Clinical trial NCT05895565: A Multiple Ascending Doses (MAD) Study of PMG1015 in Idiopathic Pulmonary Fibrosis Subjects
Official title: A Phase 1b, Multicenter, Randomized, Double-blind, Placebo-controlled Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of PMG1015 in Idiopathic Pulmonary Fibrosis (IPF) Subjects
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: IPF
Lead sponsor: Pulmongene Ltd.
Sponsor class: INDUSTRY
First posted: 2023-06-08
Enrollment: 28
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase 1b randomized, double-blind, placebo-controlled, multiple ascending doses (MAD) study of PMG1015 in idiopathic pulmonary fibrosis (IPF) subjects. This study aims to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of PMG1015 after MAD.


Eligibility criteria: Key Inclusion Criteria:

1. Diagnosis of IPF as defined by current American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) Clinical Practice Guidelines for IPF (2022) (Pathological examination refers to transbronchial lung cryobiopsy or surgical/pleuroscopic lung biopsy);
2. Forced vital capacity percent predicted (FVCpp) ≥45% at screening;
3. Diffusing capacity of the lung for carbon monoxide (DLCO; corrected for haemoglobin) from 30% to 90% of the predicted, inclusive at screening;
4. Subjects not receiving any approved IPF treatment (pirfenidone or nintedanib) within 1 month before enrollment for any reasons

Key Exclusion Criteria:

1. Patients with instable condition of IPF as assessed by the investigator at screening, and those with acute exacerbation of IPF during screening or within 3 months prior to randomization;
2. Patients who are likely to be lung transplant recipients within 6 months or expected to survive less than 1 year as assessed by the investigator at screening;
3. Patients accompanying with an interstitial lung disease other than IPF;
4. Patients accompanying with other types of respiratory disorders, which may affect the study results as assessed by the investigator;
5. Patients who received vasodilator therapy for pulmonary arterial hypertension (e.g. Bosentan) within 1 month prior to screening;
6. Patients accompanying with other uncontrolled underlying diseases, for which the patient is not considered suitable for the study as assessed by the investigator;
7. Patients who had active tuberculosis within 12 months prior to screening, or clinical symptoms of bacterial, viral, fungal or microbial infections requiring intervention within 4 weeks prior to randomization;
8. Patients who have known allergic reaction to the investigational product or its active pharmaceutical ingredients (APIs), or history of allergic reaction to human, humanized, chimeric, or murine monoclonal antibodies or any substances contained in the excipients;
9. Pregnant or lactating women; female subjects who plan to become pregnant during the study, or patients who are not willing to take contraceptive measures as required by the protocol during the study;
10. Other conditions that preclude the patient from participating in the study as assessed by the investigator.

Primary outcomes:
measure: The incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Approximately 170 days.
measure: The severity of treatment-emergent adverse events (TEAEs)
timeFrame: Approximately 170 days.
measure: The incidence of serious adverse events (SAEs)
timeFrame: Approximately 170 days.
measure: The severity of serious adverse events (SAEs)
timeFrame: Approximately 170 days.
measure: Assessment of pulmonary function test results-forced vital capacity (FVC)
timeFrame: Approximately 170 days.
measure: Assessment of pulmonary function test results-forced vital capacity percent predicted (FVCpp)
timeFrame: Approximately 170 days.
measure: Assessment of pulmonary function test results-forced expiratory volume in 1 second (FEV1)
timeFrame: Approximately 170 days.
measure: Assessment of pulmonary function test results-diffusing capacity of the lungs for carbon monoxide (DLCO)
timeFrame: Approximately 170 days.
measure: Assessment of pulmonary function test results-diffusing capacity of the lungs for carbon monoxide percent predicted (DLCOpp)
timeFrame: Approximately 170 days.
Secondary outcomes:
measure: Evaluate the area under the serum drug concentration-time curve from time zero to the last quantifiable time point (AUC0-t) of PMG1015.
timeFrame: Approximately 170 days.
measure: Evaluate the area under the serum drug concentration-time curve from time zero to infinity (AUC0-∞) of PMG1015.
timeFrame: Approximately 170 days.
measure: Evaluate the area under the concentration-time curve from time zero to the end of a dosing interval (AUC0-tau) of PMG1015.
timeFrame: Approximately 170 days.
measure: Evaluate the maximum concentration (Cmax) of PMG1015.
timeFrame: Approximately 170 days.
measure: Evaluate the time to reach the maximum concentration (Tmax) of PMG1015.
timeFrame: Approximately 170 days.
measure: Evaluate the half-life (t1/2) of PMG1015.
timeFrame: Approximately 170 days.
measure: Evaluate the clearance rate (CL) of PMG1015.
timeFrame: Approximately 170 days.
measure: Evaluate the distribution volume (Vz) of PMG1015.
timeFrame: Approximately 170 days.
measure: Evaluate the elimination rate constant (λz) of PMG1015.
timeFrame: Approximately 170 days.
measure: Relationship between the dose and exposure.
timeFrame: Approximately 170 days.
measure: Incidence of PMG1015-induced and PMG1015-boosted ADAs.
timeFrame: Approximately 170 days.
Other outcomes:
Locations:
city: Hefei
country: China
facility: Site 07
state: Anhui
city: Beijing
country: China
facility: Site 01
state: Beijing
city: Guangzhou
country: China
facility: Site 06
state: Guangdong
city: Wuhan
country: China
facility: Site 03
state: Hubei
city: Nanjing
country: China
facility: Site 04
state: Jiangsu
city: Shanghai
country: China
facility: Site 02
state: Shanghai
city: Shanghai
country: China
facility: Site 05
state: Shanghai
Study officials:
affiliation: China-Japan Friendship Hospital
name: Wang
role: PRINCIPAL_INVESTIGATOR
affiliation: China-Japan Friendship Hospital
name: Dai
role: PRINCIPAL_INVESTIGATOR
References: