Symptoms and General Pathology

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Fibrosis

Pulmonary Fibrosis

Lung Diseases

Lung Diseases, Interstitial

Respiratory Tract Diseases

single dose escalation for experimental drug

matching placebo administration for control

Single dose intravenously infused on day 1

9MW3811 injection

Single dose of matching placebo intravenously infused on day 1

Placebo

Christopher Argent

PUJA MOTWANI

This is a first-in-human, single ascending dose study of 9MW3811, the primary objective of which is to evaluate the safety and tolerability of 9MW3811 in healthy adult participants.

The single ascending dose study will comprise 4 dose cohorts of 8 healthy participants each. In each cohort, participants will be randomized to receive 9MW3811 or placebo by 6:2.

A Study to Evaluate the Safety, Tolerability and Pharmacokinetic Properties of 9MW3811 in Healthy Subjects

A Phase 1, First-in-human, Randomized, Double-blind，Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetic, Pharmacodynamics and Immunogenicity of 9MW3811 in Healthy Adult Participants

To explore the pharmacodynamics (PD) of 9MW3811.

An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

The physical examinations will include examination of the following: head, eyes, ears, nose and throat, neck (including thyroid \& nodes), cardiovascular system, dermatological system, musculoskeletal system, respiratory system, gastrointestinal system, neurological system and renal system.

The examination indicators include heart rate, PR, QRS, uncorrected QT, and QTcF \[corrected by Fridericia formula, QTcF = QT/(RR\^0.33), RR is the standardized heart rate value, which is obtained by dividing 60 by the heart rate\].

Vital signs measurements will include pulse rate, respiration rate, blood pressure (systolic and diastolic blood pressure) and body temperature.

Clinical laboratory tests include hematology, urinalysis, blood chemistry, coagulation function.

To determine the pharmacokinetic (PK) of 9MW3811 following single ascending intravenous doses in healthy adult participants.

To determine the PK of 9MW3811 following single ascending intravenous doses in healthy adult participants.

To determine the immunogenicity of 9MW3811.

Mabwell (Shanghai) Bioscience Co., Ltd.

Neoplasms

Digestive System Diseases

Infections

Wounds and Injuries

Rare Diseases

Esophageal Neoplasms

Carcinoma

Adenocarcinoma

Respiratory Insufficiency

Carcinoma, Squamous Cell

Pneumonia

Radiation Pneumonitis

Radiation Fibrosis Syndrome

Syndrome

Communicable Diseases

Respiratory Tract Infections

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Respiration Disorders

Lung Injury

Radiation Injuries

Esophageal Cancer

FEV1, FVC and DLCO will be assessed at baseline and one month post induction therapy. Radiation induced lung injury (RILI EORTC grade≥2), CCI, Clavien-Dindo, and pulmonary complications will be monitored. Changes in pulmonary function will be compared with cardiorespiratory symptoms and HR-QL among disease-free survivors.

Esophagectomy

Although recent global trends indicate reduced postoperative mortality after esophagectomy, major morbidity, in particular pulmonary, remains high, with considerable health and economic costs. In a recent modern international collaborative series of 2704 patients from high-volume centers, with an approximate equal mix of open and minimally invasive approaches, respiratory complications were evident in 28% of patients, pneumonia in 15%, and respiratory failure in 7%.1 In other series, respiratory failure is reported in up to 15% of patients and is the most common cause of mortality. Prediction of risk and prevention of respiratory morbidity is therefore of considerable importance, and in this context baseline assessment of respiratory physiology compliments clinical assessment, history and enhanced recovery pathways representing key elements of current patient management.

In this study, which will include all prospective patients with locally advanced esophageal cancer treated at a National Center, pulmonary function will be systematically measured before and after neoadjuvant therapy. The investigators seek to evaluate the incidence of radiation induced lung injury (RILI), as well as subclinical changes in pulmonary physiology that may be linked to postoperative complications, and quality-of-life in survivorship, and to compare cohorts who received radiation therapy or chemotherapy alone, preoperatively.

Neoadjuvant Therapy for Esophageal Cancer and Cardiopulmonary Physiology

Neoadjuvant Therapy for Locally Advanced Esophageal Cancer: Impact on Cardiopulmonary Physiology, Short- and Long-term Morbidity

Changes in FEV1 (forced expiratory volume in one second, litres), both as a raw value, and as percentage of predicted values normalized for ethnicity, sex, age and height according to Global Lung Function Initiative algorithms will be determined.

Changes in FVC (forced vital capacity, litres), both as a raw value, and as percentage of predicted values normalized for ethnicity, sex, age and height according to Global Lung Function Initiative algorithms will be determined.

Changes in DLCO (pulmonary diffusion capacity for carbon monoxide, mmol·min.-1.kPa. -1), both as a raw value, and as percentage of predicted values normalized for ethnicity, sex, age and height according to Global Lung Function Initiative algorithms will be determined.

Incidence of postoperative pulmonary morbidity, defined according to ECCG guidelines, will be compared after neoadjuvant chemotherapy versus chemoradiation.

"Global health" HR-QL scores at one year postoperatively among disease-free patients will be compared between neoadjuvant chemotherapy and chemoradiation cohorts

Disease-free survival will be compared between neoadjuvant chemotherapy and chemoradiation groups using Kaplan-Meier methods, as well as multivariable Cox proportional hazards regression models adjusting for known prognostic factors.

St. James's Hospital, Ireland

Surgical Research Fellow

Immune System Diseases

Blood and Lymph Conditions

Asthma

Sarcoidosis

Lymphangioleiomyomatosis

Hypersensitivity

Lymphoproliferative Disorders

Lymphatic Diseases

Hypersensitivity, Delayed

Lymphangiomyoma

Neoplasms by Histologic Type

Perivascular Epithelioid Cell Neoplasms

Neoplasms, Connective and Soft Tissue

Immunoproliferative Disorders

Joel Moss, M.D.

This study will examine bacteria and toxins in the mouth, lung and digestive system that may be the cause of various diseases or symptoms. H. pylori is a bacterium that produces various toxins that may contribute to lung problems. This study will examine specimens collected from the mouth, teeth, lung, digestive tract and blood to measure H. pylori and its toxins and their effects on cells.

People 18 years of age and older with or without gastrointestinal disease may be eligible for this study. These include people without a history of lung disease as well as patients with any of the following: lymphangioleiomyomatosis, asthma, sarcoidosis, other chronic or genetic lung disease (e.g., chronic obstructive pulmonary disease, cystic fibrosis or eosinophilic granuloma).

Participants may undergo the following tests:

* Blood and urine tests, chest x-ray.
* Measurement of arterial blood gases: A small needle is placed in an artery in the forearm to collect arterial blood.
* Lung function tests: Subjects breathe deeply and occasionally hold their breath. They may also receive a medication that expands the airways.
* Fiberoptic bronchoscopy with lavage and bronchial brushing: The subject's mouth and throat are numbed with lidocaine; a sedative may be given for comfort. A thin flexible tube called a bronchoscope is advanced through the nose or mouth into the lung airways to examine the airways. Saline (salt water) is then injected through the bronchoscope into the air passage and then removed by gentle suction. Next, a small brush is passed through the bronchoscope and an area of the airway is brushed to collect some cells for examination.
* Mouth rinsing or teeth brushing to collect cells.
* Endoscopy: A small needle and catheter (thin plastic tube) are placed into an arm vein to administer fluids and medications through the vein. A sedative may be given. The throat is numbed with lidocaine and a thin flexible tube called an endoscope is inserted through the mouth and down the esophagus into the stomach and upper part of the small intestine to examine those areas.

Vacuolating cytotoxin A (VacA toxin), an 88-kDa multifunctional protein, and other toxins are produced by Helicobacter pylori. We hypothesize that H. pylori, VacA toxin, and other toxins within the gastrointestinal tract and/or oropharynx are also found in the lung and may contribute to decline in lung function. Analyses of gastrointestinal, oropharyngeal, lung and blood specimens will improve the understanding of H. pylori, VacA toxin, and other toxins as well as their potential role in pathophysiology of disease. The objectives of this exploratory protocol are to procure gastrointestinal, oropharyngeal, lung and/or blood specimens from healthy research volunteers and subjects with lung disease (e.g., lymphangioleiomyomatosis, asthma, sarcoidosis, pulmonary fibrosis) and to analyze these specimens for H. pylori, VacA toxin, and other toxins. We hypothesize that the toxins may have a role in the pathogenesis of lung disease and in the subclinical decline in lung function seen with aging.

Role of Helicobacter Pylori and Its Toxins in Lung and Digestive System Diseases

Role of Helicobacter Pylori and Its Toxins in Pulmonary and Oropharyngeal Disease

Procure and analyze gastrointestinal, oropharyngeal, lung and/or blood specimens from healthy research volunteers and subjects with lung disease (e. g., lymphangioleiomyomatosis, asthma, sarcoidosis, pulmonary fibrosis). Comparison of specimens from subjects may further the understanding of H. pylori, VacA cytotoxin, and/or other toxins in oropharyngeal, pulmonary, and gastrointestinal conditions.

National Heart, Lung, and Blood Institute (NHLBI)

Lung Neoplasms

Idiopathic Pulmonary Fibrosis

Respiratory Tract Neoplasms

Thoracic Neoplasms

Healthy volunteers will receive \[68Ga\]CBP8 and undergo PET imaging.

Lung cancer patients will receive \[68Ga\]CBP8 and undergo PET imaging.

Idiopathic pulmonary fibrosis patients or patients with other types of interstitial lung disease with a fibrotic component will receive \[68Ga\]CBP8 and undergo PET imaging.

Up to 15 mCi of \[68Ga\]CBP8 will be administered to each subject.

[68Ga]CBP8

All subjects will undergo PET imaging after administration of \[68Ga\]CBP8.

PET Imaging

Sydney B Montesi, MD

Layla Rahimi

Sydney Montesi, MD

The goal of this study is to investigate the safety of \[68Ga\]CBP8 and its efficacy to detect collagen deposition in pulmonary fibrosis.

The investigators have developed \[68Ga\]CBP8, a gallium-68 labeled collagen binding PET imaging probe, which selectively binds collagen type I. Collagen deposition is a pivotal event in several human conditions including pulmonary fibrosis. The investigator's studies in mice showed that \[68Ga\]CBP8 binds collagen with high affinity and has excellent pharmacological and pharmacokinetic profiles with high target uptake and low retention in background tissues and organs. \[68Ga\]CBP8 was shown in a mouse model to be effective for detecting lung fibrosis. \[68Ga\]CBP8 showed high specificity for pulmonary fibrosis and high target:background ratios in diseased animals. In addition, \[68Ga\]CBP8 could be used to monitor response to treatment. Ex vivo analysis of lung tissue from patients with IPF supported the animal findings.

The investigators thus aim to perform the first in human studies of \[68Ga\]CBP8:

1. To evaluate the safety of \[68Ga\]CBP8 and its whole body distribution, metabolism, pharmacokinetics, and radiation burden in healthy volunteers.
2. To establish the accuracy of \[68Ga\]CBP8-PET to detect radiation-induced fibrosis in lung cancer patients and correlate collagen-targeted \[68Ga\]CBP8-PET imaging with HRCT and histology in lung cancer patients.
3. To determine whether collagen deposition as assessed by \[68Ga\]CBP8-PET molecular imaging can predict disease progression in IPF patients and patients with other types of ILD with a fibrotic component.

Healthy control subjects will be enrolled first and then subjects with lung cancer and idiopathic pulmonary fibrosis or other types of interstitial lung disease with a fibrotic component meeting inclusion criteria.

Preliminary Evaluation of [68Ga]CBP8 in Healthy Individuals, Lung Cancer, and Idiopathic Pulmonary Fibrosis Patients

Preliminary Evaluation of [68Ga]CBP8 in Healthy Individuals, Lung Cancer Patients Undergoing Radiation Therapy Prior to the Resection of Locally Advanced Tumors, and Idiopathic Pulmonary Fibrosis Patients

Probe lung uptake will be measured in lung cancer patients prior to surgical resection and compared to histologic measures of fibrosis.

Probe lung uptake will be measured in pulmonary fibrosis subjects and compared to lung uptake in healthy volunteers. We expect greater uptake in the lungs of IPF patients and patients with other types of ILD with a fibrotic component.

Probe lung uptake in pulmonary fibrosis patients will be correlated with change in forced vital capacity over the prior 12 months and prospectively over the following 12-36 months.

Massachusetts General Hospital

Professor of Radiology

Diseases and Abnormalities at or Before Birth

Nervous System Diseases

Skin and Connective Tissue Diseases

Sclerosis

Cystic Fibrosis

Alpha 1-Antitrypsin Deficiency

Tuberous Sclerosis

Sarcoidosis, Pulmonary

Pancreatic Diseases

Genetic Diseases, Inborn

Infant, Newborn, Diseases

Hamartoma

Neoplasms, Multiple Primary

Neoplastic Syndromes, Hereditary

Congenital Abnormalities

Malformations of Cortical Development

Nervous System Malformations

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Alpha-1 Antitrypsin Deficiency

Tuberous Sclerosis Complex

Vasodilator Agents

Respiratory System Agents

All Drugs and Chemicals

Nitric Oxide

Alpha 1-Antitrypsin

Protein C Inhibitor

Subjects with pulmonary disease or possible pulmonary disease and Relatives

Tatyana Worthy, R.N.

Tatyana Worthy, B.S.

This study is designed to evaluate the genetics involved in the development of lung disease by surveying genes involved in the process of breathing and examining the genes in lung cells of patients with lung disease.

The study will focus on defining the distribution of abnormal genes responsible for processes directly involved in different diseases affecting the lungs of patients and healthy volunteers.

Optional CT Sub-study

The standard CT scan will be compared to the low dose radiation CT scan for the 150 subjects enrolled in the sub-study to assess the variation between the two techniques. Specifically, the quantitative computer aided detection of lung CT abnormalities from LAM can be compared to assess whether low radiation dose CT exams is an alternative to conventional CT to monitor disease

status.

This optional sub-study will be offered to up to 100 adult subjects with lung disease and up to 50 children age 9 and older with CF. Children will not be enrolled in the optional CT sub-study unless they have had a standard CT scan for medical purposes to use in comparison. One additional low dose radiation CT scan of the chest may be done as part of this sub-study when these subjects have their next annual CT scan.

This study is designed to evaluate genetic mechanisms of lung disease by surveying polymorphic genes involved in respiratory function and examining gene expression in the lung cells of individuals with pulmonary disease (e.g., alpha 1-antitrypsin deficiency, asthma, chronic obstructive pulmonary disease, cystic fibrosis, sarcoidosis, history of infection, and genetic mutations consistent with lung pathology). Emphasis will be on defining the distribution of allelic variants of nitric oxide synthase, alpha 1-antitrypsin, and the cystic fibrosis transmembrane conductance regulator genes in patients and in age- and sex-matched healthy individuals in a control population.

Role of Genetic Factors in the Development of Lung Disease

Role of Genetic Factors in the Pathogenesis of Lung Disease

.This is a new requirement and the sharing of IPD is not discussed in the protocol.

distribution of genetic variants of nitric oxide synthases and other candidate genes involved in pulmonary function

The secondary scan can also be used to obtain a detailed assessment of AML-like tumors and lymphangioleiomyomas in the abdomen or pelvis region when they are detected in the standard chest-abdomen-pelvis CT scan. The enhanced resolution is expected to help classify the tumors without the need for invasive biopsy, for example, by detecting traces of fatty tissue in the tumor to confirm the identity of AML.

Suburban Hospital

Heart and Blood Diseases

Ear, Nose, and Throat Diseases

Occupational Diseases

Behaviors and Mental Disorders

Lung Diseases, Obstructive

Pulmonary Disease, Chronic Obstructive

Hypertension

Apnea

Sleep Apnea Syndromes

Sleep Apnea, Obstructive

Pulmonary Embolism

Embolism

Pulmonary Emphysema

Emphysema

Hypertension, Pulmonary

Mesothelioma

Mesothelioma, Malignant

Virus Diseases

Bronchiectasis

Rhinitis, Allergic, Seasonal

Asbestosis

Vascular Diseases

Parasomnias

Sleep Disorders, Intrinsic

Dyssomnias

Sleep Wake Disorders

Chronic Disease

Disease Attributes

Thrombosis

Embolism and Thrombosis

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms, Mesothelial

Bronchial Diseases

Pneumoconiosis

Chronic Graft Versus Host Disease

Malignant Mesothelioma

Coal Worker's Pneumoconiosis

Central Nervous System Depressants

Xenon

Participants will inhale investigational gases (HP 3He, HP 129Xe, PFP and SF6) according to the procedure for that intervention. All participants can potentially inhale all the gases. Magnetic resonance imaging will be performed during breath-holds or continuous breathing (gas-dependent) with the appropriate investigational human lung coil (3He Human Lung Coil, 129Xe Small and Large Human Lung Coil, or PFP and SF6 Human Lung Coil), using the 3T Research MRI at the Thunder Bay Regional Health Sciences Centre.

3He will be hyperpolarized using a custom-built polarizer to enhance its MRI signal. Hyperpolarization does not change the chemical or physical properties of helium gas.

HP 3He

129Xe will be hyperpolarized using a Xemed polarizer to enhance its MRI signal. Hyperpolarization does not change the chemical or physical properties of xenon gas.

HP 129Xe

Perfluoropropane (PFP) will be premixed and delivered to the participants with no further processing.

Sulfur hexafluoride (SF6) will be premixed and delivered to the participant with no further processing.

The investigational 129Xe small and large quadrature lung coils are sensitive to 129Xe resonant frequencies and therefore will be paired with the investigational drug 129Xe. The size of the coil used will depend on the participants' body size.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Evaluate the Safety, Tolerability and Pharmacokinetic Properties of 9MW3811 in Healthy Subjects	NCT05740475	Pulmonary Fibro... Tumor	9MW3811 injecti... Placebo	18 Years - 55 Years	Mabwell (Shanghai) Bioscience Co., Ltd.
Neoadjuvant Therapy for Esophageal Cancer and Cardiopulmonary Physiology	NCT03462524	Esophageal Canc... Radiation Pneum... Pulmonary Fibro... Respiratory Fai... Pneumonia Surgery Chemotherapy Ef... Radiation Fibro... Radiation Toxic... Adenocarcinoma Squamous Cell C...	Esophagectomy	18 Years -	St. James's Hospital, Ireland
Role of Helicobacter Pylori and Its Toxins in Lung and Digestive System Diseases	NCT00366509	Pulmonary Disea... Oropharyngeal D... Lymphangioleiom... Pulmonary Fibro... Asthma Sarcoidosis		18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
Preliminary Evaluation of [68Ga]CBP8 in Healthy Individuals, Lung Cancer, and Idiopathic Pulmonary Fibrosis Patients	NCT03535545	Pulmonary Fibro... Lung Cancer	[68Ga]CBP8 PET Imaging	18 Years - 80 Years	Massachusetts General Hospital
A Study to Evaluate the Safety, Tolerability and Pharmacokinetic Properties of 9MW3811 in Healthy Subjects	NCT05740475	Pulmonary Fibro... Tumor	9MW3811 injecti... Placebo	18 Years - 55 Years	Mabwell (Shanghai) Bioscience Co., Ltd.
Role of Genetic Factors in the Development of Lung Disease	NCT00001532	Cystic Fibrosis Pulmonary Fibro... Tuberous Sclero... Asthma Pulmonary Sarco...		2 Years - 90 Years	National Institutes of Health Clinical Center (CC)
Developing Optimal Parameters for Hyperpolarized Noble Gas and Inert Fluorinated Gas MRI of Lung Disorders	NCT02748798	Lung Transplant Lung Resection Lung Cancer Asthma Cystic Fibrosis Chronic Obstruc... Emphysema Mesothelioma Asbestosis Pulmonary Embol... Interstitial Lu... Pulmonary Fibro... Bronchiectasis Seasonal Allerg... Cold Virus Lung Infection Pulmonary Hyper... Pulmonary Dyspl... Obstructive Sle...	HP 3He HP 129Xe PFP SF6 129Xe Small and... 3He Human Lung ... PFP and SF6 Hum...	18 Years -	Thunder Bay Regional Health Research Institute

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