A Phase 1b/2 Trial of the Safety and Microbiological Activity of Bacteriophage Therapy in Cystic … (NCT05453578) | Clinical Trial Compass
CompletedPhase 1/2
A Phase 1b/2 Trial of the Safety and Microbiological Activity of Bacteriophage Therapy in Cystic Fibrosis Subjects Colonized With Pseudomonas Aeruginosa
United States72 participantsStarted 2022-10-03
Plain-language summary
This is a phase 1b/2 study of a single dose of intravenous (IV) bacteriophage in males and non-pregnant females, at least 18 years old, diagnosed with Cystic Fibrosis (CF). This clinical trial is designed to assess the safety and microbiological activity of bacteriophage product Walter Reed Army Institute of Research- PAM-Cystic Fibrosis1 (WRAIR-PAM-CF1), directed at Pseudomonas aeruginosa in clinically stable CF individuals chronically colonized with P. aeruginosa. WRAIR-PAM-CF1 is a 4 component anti-pseudomonal bacteriophage mixture containing between 4 x 10\^7 and 4 x 10\^9 Plaque Forming Units (PFU) of bacteriophage. Enrollment will occur at up to 20 clinical sites in the United States. In stage 1, two eligible subjects will be assigned to each of the three dosing arms receiving a single dosage of the IV bacteriophage therapy (4 x 10\^7 PFU, 4 x 10\^8 PFU, and 4 x 10\^9 PFU; total of 6 sentinel subjects), followed by 30 plus or minus 7 days observation period. If no Serious Adverse Events (SAEs)(related to the study product) are identified during the 96 hours after bacteriophage administration for all Sentinel Subjects in Stage 1, the study will proceed to Stage 2. In Stage 2a, 32 subjects will be enrolled into one of 4 arms (placebo IV, 4 x 10\^7 PFU, 4 x 10\^8 PFU, and 4 x 10\^9 PFU) in a 1:1:1:1 allocation. An interim analysis will be performed after all subjects have completed follow up visit 5 on Day 8+3 to select the IV bacteriophage dose with the most favorable safety and microbiological activity profile. During Stage 2b, subjects will be randomized into the bacteriophage (dose selected based on Interim Analysis following Stage 2a) or placebo arm. The final sample size is expected to be up to 72 subjects total with up to 25 subjects in the placebo arm and up to 25 subjects in the Stage 2b bacteriophage dose.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. Adult (\>/= 18 years) at the time of screening.
✓. Confirmed Cystic Fibrosis (CF) diagnosis based on a compatible clinical syndrome confirmed by either an abnormal sweat chloride testing or CFTR gene variations.\*
✓. Likely able to produce at least 2 mL of sputum during a 30-minute sputum collection following a hypertonic saline treatment or other approach to increase sputum production.\*\*
✓. Pseudomonas aeruginosa (regardless of Colony Forming Units (CFU)/mL) isolated from a sputum, throat culture, or other respiratory specimen in the past 12 months.
✓. Confirmed P. aeruginosa isolation from a sample of expectorated sputum at the Screening Visit.
✓. Capable of providing informed consent.
✓. Capable and willing to complete all study visits and perform all procedures required by the protocol.
Exclusion criteria
✕. Body weight \< 30 kg.
✕
What they're measuring
1
Change from baseline in log10 P. aeruginosa total colony counts in quantitative sputum cultures
Timeframe: Day 1 through Day 30 ± 7
2
Desirability of Outcome Ranking (DOOR)
Timeframe: Day 1 through Day 8 + 3
3
Number of grade 2 or higher treatment-emergent Adverse Events
Timeframe: Day 1 through Day 30 ± 7
Trial details
NCT IDNCT05453578
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
. Forced Expiratory Volume in 1 second (FEV1) \< 20% of predicted value at screening, using the Hankinson equations.
✕. Elevated Elevated liver function tests (LFTs) obtained at screening.\*
✕. Acute clinical illness requiring a new (oral, parenteral), or inhaled antibiotic(s) \</= 30 days prior to the baseline visit.\*
✕. Women who are pregnant, planning to become pregnant during the study period, or breastfeeding.\* \*Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin test during screening and agree to use an effective method of contraception for the duration of the trial.\*
✕. Female surgical sterilization procedures include tubal ligation, bilateral salpingectomy, hysterectomy, or bilateral oophorectomy.
✕. Female is considered postmenopausal if she is \>45 years old and has gone at least 12 months without a spontaneous menstrual period without other known or suspected cause.
✕. Effective methods of contraception include (a) abstinence, (b) partner vasectomy, (c) intrauterine devices, (d) hormonal implants (such as Implanon), or (e) other hormonal methods (birth control pills, injections, patches, vaginal rings).