Clinical trial NCT06159725: A Study To Evaluate The Safety Of CMTX-101 In People With Cystic Fibrosis
Official title: A Phase 1b/2a Study To Evaluate The Safety Of CMTX-101 In Combination With Inhaled Antibiotics In People With Cystic Fibrosis Chronically Infected With Pseudomonas Aeruginosa
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Persistent Infection
Cystic Fibrosis
Keywords: Pseudamonas auriginosa
Lead sponsor: Clarametyx Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2023-12-07
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1 is a single-group, unblinded study Part 2 is a randomized, parallel-group, placebo-controlled, double-blind study.
Primary purpose: TREATMENT

Brief summary: CMTX-101 is a bacterial biofilm disrupting monoclonal antibody being developed as an adjunctive therapy to standard of care antibiotics. The goal of this clinical trial is to assess the safety and tolerability of CMTX-101 in people with cystic fibrosis (pwCF).

The main questions the study aims to answer are:

* Are single doses of CMTX-101 IV infusion safe and tolerated
* What is the pharmacokinetic (PK) profile of single doses of CMTX-101
* Do single doses of CMTX-101 induce development of anti-drug antibodies (ADA) and neutralizing antibodies (Nabs)


Eligibility criteria: Inclusion Criteria:

1. Adults ≥18 years of age at the time of screening.
2. If enrolled in the CFF Patient Registry, must provide registry information.
3. Confirmed CF diagnosis based on current CF Foundation (CFF)-sponsored guidelines.
4. For participants on modulator therapy, they must be on a stable dose of modulator therapy for at least 3 months.
5. Willing and capable of providing induced sputum for evaluation at defined study timepoints.
6. Positive P. aeruginosa growth of ≥104 CFU/gram from a sample of induced sputum at the screening visit.
7. FEV1 ≥50% (Part1) or ≥35% (Part 2) of predicted normal value at screening.
8. Currently receiving inhaled antibiotic therapy, either tobramycin or aztreonam alone, or as part of CAT. At least one 28-day cycle completed within 8 weeks prior to screening visit.
9. Women of childbearing potential (WOCBP) 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 study and for 4 months after the last infusion of study drug. A female participant is considered of childbearing potential unless postmenopausal or surgically sterilized and at least 3 months has passed since sterilization procedure. Female surgical sterilization procedures include tubal ligation, bilateral salpingectomy, hysterectomy, or bilateral oophorectomy. A female participant is considered postmenopausal if she has had spontaneous amenorrhea for at least 2 years with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms).

   • 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).
10. Male participants with a female partner must use a medically accepted contraceptive regimen during his participation in the study and for 4 months after study drug infusion.

    • Acceptable methods of contraception for male participants include condoms with spermicide, surgical sterilization of the participant (i.e., vasectomy) at least 26 weeks before screening, or sexual abstinence (i.e., refraining from heterosexual intercourse) if that is the preferred and usual lifestyle of the participant.

    - Males with infertility documentation are not required to use contraception.
11. Male participants must agree to abstain from sperm donation through 4 months after study drug administration.
12. Capable of providing informed consent.
13. Capable and willing to complete all study visits and perform all procedures required by the protocol.

Exclusion Criteria:

1. Body mass index (BMI) \<14 at screening and baseline.
2. Has a known history or evidence of human immunodeficiency virus (HIV) infection or chronic hepatitis B screening.
3. Tests positive for hepatitis C virus (HCV) RNA at screening.
4. Pulmonary exacerbation within 28 days of baseline.
5. Requirement for continuous (24 hour/day) oxygen supplementation; periodic use is permitted.
6. Participation in smoking or vaping activity in the last 6 months.
7. History of, or planned, organ transplantation.
8. Elevated liver function tests obtained at screening.

   1. ALT \>5 × ULN or AST \>5 × ULN, or
   2. Total bilirubin \>3 × ULN or Total bilirubin \>1.5 × ULN combined with either ALT \>3 × ULN or AST \>3 × ULN. ULN reflects local laboratory ranges.
9. Greater than 5 ml of hemoptysis on one occasion or \>30 mL of hemoptysis in a 24-hour period within 28 days of baseline.
10. Infection with other more pathogenic organisms such as Mycobacterium abscessus or Burkholderia spp., where the investigator feels that the participant either is not or will not remain clinically stable throughout the duration of the study.
11. 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.
12. Women who are pregnant, planning to become pregnant during the study period or for 4 months following last infusion of study drug, or breastfeeding.
13. Active treatment of any mycobacterial or fungal organisms ≤30 days prior to baseline visit. Chronic treatment for suppression of fungal populations is allowable.
14. Anticipated need to change chronic (either inhaled or oral) antibiotic regimens during the study period. Participants must agree to maintain their current chronic antibiotic regimen from the screening visit for the duration of the follow-up period (approximately 30 days).
15. Known allergy to any component of the study drug.
16. Participant with an estimated glomerular filtration rate \<60 mL/min/1.73 m2.
17. Any significant finding that, in the opinion of the investigator, would make it unsafe for the participant to participate in this study or would not be in the best interest of the participant.
18. Enrolled in an interventional clinical study within ≤60 days of the baseline visit, or participating in a clinical study while enrolled in this clinical study (inclusive of vaccine studies).
19. Currently or previously enrolled in this study.

Primary outcomes:
measure: Number and % of participants experiencing adverse events following a single IV infusion of CMTX-101
timeFrame: Day 1 to Day 28
measure: Number and % of participants experiencing serious adverse events following a single IV infusion of CMTX-101
timeFrame: Day 1 to Day 28
Secondary outcomes:
measure: Assess the CMax - observed maximum plasma concentration determined by ELISA following a single IV infustion of CMTX-101
timeFrame: Day 1 to Day 35
measure: Assess the TMax - time to reach maximum concentration curve following a single IV infusion of CMTX-101
timeFrame: Day 1 to Day 35
measure: Assess the AUC0-∞ Area under the concentration time curve from zero to infinite time following a single IV infusion of CMTX-101
timeFrame: Day 1 to Day 35
measure: Assess the Terminal phase elimination rate determined by ELISA following a single IV infusion of CMTX-101
timeFrame: Day 1 to Day 35
measure: Assess the Terminal elimination half- determined by ELISA following a single IV infusion of CMTX-101
timeFrame: Day 1 to Day 35
measure: Assess the Apparent total body clearance (CL/F) determined by ELISA following a single IV infusion of CMTX-101
timeFrame: Day 1 to Day 35
measure: Assess the Apparent volume distribution (Vx/F) determined by ELISA following a single IV infustion of CMTX-101
timeFrame: Day 1 to Day 35
measure: Evaluate the immunogenicity of CMTX-101 as measured by anti-drug antibodies (ADA) determined by the electrochemiluminescence assay following a single IV infustion of CMTX-101
timeFrame: Day 1 to Day 35
measure: Assess the apparent reduction in pulmonary P. auriginosa burden as measured by quantitative microbial culture of sputum
timeFrame: Day 1 to Day 28
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham
state: Alabama
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Orlando
country: United States
facility: Central Florida Pulmonary Group, PA
state: Florida
city: Boise
country: United States
facility: St Luke's Sleep Medicine and Research Center
state: Idaho
city: Kansas City
country: United States
facility: University of Kansas
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Hawthorne
country: United States
facility: New York Medical College
state: New York
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Hershey
country: United States
facility: PennState Health
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
References: