Clinical trial NCT05022771: A First in Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Immunogenicity of PMG1015
Official title: A Phase 1A, First in Human, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Immunogenicity of PMG1015 in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Idiopathic Pulmonary Fibrosis
Lead sponsor: Pulmongene Ltd.
Sponsor class: INDUSTRY
First posted: 2021-08-26
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Detailed description: Participants will be enrolled and randomized into 1 of 7 cohorts in a double-blind manner.

Eligibility criteria: Inclusion Criteria:

1. Healthy male or non-pregnant, non-lactating female volunteers, between 18 and 60 years of age, inclusive at the time of informed consent.
2. 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.
3. No clinically significant clinical laboratory values (Hematology, coagulation, biochemistry and urinalysis) at the discretion of the PI.
4. Females of child bearing potential must use an acceptable, highly effective double contraception and have a negative pregnancy test at Screening and Day-1.
5. Documented evidence of surgical sterilization at least 6 months prior to screening for women or vasectomy at least 90 days prior to screening.
6. Women not of child bearing potential must be menopausal for \>/= 12 months.
7. Males must not donate sperms for at least 90 days after PMG1015 administration.

Exclusion Criteria:

1. 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.
2. A PR \< 40 or \> 100 beats per minute, mean systolic blood pressure (SBP) \> 140 mmHg, or mean diastolic blood pressure (DBP) \> 95 mmHg .
3. 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.
4. 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.
5. 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.
6. Participants with a positive toxicology screening panel or alcohol breath test on Screening/Day-1.
7. Participants with a history of substance abuse or dependency or history of recreational IV drug use over the last 2 years.
8. Plasma donation/Blood donation or significant blood loss within 60 days prior to the first IP administration.
9. 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.
10. 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.
11. Fever or symptomatic bacterial or viral infection.
12. Participants who have received live vaccines or attenuated vaccines within 1 month before dosing.
13. Participants with any active malignancy or history of malignancy within 5 years prior to enrolment.
14. Use of any other prescription medications.
15. History of anaphylaxis, allergic reactions to the excipients of IP, asthma.
16. Positive blood screen for HIV1/2 antibody, Hepatitis B surface antigen, hepatitis C virus, or syphilis at screening.
17. Participants with an inability to tolerate venous access.
18. Pregnant or lactating at Screening or planning to become pregnant (self or partner) at any time during the study, including the follow-up period.
19. An employee of Pulmongene or Novotech (Australia) Pty Ltd.
20. Participant is unwilling to abstain from alcohol beginning 48 hours prior to admission to the CRU and while resident at the CRU.
21. Any other condition or finding that in the opinion of the PI or designee would put the participant or study conduct at risk.

Primary outcomes:
measure: The incidence of Treatment-emergent adverse events (TEAEs)
timeFrame: Day 1-Day 85
measure: The severity of Treatment-emergent adverse events (TEAEs)
timeFrame: Day 1-Day 85
measure: The incidence of Serious adverse events (SAEs)
timeFrame: Day 1-Day 85
measure: The severity of Serious adverse events (SAEs)
timeFrame: Day 1- Day 85
measure: Number of participants with abnormally clinical vital signs
timeFrame: Day 1- Day 85
measure: Number of participants with abnormal clinically significant 12-lead electrocardiogram (ECG) parameters
timeFrame: Day 1-Day 85.
measure: Number of participants with abnormal clinically significant clinical laboratory results
timeFrame: Day 1- Day 85
measure: MTD of PMG1015 in healthy participants
timeFrame: Day 1- Day 85
measure: Number of patients with abnormal clinically significant results from physical examination
timeFrame: Day 1-Day 85
Secondary outcomes:
measure: 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)
timeFrame: Day 1-Day 85.
measure: AUC from time zero to infinity (AUC0-∞)
timeFrame: Day 1-Day 85.
measure: To determine %AUCexp
timeFrame: Day 1-Day 85.
measure: To determine Cmax
timeFrame: Day 1-Day 85.
measure: To determine Tmax, derived from serum concentration of each dose of PMG1015
timeFrame: Day 1-Day 85.
measure: To determine t1/2
timeFrame: Day 1-Day 85.
measure: Apparent total body clearance (CL)
timeFrame: Day 1-Day 85.
measure: Apparent volume of distribution during the terminal phase (Vz)
timeFrame: Day 1-Day 85.
measure: Apparent terminal elimination rate constant (λz or kel)
timeFrame: Day 1-Day 85.
measure: Levels of ADA
timeFrame: Day 1-Day 85
Other outcomes:
Locations:
city: Herston
country: Australia
facility: Q-Pharm Pty Ltd, Clive Berghofer Cancer Research Centre
state: Queensland
Study officials:
affiliation: Nucleus Network
name: Richard Friend
role: PRINCIPAL_INVESTIGATOR
References: