A First in Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Immunogenicity of PMG1015

NCT05022771 | Completed Phase 1

• 1 other identifier: PMG1015-AUS-101
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1A, first in human, randomized, double-blinded, placebo-controlled, dose escalation study of PMG1015 in healthy adult volunteers. PMG1015 is a monoclonal antibody, being developed as a novel therapeutic treatment for patients with Idiopathic Pulmonary fibrosis (IPF). This study aims to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of PMG1015 after Single ascending doses (SAD).

Conditions

Idiopathic Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (9)

• The incidence of Treatment-emergent adverse events (TEAEs)

  An Adverse Event (AE) is any event, side-effect or any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs are AEs that occur following the start of treatment.

  Day 1-Day 85

• The severity of Treatment-emergent adverse events (TEAEs)

  TEAEs are AEs that occur following the start of treatment.

  Day 1-Day 85

• The incidence of Serious adverse events (SAEs)

  A serious adverse event (SAE) is defined as an AE occurring during any study phase and at any dose of IP (active or placebo) that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect.

  Day 1-Day 85

• The severity of Serious adverse events (SAEs)

  A serious adverse event (SAE) is defined as an AE occurring during any study phase and at any dose of IP (active or placebo) that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect.

  Day 1- Day 85

• Number of participants with abnormally clinical vital signs

  Vital signs include pulse rate (PR), blood pressure (BP), respiratory rate (RR) and tympanic temperature (T)

  Day 1- Day 85

• Number of participants with abnormal clinically significant 12-lead electrocardiogram (ECG) parameters

  All ECG tracings will be reviewed by the PI or designee and assessed for clinical significance.

  Day 1-Day 85.

• Number of participants with abnormal clinically significant clinical laboratory results

  Clinical laboratory test include hematology, coagulation, biochemistry, and urinalysis.

  Day 1- Day 85

• MTD of PMG1015 in healthy participants

  Maximum tolerated dose of PMG1015 in healthy participants

  Day 1- Day 85

• Number of patients with abnormal clinically significant results from physical examination

  Complete physical examination include, general appearance, head, eyes, ears, nose, throat, dentition, thyroid, chest (heart, lungs), abdomen, skin, neurological, extremities, back, neck, musculoskeletal, and lymph nodes.

  Day 1-Day 85

Secondary Outcomes (10)

• Area under the serum-concentration time curve (AUC) from time zero (from the start of infusion time) to the last time point with measurable analyte concentration (AUC0-t)

  Day 1-Day 85.

• AUC from time zero to infinity (AUC0-∞)

  Day 1-Day 85.

• To determine %AUCexp

  Day 1-Day 85.

• To determine Cmax

  Day 1-Day 85.

• To determine Tmax, derived from serum concentration of each dose of PMG1015

  Day 1-Day 85.

Study Arms (7)

Single Ascending Doses Cohort 1a

EXPERIMENTAL

Subjects will receive either Dose level 1 of PMG1015 or Placebo

Drug: PMG1015 Dose 1; Drug: Placebo

Single Ascending Doses Cohort 1b

EXPERIMENTAL

Subjects will receive either Dose level 2 of PMG1015 or Placebo

Drug: PMG1015 Dose 2; Drug: Placebo

Single Ascending Doses Cohort 1c

EXPERIMENTAL

Subjects will receive either Dose level 3 of PMG1015 or Placebo

Drug: PMG1015 Dose 3; Drug: Placebo

Single Ascending Doses Cohort 1d

EXPERIMENTAL

Subjects will receive either Dose level 4 of PMG1015 or Placebo

Drug: PMG1015 Dose 4; Drug: Placebo

Single Ascending Doses Cohort 1e

EXPERIMENTAL

Subjects will receive either Dose level 5 of PMG1015 or Placebo

Drug: PMG1015 Dose 5; Drug: Placebo

Single Ascending Doses Cohort 1f

EXPERIMENTAL

Subjects will receive either Dose level 6 of PMG1015 or Placebo

Drug: PMG1015 Dose 6; Drug: Placebo

Single Ascending Doses Cohort 1g

EXPERIMENTAL

Subjects will receive either Dose level 7 of PMG1015 or Placebo

Drug: Placebo; Drug: PMG1015 Dose 7

Interventions

PMG1015 Dose 1 DRUG

Dose level 1 of PMG1015

Also known as: PMG1015

Single Ascending Doses Cohort 1a

PMG1015 Dose 2 DRUG

Dose level 2 of PMG1015

Also known as: PMG1015

Single Ascending Doses Cohort 1b

PMG1015 Dose 3 DRUG

Dose level 3 of PMG1015

Also known as: PMG1015

Single Ascending Doses Cohort 1c

PMG1015 Dose 4 DRUG

Dose level 4 of PMG1015

Also known as: PMG1015

Single Ascending Doses Cohort 1d

PMG1015 Dose 5 DRUG

Dose level 5 of PMG1015

Also known as: PMG1015

Single Ascending Doses Cohort 1e

PMG1015 Dose 6 DRUG

Dose level 6 of PMG1015

Also known as: PMG1015

Single Ascending Doses Cohort 1f

Placebo DRUG

Placebo to match

Single Ascending Doses Cohort 1a; Single Ascending Doses Cohort 1b; Single Ascending Doses Cohort 1c; Single Ascending Doses Cohort 1d; Single Ascending Doses Cohort 1e; Single Ascending Doses Cohort 1f; Single Ascending Doses Cohort 1g

PMG1015 Dose 7 DRUG

Dose level 7 of PMG1015

Also known as: PMG1015

Single Ascending Doses Cohort 1g

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male or non-pregnant, non-lactating female volunteers, between 18 and 60 years of age, inclusive at the time of informed consent.
• Body mass index (BMI) between 17.5 and 32.0 kg/m2 (inclusive) and body weight between 50 and 100 kg for males and between 45 and 100 kg for females.
• No clinically significant clinical laboratory values (Hematology, coagulation, biochemistry and urinalysis) at the discretion of the PI.
• Females of child bearing potential must use an acceptable, highly effective double contraception and have a negative pregnancy test at Screening and Day-1.
• Documented evidence of surgical sterilization at least 6 months prior to screening for women or vasectomy at least 90 days prior to screening.
• Women not of child bearing potential must be menopausal for \>/= 12 months.
• Males must not donate sperms for at least 90 days after PMG1015 administration.

You may not qualify if:

• History or evidence of clinically significant condition, including but not limited to any cardiovascular, gastrointestinal, endocrinologic, hematologic, psychiatric, renal disease, musculoskeletal, infectious, or neurological condition or any chronic medical condition and/or other major disease, as determined by the PI.
• A PR \< 40 or \> 100 beats per minute, mean systolic blood pressure (SBP) \> 140 mmHg, or mean diastolic blood pressure (DBP) \> 95 mmHg .
• A mean corrected QT interval using Fridericia's formula (QTcF) interval at Screening \> 450 ms in males and \> 470 ms in females. If the mean QTcF exceeds these limits, one additional triplicate ECG will be performed.
• Any clinically significant abnormalities in rhythm, conduction, or morphology of the resting ECG and any abnormalities in the 12-lead ECG that, in the judgment of the PI, may interfere with the interpretation of QTc-interval changes, including abnormal ST-T wave morphology or left ventricular hypertrophy.
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or creatinine \> 1.5 × the upper limit of the normal range (ULN) or total bilirubin or lymphocyte counts \> ULN.
• Participants with a positive toxicology screening panel or alcohol breath test on Screening/Day-1.
• Participants with a history of substance abuse or dependency or history of recreational IV drug use over the last 2 years.
• Plasma donation/Blood donation or significant blood loss within 60 days prior to the first IP administration.
• Use of any IP (including other investigational mAb products) or investigational medical device within 30 days prior to Screening or 5 half-lives of the product (whichever is the longest) or participation in more than 4 investigational drug studies within 1 year prior to screening.
• Major surgery (general anesthetic) within 3 months or minor surgery (local anesthetic) within 1 month prior to IP administration, or planned surgery during the study period, which is determined by the PI to be clinically relevant.
• Fever or symptomatic bacterial or viral infection.
• Participants who have received live vaccines or attenuated vaccines within 1 month before dosing.
• Participants with any active malignancy or history of malignancy within 5 years prior to enrolment.
• Use of any other prescription medications.
• History of anaphylaxis, allergic reactions to the excipients of IP, asthma.

Sponsors & Collaborators

• Pulmongene Ltd.: lead

Study Sites (1)

Q-Pharm Pty Ltd, Clive Berghofer Cancer Research Centre

Herston, Queensland, 4006, Australia

Location

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Richard Friend

  Nucleus Network

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 20, 2021
• First Posted: August 26, 2021
• Study Start: October 14, 2021
• Primary Completion: August 18, 2022
• Study Completion: August 18, 2022
• Last Updated: January 31, 2023

Record last verified: 2023-01

Locations

AU (1)