UMIN-CTR Clinical Trial

Basic information
Public title	An exploratory study to determine the genetic polymorphisms or mutations associated with type 1 diabetes and interstitial lung disease induced by immune checkpoint inhibitor; nivolumab
Acronym	An exploratory study to determine the irAE-related genes induced by immune checkpoint inhibitor; nivolumab
Scientific Title	An exploratory study to determine the genetic polymorphisms or mutations associated with type 1 diabetes and interstitial lung disease induced by immune checkpoint inhibitor; nivolumab
Scientific Title:Acronym	An exploratory study to determine the irAE-related genes induced by immune checkpoint inhibitor; nivolumab
Region	Japan

Condition
Condition	type 1 diabetes interstitial lung disease
Classification by specialty	Pneumology Endocrinology and Metabolism
Classification by malignancy	Others
Genomic information	YES

Objectives
Narrative objectives1	The aim of study to identify the causal variants or mutations associated with immune-related adverse events (type 1 diabetes and interstitial lung disease) of anti-PD-1 antibody; nivolumab by whole genome analysis in multi-center cohort study.
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Not applicable

Assessment
Primary outcomes	Allele frequency of causal variants or mutations associated with immune-related adverse events of nivolumab
Key secondary outcomes

Base
Study type	Observational

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	The cohort includes the patients treated with nivolumab who develops type 1 diabetes (n=15) and interstitial lung disease(n=50) as case group and the patients without immune-related adverse events (n=65) as control group. Whole genome data in healthy subjects were utilized from Tohoku Medical Megabank or NBDC as a collaboration.
Key exclusion criteria	The patient whom the researcher consider to be inappropriate for the study.
Target sample size	130

Research contact person
Name of lead principal investigator	1st name Atsushi Middle name Last name Kawakami
Organization	Nagasaki University Hospital
Division name	Department of Immunology and Rheumatology
Zip code	852-8501
Address	1-7-1 Sakamoto Nagasaki, Japan
TEL	095-819-7260
Email	atsushik@nagasaki-u.ac.jp

Public contact
Name of contact person	1st name Norio Middle name Last name Abiru
Organization	Nagasaki University Hospital
Division name	Department of Endocrinology and Metabolism
Zip code	852-8501
Address	1-7-1 Sakamoto Nagasaki, Japan
TEL	095-819-7260
Homepage URL
Email	abirun@nagasaki-u.ac.jp

Sponsor
Institute	Nagasaki University Hospital
Institute
Department

Funding Source
Organization	Investigators Supported Research Grants from ONO PHARMACEUTICAL CO. LTD. and Bristol-Myers Squibb
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor	National Cancer Center Hospital Tochigi cancer center Kyusyu University Kurume University University of Occupational and Environmental Health Fukuoka University Oita University Kumamoto University Kagoshima University University of the Ryukyu University of Miyazaki Saga University Tokai University School of Medicine Japanese Red Cross Nagasaki Genbaku Hospital National Hospital Nagasaki Medical Center JCHO Isahaya General Hospital Nagasaki Prefecture Shimabara Hospital Sasebo City General Hospital Kitakyusyu Munincipal Medical Center NHO Fukuoka Higashi Medical Center NHO Ureshino Medical Center JCHO Kyusyu Hospital Kagoshima City Hospital Saitama Medical University International Medicak Center Hokkaido University Kanazawa University Kyoto Prefectural University of Medicine Okayama University Chiba University
Name of secondary funder(s)

IRB Contact (For public release)
Organization	The Clinical Research Review Board in Nagasaki University
Address	1-7-1 Sakamoto Nagasaki-shi, Nagasaki-ken
Tel	095-819-7905
Email	gaibushikin@ml.nagasaki-u.ac.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	長崎大学病院

Other administrative information
Date of disclosure of the study information	2017 Year 12 Month 21 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Enrolling by invitation
Date of protocol fixation	2017 Year 12 Month 18 Day
Date of IRB	2017 Year 12 Month 19 Day
Anticipated trial start date	2018 Year 02 Month 01 Day
Last follow-up date	2020 Year 12 Month 14 Day
Date of closure to data entry	2021 Year 01 Month 31 Day
Date trial data considered complete	2021 Year 03 Month 31 Day
Date analysis concluded	2022 Year 03 Month 31 Day

Other

Other related information

Collecting information 1. for case and control sex, age, height, weight, primary disease to nivolumab, the date of start of nivolumab, number of nivolumab injection 2-1. for type 1 diabetes case Hyperglycemic symptom, the date of unconsciousness or diagnosis of type 1 diabetes Exam on diagnosis; Blood and biochemistry; WBC, RBC, Hb, Hct, Pelt, Plasma glucose, HbA1c, Urine or blood Ketone body, blood gas, pancreatic enzyme(Amylase, elastase1, lipase), anti-GAD antibody, serum and urine C-peptide, 2-2. for interstitial lung disease case initial symptom (short of breath, dyspnea, cough), the date of audible of rale or diagnosis of interstitial lung disease Treatment for interstitial lung disease Exam on diagnosis; Image;chest X-ray, HRCT Blood and biochemistry; WBC, RBC, Hb, Hct, Plt, CRP, AST, ALT, g-GTP, KL-6,SP-A, SP-D, blood gas Exam for differential diagnosis; b-D-glucan, cytomegalo virus antigen, sputum examination (Bacterial smear or culture) 3.genome data; Genomic DNA from obtained 10mL of blood sample is collected. The genome DNA is analyzed by whole genome analysis to serach for the causal variants or mutations associated with immune-related adverse events (type 1 diabetes and interstitial lung disease) of anti-PD-1 antibody; nivolumab. 4. Serum sample data Serum sample is collected and the level of anti-GAD, serum-C-peptide, KL-6 and SP-D are measured to support the diagnosis of disease or non-disease.

Management information
Registered date	2017 Year 12 Month 20 Day
Last modified on	2021 Year 07 Month 02 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034813