Summary

Eligibility
for people ages 18-99 (full criteria)
Location
at La Jolla, California and other locations
Dates
study started
estimated completion

Description

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 and diagnosed with Cystic Fibrosis (CF), and residing in the United States. This clinical trial is designed to assess the safety and microbiologic activity of bacteriophage product WRAIR_PAM-CF1, directed at Pseudomonas aeruginosa in clinically stable CF individuals. WRAIR_PAM-CF1 is a 4 component anti-pseudomonal bacteriophage containing between >/= 4 x 107 and >/= 4 x 109 Plaque Forming Units (PFU) in the target dose. Enrollment will occur at up to 20 clinical research 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 107 PFU, 4 x 108 PFU, and 4 x 109 PFU; total of 6 sentinel subjects), followed by a 96-hour observation period. Stage 2a will proceed if no serious adverse events (SAEs) related to the study product occur during the observation period of stage 1; 32 subjects will be enrolled into one of 4 arms (placebo IV, 4 x 107 PFU, 4 x 108 PFU, and 4 x 109 PFU) in a 1:1:1:1 allocation. An interim analysis after all subjects have completed follow up visit 5 on Day 30 will be performed to select an IV bacteriophage dose with the most favorable safety and microbiologic 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.

Official Title

A Phase 1b/2, Multi-Centered, Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Microbiological Activity of a Single Dose of Bacteriophage Therapy in Cystic Fibrosis Subjects Colonized With Pseudomonas Aeruginosa

Details

This is a phase 1b/2, multicenter, randomized placebo-controlled double-blind study of a single dose of intravenous (IV) bacteriophage in males and non-pregnant females, at least 18 years old and diagnosed with Cystic Fibrosis (CF), and residing in the United States. This clinical trial is designed to assess the safety and microbiologic activity of bacteriophage product WRAIR_PAM-CF1, directed at Pseudomonas aeruginosa in clinically stable CF individuals. WRAIR_PAM-CF1 is a 4 component anti-pseudomonal bacteriophage containing between >/= 4 x 107 and >/= 4 x 109 Plaque Forming Units (PFU) in the target dose. Enrollment will occur at up to 20 clinical research sites in the United States. In stage 1, two sentinel subjects will be assigned to each of the three dosing arms receiving a single dosage of the IV bacteriophage therapy (4 x 107 PFU, 4 x 108 PFU, and 4 x 109 PFU; total of 6 sentinel subjects), followed by a 96-hour observation period to assess safety of study product. Stage 2a will proceed if no serious adverse events (SAEs) related to the study product occur during the observation period of stage 1; 32 subjects will be enrolled into one of 4 arms (placebo IV, 4 x 107 PFU, 4 x 108 PFU, and 4 x 109 PFU) in a 1:1:1:1 allocation. An interim analysis after all subjects have completed follow up visit 5 on Day 30 will be performed to select an IV bacteriophage dose with the most favorable safety and microbiologic 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. The primary objectives of this study are to 1) describe the safety of a single dose of IV bacteriophage therapy in clinically stable CF subjects with P. aeruginosa in expectorated sputum; 2) describe the microbiological activity of a single dose of IV bacteriophage therapy in clinically stable adult CF subjects with P. aeruginosa in expectorated sputum; 3) describe the benefit to risk profile of a single dose of IV bacteriophage therapy in clinically stable CF subjects with P. aeruginosa in expectorated sputum.

Keywords

Bacterial Disease Carrier Cystic Fibrosis Bacteriophage therapy Microbiological Activity Pseudomonas aeruginosa Safety Pseudomonas Infections Bacterial Infections Fibrosis WRAIR_PAM-CF1

Eligibility

You can join if…

Open to people ages 18-99

Subjects must meet all the inclusion criteria to be eligible to participate in the study:

  1. Adult (>/= 18 years) at the time of screening.
  2. Confirmed CF diagnosis based on a compatible clinical syndrome confirmed by either an abnormal sweat chloride testing or two CFTR gene variations.*

*Can be obtained from documentation in medical records; actual test results not necessary.

  1. Readily 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.*

**Determined by investigator or their designee judgement. Approaches for obtaining sputum may include, but are not limited to, inhaled hypertonic saline (e.g. 3%, 7%, or 10%), inhaled hypertonic bicarbonate, inhaled mannitol, or spontaneously expectorated sputum. The same approach should be used for all sputum collections for a given subject, refer to the MOP for further details.

    1. aeruginosa (regardless of Colony Forming Units (CFU)/mL) isolated from a sputum, throat culture, or other respiratory specimen in the past 12 months.
  1. Confirmed P. aeruginosa isolation from a sample of expectorated sputum at the screening visit.
  2. Capable of providing informed consent.
  3. Capable and willing to complete all study visits and perform all procedures required by this protocol.

You CAN'T join if...

Subjects who meet any of the exclusion criteria will not be enrolled in the study:

  1. Body weight < 30 kg.
  2. Forced Expiratory Volume 1< 20% of predicted value at screening, using the Hankinson equations.25
  3. Elevated LFTs obtained at screening.*

*a. Alanine aminotransferase (ALT) > 5 x the upper limit of normal (ULN) or aspartate transaminase (AST) > 5 x ULN or total bilirubin > 3 x ULN, OR b. Total bilirubin > 1.5 x ULN combined with either ALT > 3 x ULN or AST > 3 x ULN. ULN reflect local laboratory ranges.

  1. Acute clinical illness requiring a new (oral, parenteral), or inhaled antibiotic(s) = 30 days prior to the baseline visit.*

*Does not include chronic suppressive medications or cyclic dosing medications such as inhaled antibiotics.

  1. 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.*

*A female is considered of childbearing potential unless postmenopausal, or surgically sterilized and at least 3 months has passed since sterilization procedure.

  1. Female surgical sterilization procedures include tubal ligation, bilateral salpingectomy, hysterectomy, or bilateral oophorectomy
  2. 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.
  3. 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).
  4. Active treatment of any nontuberculous mycobacteria or fungal organisms </=30 days prior to baseline. Chronic treatment for suppression of fungal populations is allowable.
  5. Anticipated need to change chronic antibiotic regimens during the study period.*

*Subjects on cyclic dosing medications such as inhaled antibiotics, must be able and express willingness to keep the therapies at the time of screening constant for the duration of the follow-up period (approximately 30 days). Subjects on chronic suppressive antimicrobial therapy must be able and express willingness to stay on the therapies for the duration of their follow-up period. This includes chronic azithromycin therapy.

  1. Known allergy to any component of the study product.
  2. Any significant finding that, in the opinion of the investigator, would make it unsafe for the subject to participate in this study.
  3. . Enrolled in a clinical trial within </=30 days of the baseline/dosing visit, or participating in a clinical trial while enrolled in this clinical trial (inclusive of prophylactic vaccine trials).
  4. . Currently or previously enrolled in this trial.

Locations

  • University of California San Diego School of Medicine - Pathology
    La Jolla California 92037 United States
  • Stanford University School of Medicine
    Stanford California 94305-2200 United States

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
ID
NCT05453578
Phase
Phase 1/2 research study
Study Type
Interventional
Participants
Expecting 72 study participants
Last Updated