A 2-Part First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of CMTX-101

NCT05629741 | Terminated Phase 1 FDA Drug

• 1 other identifier: CMTX101-P1-CT001
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 8

Brief Summary

CMTX-101 is a bacterial biofilm disrupting monoclonal antibody being developed as an adjunct therapy with standard of care antibiotics. The goal of this clinical trial is to assess the safety and tolerability of CMTX-101 in healthy volunteers followed by a similar assessment in patients with suspected or confirmed community acquired bacterial pneumonia of moderate severity. The main questions the study aims to answer are:

• Are single ascending doses of a CMTX-101 intravenous (IV) infusion safe and tolerated
• What is the pharmacokinetic (PK) profile of single-ascending doses CMTX 101
• Do single ascending doses of CMTX 101 induce development of anti-drug antibodies (ADA) and neutralizing antibodies (Nabs) Exploratory efficacy biomarkers will also be measured in the patient part of the study. Participants will be administered a single IV infusion of CMTX-101 over a 60-minute period; patients will receive the infusion after starting standard of care antibiotics.

Conditions

Community-acquired Pneumonia; Bacterial Pneumonia

Outcome Measures

Primary Outcomes (6)

• Number and % of healthy subjects experiencing Adverse Events following ascending doses of a single CMTX-101 IV infusion

  Primary objective of Part 1

  Cohorts 1 and 2: Day 1 to Day 29. Cohorts 3 and 4: Day 1 to Day 100.

• Number and % of healthy subjects experiencing Serious Adverse Events following ascending doses of a single CMTX-101 IV infusion

  Primary objective of Part 1

  Cohorts 1 and 2: Day 1 to Day 29. Cohorts 3 and 4: Day 1 to Day 100.

• Number and % of healthy subjects experiencing Solicited Adverse Events following ascending doses of a single CMTX-101 IV infusion

  Primary objective of Part 1

  Cohorts 1 and 2: Day 1 to Day 29. Cohorts 3 and 4: Day 1 to Day 100.

• Number and % of hospitalized subjects with suspected or confirmed CABP of moderate severity experiencing Adverse Events following dosing of a single CMTX-101 IV infusion

  Primary objective of Part 2

  Day 1 to Day 35

• Number and % of hospitalized subjects with suspected or confirmed CABP of moderate severity experiencing Serious Adverse Events following dosing of a single CMTX-101 IV infusion

  Primary objective of Part 2

  Day 1 to Day 35

• Number and % of hospitalized subjects with suspected or confirmed CABP of moderate severity experiencing Solicited Adverse Events following dosing of a single CMTX-101 IV infusion

  Primary objective of Part 2

  Day 1 to Day 35

Secondary Outcomes (18)

• Assess the CMax - Observed maximum plasma concentration determined by ELISA following ascending doses of a single CMTX-101 IV infusion in healthy subjects

  Cohorts 1 and 2: Day 1 to Day 29. Cohorts 3 and 4: Day 1 to Day 100.

• Assess the TMax - Time to reach maximum plasma concentration determined by ELISA following ascending doses of a single CMTX-101 IV infusion in healthy subjects

  Cohorts 1 and 2: Day 1 to Day 29. Cohorts 3 and 4: Day 1 to Day 100.

• Assess the AUC0-last Area under the concentration time curve following ascending doses of a single CMTX-101 IV infusion in healthy subjects

  Cohorts 1 and 2: Day 1 to Day 29. Cohorts 3 and 4: Day 1 to Day 100.

• Assess the AUC0-∞ Area under the concentration time curve from zero to infinite time following ascending doses of a single CMTX-101 IV infusion in healthy subjects

  Cohorts 1 and 2: Day 1 to Day 29. Cohorts 3 and 4: Day 1 to Day 100.

• Assess the Terminal phase elimination rate determined by ELISA following ascending doses of a single CMTX-101 IV infusion in healthy subjects

  Cohorts 1 and 2: Day 1 to Day 29. Cohorts 3 and 4: Day 1 to Day 100.

Study Arms (5)

CMTX-101 2.5 mg/kg

EXPERIMENTAL

CMTX-101 will be administered as a single IV infusion over 60 minutes.

Drug: CMTX-101

CMTX-101 5 mg/kg

EXPERIMENTAL

CMTX-101 will be administered as a single IV infusion over 60 minutes.

Drug: CMTX-101

CMTX-101 15 mg/kg

EXPERIMENTAL

CMTX-101 will be administered as a single IV infusion over 60 minutes.

Drug: CMTX-101

CMTX-101 30 mg/kg

EXPERIMENTAL

CMTX-101 will be administered as a single IV infusion over 60 minutes.

Drug: CMTX-101

CMTX-101 0 mg/kg

PLACEBO COMPARATOR

Placebo will be administered as a single IV infusion over 60 minutes

Drug: Placebo

Interventions

CMTX-101 DRUG

Administered as specified in the treatment arm

CMTX-101 15 mg/kg; CMTX-101 2.5 mg/kg; CMTX-101 30 mg/kg; CMTX-101 5 mg/kg

Placebo DRUG

Administered as specified in the treatment arm

CMTX-101 0 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is ≥ 18 years of age at Screening;
• Is able to provide written informed consent;
• If a female subject of non-childbearing potential, is either surgically sterile (i.e., has had a hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy at least 26 weeks before Screening) or post-menopausal, defined as spontaneous amenorrhea for at least 2 years, with a follicle-stimulating hormone in the post-menopausal range obtained during Screening;
• Contraceptive requirements: If a female subject of childbearing potential (i.e., ovulating, pre-menopausal, and not surgically sterile) with a male partner or a male subject with a female partner, must use a medically accepted contraceptive regimen during her/his participation in the study and for 4 months after the last infusion of study drug. Medically accepted contraceptive methods are defined as those with 90% or greater efficacy;
• Acceptable methods of contraception for male subjects include the following:
• Condoms with spermicide;
• Surgical sterilization of subject (i.e., vasectomy) at least 26 weeks before Screening; or
• Sexual abstinence (i.e., refraining from heterosexual intercourse), if the preferred and usual lifestyle of the subject.
• Acceptable methods of contraception for female subjects include the following:
• Bilateral tubal ligation, completed at least 12 weeks prior to Screening;
• Intrauterine device used for at least 12 weeks prior to Screening;
• Hormonal contraception (oral, implant, injection, ring, or patch) for at least 12 weeks prior to Screening;
• Diaphragm used in combination with spermicide; or
• Sexual abstinence (i.e., refraining from heterosexual intercourse), if the preferred and usual lifestyle of the subject.
• If a male subject, must agree to abstain from sperm donation through 4 months after infusion of the last dose of study drug;

You may not qualify if:

• Has a history or evidence of systemic autoimmune disease;
• Has received immunoglobulin or blood products within 120 days prior to Screening;
• Has a known history or evidence of HIV infection;
• Has a known history or evidence of chronic hepatitis B defined as persistent hepatitis B surface antigen for \>6 months, or has an active hepatitis C virus (HCV) infection, defined as positive HCV RNA; Note: Patients with positive HCV antibodies and negative HCV RNA will be permitted.
• Has a positive test for drugs of abuse at Screening (both parts) or Day -1 (Part 1);
• Is participating, plans to participate during the study period, or has participated within the last 30 days prior to Screening in any other investigational study;
• Has received an investigational drug or live vaccine within 30 days or 5 half-lives of the investigational compound, whichever is longer, prior to Screening;
• Is currently pregnant or lactating/nursing;
• Has a history or evidence of an allergic reaction that, in the opinion of the Investigator, may compromise the safety of the subject;
• Has a known or suspected hypersensitivity to CMTX-101 or its excipients;
• Has a history or evidence of any other acute or chronic disease that, in the opinion of the Investigator, may interfere with the evaluation of the safety or immunogenicity of the drug or compromise the safety of the subject;
• Has an oral temperature ≥37.5°C (≥99.5°F) at Screening or Day -1;
• Has an abnormal WBC count, hemoglobin, or platelet count (i.e., \>1.5 x upper limit of normal \[ULN\] or \>0.5 x below the lower limit of normal (LLN) per the local laboratory or deemed to be clinically significant per the Investigator) at Screening or Day -1;
• Has an abnormally elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase (ALP), blood urea nitrogen, or creatinine (i.e., \>1.5 x ULN per the local laboratory) at Screening or Day -1;
• Has an abnormal urinalysis at Screening or Day -1 that, in the opinion of the Investigator, is clinically significant;

Sponsors & Collaborators

• Clarametyx Biosciences, Inc.: lead

Study Sites (8)

Augusta University Health

Augusta, Georgia, 30912, United States

Location

Snake River Research, PLLC

Idaho Falls, Idaho, 83404, United States

Location

University of Louisville

Louisville, Kentucky, 40292, United States

Location

Wayne State University

Detroit, Michigan, 48202, United States

Location

Buffalo VA Medical Center

Buffalo, New York, 14215, United States

Location

Medpace Clinical Pharmacology Unit

Cincinnati, Ohio, 45227, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Virginia School of Medicine

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Community-Acquired Pneumonia; Pneumonia, Bacterial

Condition Hierarchy (Ancestors)

Community-Acquired Infections; Infections; Pneumonia; Respiratory Tract Infections; Respiratory Tract Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Lung Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2022
• First Posted: November 29, 2022
• Study Start: November 14, 2022
• Primary Completion: August 2, 2024
• Study Completion: August 2, 2024
• Last Updated: October 21, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)