A Phase 1b/2 Trial of the Safety and Microbiological Activity of Bacteriophage Therapy in Cystic Fibrosis Subjects Colonized With Pseudomonas Aeruginosa

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Jul 7, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called bacteriophage therapy for people with Cystic Fibrosis (CF) who are infected with a bacteria known as Pseudomonas aeruginosa. The trial aims to find out if this treatment is safe and how well it works. It involves giving a single dose of bacteriophage through an intravenous (IV) line to adults aged 18 and older. To be eligible, participants must have a confirmed diagnosis of CF and a recent history of being infected with Pseudomonas aeruginosa. They should also be able to produce a sample of sputum, which is mucus from the lungs.

Participants in the trial will be monitored closely after receiving the treatment to ensure their safety. If everything goes well, the trial will continue to test different doses of the bacteriophage therapy and compare it to a placebo, which is a treatment that doesn’t contain the active medication. The study is being conducted at multiple sites across the United States, and researchers hope to enroll up to 72 participants. It's important for potential participants to discuss with their doctors if they meet the eligibility criteria and understand what involvement in the trial entails.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• 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 Cystic Fibrosis (CF) diagnosis based on a compatible clinical syndrome confirmed by either an abnormal sweat chloride testing or CFTR gene variations.\*
• • \*Can be obtained from documentation in medical records; actual test results not necessary.
• • 3. 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.\*\*
• • \*\*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 is recommended, whenever possible, for all sputum collections for a given subject.
• • 4. Pseudomonas aeruginosa (regardless of Colony Forming Units (CFU)/mL) isolated from a sputum, throat culture, or other respiratory specimen in the past 12 months.
• • 5. Confirmed P. aeruginosa isolation from a sample of expectorated sputum at the Screening Visit.
• • 6. Capable of providing informed consent.
• • 7. Capable and willing to complete all study visits and perform all procedures required by the protocol.
• Exclusion Criteria:
• Subjects who meet any of the exclusion criteria will not be enrolled in the study:
• • 1. Body weight \< 30 kg.
• • 2. Forced Expiratory Volume in 1 second (FEV1) \< 20% of predicted value at screening, using the Hankinson equations.
• • 3. Elevated Elevated liver function tests (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 reflects local laboratory ranges.
• • 4. 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.
• • 5. 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).
• • 6. Active treatment of any mycobacterial or fungal organisms \</=30 days prior to baseline. Chronic treatment for suppression of fungal populations is allowable.
• • 7. 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 (either remain on the therapy or not remain on the therapy) 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.
• • 8. Known allergy to any component of the study product.
• • 9. Any significant finding that, in the opinion of the investigator, would make it unsafe for the subject to participate in this study.
• • 10. 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 vaccine trials).
• • 11. Currently or previously enrolled in this trial.