Safety and Preliminary Clinical Activity of Itolizumab in ARDS

A Phase 1 Study to Evaluate the Safety, Tolerability and Preliminary Clinical Activity of Itolizumab in Subjects With Acute Respiratory Distress Syndrome Caused by Infectious Pneumonia

To evaluate the safety, tolerability, PK, PD, and clinical activity of Itolizumab in subjects with acute respiratory distress syndrome (ARDS) caused by Infectious Pneumonia.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: Itolizumab

Detailed Description

The study will enroll approximately 38 subjects in two parts:

Part 1 is an open label 3+3 single dose escalation phase. 9-24 patients with ARDS caused by infectious pneumonia across 3 dose cohorts.

Part 2 is a randomized phase and will enroll approximately 14 additional participants, randomized in a 1:1 ratio to one of the 2 doses based on efficacy data obtained from Part 1.

All participants in this study will receive Itolizumab intravenously for once, investigator discretion to continue with the same dose every 3 days up to 7 days.

• Study Type: Interventional
• Enrollment (Estimated): 38
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: DANDAN Gao; Phone Number: 010-51571020; Email: gaodandan@biotechplc.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female subject aged 18-75 years old (inclusive)
2. Clinical diagnosis with infectious pneumonia as determined by the investigator
3. Subject who havd received anti-infective treatment according to clinical practice.
4. Diagnosis with ARDS according to the following criteria: (i) Bilateral opacities-not fully explained by effusions, lobar/lung collapse, or nodules; (ii) respiratory failure not fully explained by cardiac failure or fluid overload; (iii) Oxygenation (PaO2/FiO2) ≤300.
5. ARDS diagnosed within 48 hours before administration, and fullfil the criteria of ARDS before administration
6. Fullfill at least 2 of the following 4 criteria: ① elevated hs-CRP (>6 ULN); ② elevated IL-6 (>3 ULN); ③ high serum ferritin (>500µg/L at any one time or more than 2-fold increase within 48 hours of onset); ④ high D-dimer (>3 ULN).
7. Negative result of serum HCG within 72 hours before enrollment for female with potential fertility
8. Participant or his/her legal representive (when the participant is not capable of giving consent) is able to understand and comply with the planned procedure as required by the protocol, and sign a written informed consent form (ICF)

Exclusion Criteria:

1. ARDS caused by non-infectious pneumonia (e.g., burns, drowning, poisoning, etc.)
2. Subject who has cardiogenic pulmonary edema, and it is the main cause of respiratory failure
3. Subject who is at high risk of death within 24 hours regardless of the treatment measures given as determined by the investigator
4. Subject who is receiving extracorporeal membrane pulmonary oxygenation (ECMO) therapy at the time of screening.
5. Subject who had received mechanical ventilation for more than 72 hours prior to administration.
6. Subject with active tumors (other than carcinoma in situ or basal cell carcinoma) that requiring treatment.

7. Any of the following chronic organ damage or immunosuppression:

   1. Cardiac: cardiac arrest within 7 days prior to screening; New York Heart Association cardiac function class IV at screening;
   2. Pulmonary: oxygen therapy or ventilator-dependent therapy for more than 1 month cumulatively within 6 months prior to screening; pulmonary embolism within 4 weeks prior to screening; pulmonary hypertension, end-stage lung disease, or interstitial lung disease requiring glucocorticoid therapy at screening;
   3. Renal: serum creatinine > 1.5 ULN or creatinine clearance < 30 mL/min at screening (Cockcroft-Gault formula, see study protocol annex 5 for details) or on long-term dialysis treatment;
   4. Liver: liver function classification of Child-Pugh grade C at screening;
   5. Immunosuppression status: with lymphoma, leukemia or acquired immunodeficiency; having received antitumor chemotherapy in the last 3 months, or being treated with immunosuppression for organ transplantation or immune disorders; having had allogeneic bone marrow transplantation or allogeneic hematopoietic stem cell transplantation.
8. Subject who had vaccination within 28 days prior to administration, or plan to get the vaccine during the study period

9. Any of the following abnormalities at screening

   1. Hepatitis B-related tests: ① positive for hepatitis B surface antigen (HBsAg); ② positive for hepatitis B core antibody (HBcAb); ③ positive for hepatitis B surface antibody (HBsAb) and no history of hepatitis B vaccination; ④ positive for hepatitis B e antigen or hepatitis B e antibody;
   2. Positive hepatitis C virus antibody (HCV-Ab);
   3. Positive acquired immunodeficiency syndrome antibody (HIV-Ab).
10. Subject who has a medical history of tuberculosis or those who deny a history of tuberculosis but has a positive gamma-interferon release test at screening.
11. Absolute lymphocyte count < 0.2×109/L at screening
12. Suspected allergic to the investigational drug or any of its excipients
13. Currently pregnant, breastfeeding,or planning to become pregnant or not using reliable method to avoid pregnancy during study and within 3 months after the last study treatment
14. Subject who had participated in other clinical studies (other than those not receiving interventions, such as observational study or questionnaires survey) within 3 months prior to screening, or who are participating in other experimental treatments.
15. As determined by the investigator, any medical, psychiatric, or other condition or circumstance that is likely to negatively affect the reliability of the study data.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Itolizumab Dose Level 1; Itolizumab of 50 mg administered by intravenous infusion for once, investigator discretion to continue with the same dose every 3 days up to 7 days.	Drug: Itolizumab; Patients to be treated with Itolizumab.; Other Names: T1h
Experimental: Itolizumab Dose Level 2; Itolizumab of 100 mg administered by intravenous infusion for once, investigator discretion to continue with the same dose every 3 days up to 7 days.	Drug: Itolizumab; Patients to be treated with Itolizumab.; Other Names: T1h
Experimental: Itolizumab Dose Level 3; Itolizumab of 150 mg administered by intravenous infusion for once, investigator discretion to continue with the same dose every 3 days up to 7 days.	Drug: Itolizumab; Patients to be treated with Itolizumab.; Other Names: T1h

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment Emergent Adverse Events	Number of subjects with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) V5.0	Study Day 58

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum serum concentration of Itolizumab, Cmax	Maximum serum concentration of Itolizumab	Study Day 30
Minimum serum concentration of Itolizumab, Cmin	Minimum serum concentration of Itolizumab	Study Day 30
Time to maximum serum concentration of Itolizumab, Tmax	Time to maximum serum concentration of Itolizumab	Study Day 30
Total Itolizumab exposure across time, AUC0-t	Total Itolizumab exposure across time	Study Day 30
Half life of Itolizumab, t1/2	Half life of Itolizumab	Study Day 30
Inflammatory Markers,IL-6	IL-6	Study Day 30
Inflammatory Markers,TNF-α	TNF-α	Study Day 30
Inflammatory Markers, hs-CRP	hs-CRP	Study Day 30
Inflammatory Markers,Serum ferritin	Serum ferritin	Study Day 30
Inflammatory Markers,D-dimer	D-dimer	Study Day 30
CD6 receptor expression levels	Mean change of CD6 receptor expression levels in relative to baseline	Study Day 30
T cell subsets	Mean change of different T cell subsets in relative to baseline	Study Day 30
The proportion of patients with stable or improved Lung Function	Defined as patients with stable or improved PaO2 without increasing FiO2 in relative to baseline	Study Day 30
Mean change from baseline in Murray Score	Mean change of Murray Score in relative to baseline，The higher score means the worse outcome	Study Day 30
Mean change from baseline in SOFA score	Mean change of SOFA（Sequential Organ Failure Assessment） score in relative to baseline，The higher score means the worse outcome	Study Day 30
Mechanical ventilation-free days	Duration of non-Mechanical ventilation	Study Day 30
Oxygen therapy-free days	Duration of non-Oxygen therapy	Study Day 30
Duration of ICU stay	ICU stay days	Study Day 30
Mortality rate	Defined as the proportion of patients who met fatal outcome event by Day 15 and 30	Study Day 15, 30
Clinical status assessed using a 7-category ordinal scale	Clinical status assessed using a 7-category ordinal scale	Study Day 30
Incidence of ADA	Defined as the precentage of subjects presenting anti-drug antibody	Study Day 30

Collaborators and Investigators

• Sponsor: Biotech Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Bin Du, Peking Union Medical College Hospital; Principal Investigator: Huadong Zhu, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): December 31, 2023
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: July 20, 2023
• First Submitted That Met QC Criteria: August 3, 2023
• First Posted (Actual): August 7, 2023

Study Record Updates

• Last Update Posted (Actual): August 7, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: BPL-ITO-ARDS-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No