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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04674683




Registration number
NCT04674683
Ethics application status
Date submitted
7/12/2020
Date registered
19/12/2020
Date last updated
24/06/2024

Titles & IDs
Public title
Study Comparing Investigational Drug HBI-8000 + Nivolumab vs. Placebo + Nivolumab in Patients With Advanced Melanoma
Scientific title
A Multicenter, Randomized, Double-Blind Phase 3 Study of HBI-8000 Combined With Nivolumab Versus Placebo With Nivolumab in Patients With Unresectable or Metastatic Melanoma Not Previously Treated With PD-1 or PD-L1 Inhibitors
Secondary ID [1] 0 0
HBI-8000-303
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Unresectable or Metastatic Melanoma 0 0
Progressive Brain Metastasis 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - HBI-8000 in combination with nivolumab
Treatment: Drugs - Placebo in combination with nivolumab

Experimental: Test Arm - HBI-8000 30 mg oral BIW + nivolumab IV at specific doses on specific days

Placebo comparator: Control Arm - Placebo oral BIW + nivolumab IV at specific doses on specific days


Treatment: Drugs: HBI-8000 in combination with nivolumab
Patients will take 30 mg of HBI-8000 orally approximately 30 minutes after a full meal, beginning on Day 1 and continue every 3 to 4 days on the BIW schedule. On Day 1 of each cycle nivolumab IV will be administered by intravenous infusion at specific doses on specific days in accordance with OPDIVO® manufacturer regional product information insert and the institution's prescribing practice. In adolescent patients with body weight \< 40 kg, nivolumab will be dosed at specific doses on specific days.

Treatment: Drugs: Placebo in combination with nivolumab
Patients will take 30 mg of Placebo orally approximately 30 minutes after a full meal, beginning on Day 1 and continue every 3 to 4 days on the BIW schedule. On Day 1 of each cycle nivolumab IV at specific doses will be administered by intravenous infusion in accordance with OPDIVO® manufacturer regional product information insert and the institution's prescribing practice.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Primary Outcome
Timepoint [1] 0 0
From date of randomization to the earliest date of documented progressive disease (PD), assessed up to 48 months
Secondary outcome [1] 0 0
Objective Response Rate
Timepoint [1] 0 0
From date of randomization until disease progression or unacceptable toxicity, assessed up to 48 months
Secondary outcome [2] 0 0
Overall Survival
Timepoint [2] 0 0
From date of randomization to death due to any cause, assessed up to 48 months
Secondary outcome [3] 0 0
Safety, defined as the incidence rate of AEs
Timepoint [3] 0 0
From date of screening until the end of study, assessed up to 48 months

Eligibility
Key inclusion criteria
1. Histopathologically confirmed diagnosis of non-uveal, Stage III (unresectable), or Stage IV (metastatic) melanoma according to AJCC staging system (8th edition).
2. Known BRAF V600 mutation status or consent to BRAF V600 mutation testing before randomization.
3. Tumor tissue available for PD-L1 testing at central lab or local laboratory; results must be obtained prior to randomization. In the event when archived tumor tissue is not available, new tumor biopsy or historical PD-L1 test results may be used for randomization, however tumor tissue, either taken previously or newly acquired, must be provided for central biomarker confirmation for final data analyses.

PD-L1 expression level is required for randomization. In order to be randomized, a patient must be classified as PD-L1 positive or PD-L1 negative according to the following criteria:
* PD-L1 positive (= 1% tumor cell membrane staining in a minimum of a hundred evaluable tumor cells) vs
* PD-L1 negative (< 1% tumor cell membrane staining in a minimum of a hundred evaluable tumor cells).

Note: If an insufficient amount of tumor tissue is available prior to the start of the screening phase, patients must consent to allow the acquisition of additional tumor tissue for performance of biomarker analyses.
4. Males or females 12 years of age or older.
5. ECOG performance status =1 for age =18 years, Lansky performance status =80% for age 12 to 17 years.
6. At least one measurable lesion defined by RECIST 1.1 criteria, (separate from the lesion to be used for tumor tissue collection) not counting brain metastasis with:

* Longest diameter =10 mm by CT (when slice thickness is =5 mm); or = 2× slice thickness (when slice thickness is >5 mm)
* Pathologically enlarged lymph node: =15 mm in short axis by CT (when slice thickness is =5 mm)
* Clinical: =10 mm (that can be accurately measured with calipers).
7. Have not received anti-PD-1, anti-PD-L1 or other systemic therapy for unresectable or metastatic melanoma, except for the following, provided that the patient has recovered from all treatment-related toxicities:

* BRAF mutation targeting therapy > 4 weeks before administration of Study Treatment.
* Adjuvant or neoadjuvant therapy with PD-1 or PD-L1 inhibitors or anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) is allowed if disease progression/or recurrence had occurred at least 6 months after the last dose of neoadjuvant/adjuvant therapy and prior to receiving the first dose on this study and no clinically significant immune related toxicities leading to treatment discontinuation were observed
* Adjuvant interferon therapy must have been completed > 6 weeks before administration of Study Treatment
8. Any prior radiotherapy or minor surgery must be completed at least 2 weeks and 1 week respectively before Day 1 dosing and recovered from all treatment related toxicities
9. Screening laboratory results within 14 days prior to randomization:

* Hematology: WBC =3000/µL, neutrophils =1500/µL, platelets =100 × 103/µL, hemoglobin =10.0 g/dL independent of transfusion. The use of erythropoietic growth factor to achieve hemoglobin (Hgb) = 10 g/dl is acceptable.
* The CrCL= 30 mL/min using Cockcroft-Gault formula.
* AST and ALT =3 × ULN, alkaline phosphatase =2.5 × ULN unless bone metastases present (patients with documented bone metastases: alkaline phosphatase <5 x ULN), bilirubin = 1.5 × ULN (unless known Gilbert's disease where it must be = 3 × ULN), serum albumin = 3.0 g/dL).
10. Negative serum pregnancy test at baseline for women of childbearing potential.
11. Females of childbearing potential (non-surgically sterile or premenopausal female capable of becoming pregnant) and all males (due to potential risk of drug exposure through the ejaculate) must agree to use adequate birth control measures from study start, during the study and for 5 months after the last dose of Study Drug. Acceptable methods of birth control in this trial include two highly effective methods of birth control (as determined by the Investigator; one of the methods must be a barrier technique) or abstinence.
12. Have the ability to understand and the willingness to sign a written informed consent document, comply with study scheduled treatment, visits and assessments.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of = Grade 3 hypersensitivity reactions to monoclonal antibodies.
2. Previous treatment with a PD-1, PD-L1, PD-L2, CTLA-4 inhibitor, or any other agents targeting T-cell co-stimulation or immune checkpoint pathways for unresectable or metastatic melanoma.
3. Recipient of solid organ transplant.
4. History of a cardiovascular illness including: congestive heart failure (New York Heart Association Grade III or IV); unstable angina or myocardial infarction within the previous 6 months prior to first dose of Study Treatment; or symptomatic cardiac arrhythmia despite medical management. QT interval corrected by heart rate using QTcF >450 ms in males or >470 ms in females, or congenital long QT syndrome.
5. Uncontrolled hypertension, systolic blood pressure (SBP) >160 mmHg or diastolic blood pressure (DBP) >100 mmHg.
6. Patients with new, active, or progressive brain metastases or leptomeningeal disease with except when considered for a separate special open-label cohort.
7. History of hemorrhagic diarrhea, inflammatory bowel disease, active uncontrolled peptic ulcer, or bowel resection that affects absorption of orally administered drugs.
8. Active, known, or suspected autoimmune disease, except for Type I diabetes mellitus, hypothyroidism requiring only hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic therapy.
9. Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.
10. Known history of testing positive for HIV, known AIDS.
11. Hepatitis B surface antigen positive or hepatitis C antibody positive. Further investigation per institutional practices may be performed to exclude active infection.
12. Patients with a condition requiring chronic systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days before administration of Study Treatment. Inhaled or topical steroids, or adrenal replacement dose of corticosteroids at dose = 10 mg/day prednisone equivalent are permitted.
13. Use of another investigational agent (drug or vaccine not marketed for any indication) within 28 days or before administration of Study Treatment. If the investigational agent is a monoclonal antibody then within 3 months before administration of Study Treatment
14. Pregnant or breast-feeding women.
15. Have a history of any other malignancy unless in remission for 2 years or locally curable cancers that have been treated with curative intent with no evidence of recurrence, such as:

* Basal or squamous cell skin cancer
* Superficial bladder cancer
* Carcinoma in situ of cervix or breast
* Incidental prostate cancer
* Non melanomatous skin cancer
* Prostate cancer treated with curative intent with serum prostate specific antigen (PSA) < 2.0 ng/mL
16. Patients with medical conditions requiring administration of strong cytochrome P450 (CYP), CYP3A4 Inducers and Inhibitors with no alternative therapy.
17. Uncontrolled adrenal insufficiency or active chronic liver disease.
18. Has received approved live vaccine/live attenuated vaccines within 30 days of planned Cycle 1 Day 1. Inactivated viral vaccines or vaccines based upon subviral component are allowed; however intranasal influenza vaccines (e.g. Flu-Mist) are not allowed. COVID-19 vaccination should be administered at least 7 days before Cycle 1 Day 1.
19. Underlying medical conditions that, in the Investigator's opinion, will make the administration of Study Treatment hazardous or obscure the interpretation of toxicity determination or AEs.
20. Patients with a history of or active interstitial lung disease (ILD) or non-infectious pneumonitis.
21. Patients with prior organ or hematopoietic cell transplant (HCT), including allogeneic HCT.
22. Patients with known sensitivity to any of the ingredients of the Study Treatment.
23. Patients who received radiation therapy within 14 days of the first dose of the Study Treatment.
24. Patients who take drugs that prolong the QT interval or cause torsades de pointes or produce significant ventricular dysrhythmias.
25. Patients that are unwilling or unable to comply with procedures required in this protocol.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/08/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2025
Actual
Sample size
Target
Accrual to date
Final
450
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Sydney Adventist Hospital - Wahroonga
Recruitment hospital [2] 0 0
University of the Sunshine Coast - Buderim
Recruitment hospital [3] 0 0
Icon Cancer Centre Wesley - South Brisbane
Recruitment hospital [4] 0 0
Ballarat Health Services - Ballarat
Recruitment hospital [5] 0 0
Goulburn Valley Health - Shepparton
Recruitment hospital [6] 0 0
Royal Brisband and Women's Hospital - Brisbane
Recruitment hospital [7] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [8] 0 0
Affinity Clinical Research - Nedlands
Recruitment hospital [9] 0 0
Tweed Hospital - Tweed Heads
Recruitment hospital [10] 0 0
Calvary Mater Newcastle - Waratah
Recruitment postcode(s) [1] 0 0
- Wahroonga
Recruitment postcode(s) [2] 0 0
4556 - Buderim
Recruitment postcode(s) [3] 0 0
- South Brisbane
Recruitment postcode(s) [4] 0 0
- Ballarat
Recruitment postcode(s) [5] 0 0
- Shepparton
Recruitment postcode(s) [6] 0 0
- Brisbane
Recruitment postcode(s) [7] 0 0
- Liverpool
Recruitment postcode(s) [8] 0 0
- Nedlands
Recruitment postcode(s) [9] 0 0
- Tweed Heads
Recruitment postcode(s) [10] 0 0
- Waratah
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
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United States of America
State/province [4] 0 0
Kentucky
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United States of America
State/province [5] 0 0
Maryland
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United States of America
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Missouri
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United States of America
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Montana
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United States of America
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North Carolina
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United States of America
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Ohio
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United States of America
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Pennsylvania
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United States of America
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South Carolina
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Texas
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Utah
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United States of America
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Virginia
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United States of America
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Wisconsin
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Austria
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Graz
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Austria
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Innsbruck
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Belgium
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Brasschaat
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Belgium
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Brussels
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Belgium
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Ghent
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Belgium
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Hasselt
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Belgium
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Liège
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Belgium
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Ottignies
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Brazil
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Bahia
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Brazil
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Paraná
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Brazil
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Rio Grande Do Sul
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Brazil
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Sao Paulo
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Brazil
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São Paulo,
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Brazil
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São Paulo
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Czechia
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Olomouc
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Czechia
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Ostrava-Poruba
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Czechia
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Prague
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France
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Besançon
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France
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Boulogne-Billancourt
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France
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Dijon
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France
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La Tronche
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Lille
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France
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Marseille
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France
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Paris
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France
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Pierre-Bénite
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France
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Rouen
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France
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Villejuif
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Germany
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Berlin
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Germany
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Dresden,
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Germany
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Erfurt
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Germany
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Essen
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Germany
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Freiburg
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Germany
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Heidelberg
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Germany
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Koeln
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Leipzig
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Germany
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Luebeck
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Germany
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Mainz
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Germany
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Mannheim
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Germany
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Tuebingen
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Italy
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Milano
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Italy
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Bari
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Italy
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Bologna
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Italy
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Misterbianco
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Italy
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Napoli
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Italy
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Palermo
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Italy
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Perugia
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Italy
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Roma
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Italy
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Siena
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Italy
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Verona
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Japan
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Nagano
Country [66] 0 0
Japan
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Osaka
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Japan
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Sunto-gun
Country [68] 0 0
Japan
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Tokho
Country [69] 0 0
Japan
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Fukuoka
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Japan
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Niigata
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Japan
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Okayama
Country [72] 0 0
Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
State/province [73] 0 0
Gyeonggi
Country [74] 0 0
Korea, Republic of
State/province [74] 0 0
Jeollanam-do
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Korea, Republic of
State/province [75] 0 0
Jung-gu
Country [76] 0 0
Korea, Republic of
State/province [76] 0 0
Seoul
Country [77] 0 0
New Zealand
State/province [77] 0 0
Auckland
Country [78] 0 0
New Zealand
State/province [78] 0 0
Hamilton
Country [79] 0 0
New Zealand
State/province [79] 0 0
Tauranga
Country [80] 0 0
Puerto Rico
State/province [80] 0 0
Rio Piedras
Country [81] 0 0
Singapore
State/province [81] 0 0
Singapore
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South Africa
State/province [82] 0 0
Gauteng
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South Africa
State/province [83] 0 0
Western Cape
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Spain
State/province [84] 0 0
Barcelona
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Spain
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Madrid
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Spain
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Málaga
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Spain
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Sevilla
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Spain
State/province [88] 0 0
Zaragoza
Country [89] 0 0
United Kingdom
State/province [89] 0 0
Hampshire
Country [90] 0 0
United Kingdom
State/province [90] 0 0
Edinburgh

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
HUYABIO International, LLC.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Bristol-Myers Squibb
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Gloria Lee, MD, PhD
Address 0 0
HUYABIO International, LLC.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
M Tawashi
Address 0 0
Country 0 0
Phone 0 0
1-858-209-1695
Fax 0 0
Email 0 0
mtawashi@huyabio.com
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT04674683