy could be a promising option for treating resistant infections in cystic fibrosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful adjunctive use of bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa infection in a cystic fibrosis patient. Law, N., Logan, C., Yung, G., et al.[2020]

Phage therapy shows promise for treating antibiotic-resistant Pseudomonas aeruginosa infections in children with cystic fibrosis, emphasizing the need for continuous treatment due to the emergence of resistant bacteria.

A modular approach using both single and mixed phage preparations can enhance the effectiveness of treatment by rapidly adapting to the lytic activity of phages, potentially overcoming challenges posed by phage-resistant bacterial strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modular Approach to Select Bacteriophages Targeting Pseudomonas aeruginosa for Their Application to Children Suffering With Cystic Fibrosis. Krylov, V., Shaburova, O., Pleteneva, E., et al.[2020]

Bacteriophage therapy shows promise as a potential treatment for multidrug-resistant Pseudomonas aeruginosa in cystic fibrosis patients, as lytic phages can degrade biofilm matrices, but their effectiveness and safety in vivo remain uncertain.

Future clinical research should focus on well-characterized phage cocktails, potentially combined with antibiotics, and tested in both laboratory and animal models to establish reliable treatment protocols for cystic fibrosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges and Promises for Planning Future Clinical Research Into Bacteriophage Therapy Against Pseudomonas aeruginosa in Cystic Fibrosis. An Argumentative Review. Rossitto, M., Fiscarelli, EV., Rosati, P.[2023]

In a review of adverse events (AEs) among 433 children with cystic fibrosis participating in clinical trials, a total of 8,266 AEs were reported, averaging 18.1 AEs per person per year, with respiratory AEs being the most common.

Cough was the most frequently reported respiratory AE, affecting 61% of participants, and the study found that AE rates were higher in the Spring, Fall, and Winter compared to Summer, indicating that seasonal factors may influence the frequency of AEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rates of adverse and serious adverse events in children with cystic fibrosis. Pittman, JE., Khan, U., Laguna, TA., et al.[2022]

This trial aims to evaluate the safety and tolerability of bacteriophage therapy in children with cystic fibrosis (CF) who are infected with Pseudomonas aeruginosa, involving up to 10 participants over a maximum of 36 months.

Bacteriophages will be administered via endo-bronchial delivery and nebulization, alongside standard CF treatments, with safety monitored through specific criteria such as fever and spirometry changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-arm, open-labelled, safety and tolerability of intrabronchial and nebulised bacteriophage treatment in children with cystic fibrosis and Pseudomonas aeruginosa. Singh, J., Fitzgerald, DA., Jaffe, A., et al.[2023]

Two cystic fibrosis patients with pan-drug-resistant Pseudomonas aeruginosa were successfully treated using bacteriophages, a novel therapeutic strategy that could offer new hope for difficult-to-treat infections.

The cases emphasize the urgent need for further research and pediatric clinical trials to explore the efficacy and safety of bacteriophage therapy in cystic fibrosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacteriophage Therapy for Pan-Drug-Resistant Pseudomonas aeruginosa in Two Persons With Cystic Fibrosis. Hahn, A., Sami, I., Chaney, H., et al.[2023]

In a Phase I/II clinical trial involving 24 patients with chronic otitis caused by antibiotic-resistant Pseudomonas aeruginosa, the bacteriophage preparation Biophage-PA demonstrated significant efficacy in reducing bacterial counts and improving clinical indicators compared to a placebo.

No adverse events related to the treatment were reported, indicating that Biophage-PA is a safe option for treating chronic otitis infections resistant to conventional antibiotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy. Wright, A., Hawkins, CH., Anggård, EE., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12092284/

Personalized inhaled bacteriophage therapy for treatment ... In addition, an improvement of 6% (median) and 8% (mean) predicted FEV1 was observed 21–35 days after phage therapy (P = 0.004, Wilcoxon signed- ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05453578

Study Details | NCT05453578 | A Phase 1b/2 Trial of the ... This clinical trial is designed to assess the safety and microbiological activity of bacteriophage product Walter Reed Army Institute of Research- PAM-Cystic ...

3. health.ucsd.edu health.ucsd.edu/news/press-releases/2022-10-11-phage-trial-to-treat-cf-patients-with-multi-drug-resistant-bacterial-infections/

Phage Trial to Treat CF Patients with Multi-Drug Resistant ... In 2020, IPATH researchers published data from 10 cases of intravenous bacteriophage therapy to treat multidrug-resistant bacterial infections, ...

4. withpower.com withpower.com/trial/phase-2-pseudomonas-infections-6-2022-a639e

IV Bacteriophage Therapy for Cystic Fibrosis Research shows that bacteriophage therapy, which is part of the WRAIR-PAM-CF1 treatment, has been successfully used to treat infections in cystic fibrosis ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1526054223000453

A systematic review on the use of bacteriophage in treating ... Evidence suggests that bacteriophage therapy may be a promising treatment option for CF-related infections caused by P. aeruginosa and S. aureus. However, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9795609/

Safety and microbiological activity of phage therapy in ... Safety and microbiological activity of phage therapy in persons with cystic fibrosis ... WRAIR-PAM-CF1 is a cocktail of four phages in a 1:1:1:1 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05453578

Study Details | NCT05453578 | A Phase 1b/2 Trial of the ... This clinical trial is designed to assess the safety and microbiological activity of bacteriophage product Walter Reed Army Institute of Research- PAM-Cystic ...

8. clinicaltrialsarena.com clinicaltrialsarena.com/news/adaptive-phage-cystic-fibrosis/

Adaptive Phage begins subject dosing in cystic fibrosis ... The trial will assess the safety and microbiological activity of WRAIR-PAM-CF1 in adult cystic fibrosis patients. January 13, 2023. Share.

9. niaid.nih.gov niaid.nih.gov/news-events/nih-supported-clinical-trial-phage-therapy-cystic-fibrosis-begins

NIH-Supported Clinical Trial of Phage Therapy for Cystic ... The trial is evaluating whether the bacteriophage, or “phage,” therapy is safe and able to reduce the amount of bacteria in the lungs of volunteers.

10. journals.asm.org journals.asm.org/doi/10.1128/mra.00275-25

Genome sequences of two phages active against cystic ... Our team has developed a four-phage cocktail WRAIR-PAM-CF1 active against P. aeruginosa isolates from cystic fibrosis patients currently ...