Gemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) in Participants With 1L BTC

A Phase II/III, Multicenter, Randomized, Placebo-controlled Study of Gemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) as First-line Treatment of Biliary Tract Cancer

Study consisted of an open-label, safety run-in part and a randomized, double-blind, placebo-controlled Phase 2/3 part. In the Phase 2/3 part, the study was evaluated whether bintrafusp alfa in combination with the current standard of care (SoC) (gemcitabine plus cisplatin) improves overall survival (OS) in chemotherapy and immunotherapy-naïve participants with locally advanced or metastatic Biliary Tract Cancer (BTC) compared to placebo, gemcitabine and cisplatin.

Study Overview

• Status: Terminated
• Conditions: Cholangiocarcinoma; Biliary Tract Cancer; Gallbladder Cancer
• Intervention / Treatment: Drug: M7824; Drug: Gemcitabine; Drug: Cisplatin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 309
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma Buenos Aires, Argentina
    • Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo
  • Ciudad Autonoma Buenos Aires, Argentina
    • Instituto de Investigaciones Metabolicas (IDIM)
  • Ciudad Autonoma Buenos Aires, Argentina
    • Instituto Médico Especializado Alexander Fleming
  • La Rioja, Argentina
    • Centro Oncologico Riojano Integral (CORI)
  • Salta, Argentina
    • CEDIT
  • San Miguel de Tucuman, Argentina
    • Centro Medico San Roque S.R.L.
  • San Salvador de Jujuy, Argentina
    • Fundacion Ars Medica
• Australia
  • Blacktown, Australia
    • Blacktown Hospital - PARENT
  • Clayton, Australia
    • Monash Health
  • Melbourne, Australia
    • Epworth Freemasons
  • South Brisbane, Australia
    • Icon Cancer Care South Brisbane
• Brazil
  • Barretos, Brazil
    • Hospital de Cancer de Barretos - Fundacao Pio XII
  • Rio de Janeiro, Brazil
    • INCA - Instituto Nacional de Cancer
  • Santo André, Brazil
    • CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
  • Sao Jose Rio Preto, Brazil
    • Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto
  • São Paulo, Brazil
    • A. C. Camargo Cancer Center
  • São Paulo, Brazil
    • ICESP - Instituto do Cancer do Estado de Sao Paulo Octavio Frias de Oliveira
• Chile
  • La Serena, Chile
    • IC La Serena Research
  • Santiago, Chile
    • Centro de Investigacion Clinica Bradford Hill
  • Santiago, Chile
    • Hospital Clinico Universidad de Chile
  • Santiago, Chile
    • PROSALUD
  • Temuco, Chile
    • Instituto Clinico Oncologico del Sur (ICOS)
• China
  • Beijing, China
    • Beijing Cancer Hospital
  • Beijing, China
    • Beijing Friendship Hospital, Capital Medical University
  • Beijing, China
    • Beijing Chao Yang Hospital
  • Chengdu, China
    • West China Hospital, Sichuan University
  • Hangzhou, China
    • Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine
  • Qingdao, China
    • The Affiliated Hospital of Qingdao University
  • Shanghai, China
    • Fudan University Shanghai Cancer Hospital
  • Suzhou, China
    • The Second Affiliated Hospital of Soochow University
  • Tianjin, China
    • Tianjin Medical University Cancer Institute & Hospital
  • Wuhan, China
    • Union Hospital Tongji Medical College Huazhong University of Science and Technology
• France
  • Angers Cedex 2, France
    • ICO - Site Paul Papin - service d'oncologie medicale
  • Dijon cedex, France
    • Centre Georges François Leclerc - Oncologie Médicale
  • Lille cedex, France
    • CHU Lille - Hôpital Claude Huriez
  • Saint Herblain, France
    • ICO - Site René Gauducheau
  • Toulouse Cedex 9, France
    • CHU de Toulouse - Hôpital Ranguei
• Germany
  • Berlin, Germany
    • Vivantes Klinikum Neukoelln - Haematologie und Onkologie
  • Bonn, Germany
    • Universitaetsklinikum Bonn AoeR - Medizinische Klinik I Gastroenterologie
  • Dresden, Germany
    • Universitaetsklinikum Carl Gustav Carus TU Dresden - Medizinische Klinik I
  • Frankfurt, Germany
    • Klinikum der Johann Wolfgang Goethe-Universitaet
  • Mainz, Germany
    • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz - Medizinische Klinik I - HCC Ambulanz
• Italy
  • Milano, Italy
    • Fondazione IRCCS Istituto Nazionale dei Tumori Milano
  • Padova, Italy
    • IOV - Istituto Oncologico Veneto IRCCS - S.Semplice Dip.Oncologia dei Melanomi
  • Roma, Italy
    • Università Campus Bio-Medico di Roma
  • Verona, Italy
    • Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma) - UOC Oncologia
• Japan
  • Chiba-shi, Japan
    • Chiba Cancer Center
  • Chuo-ku, Japan
    • National Cancer Center Hospital - Dept of Hepatobiliary and Pancreatic Oncology
  • Fukuoka-shi, Japan
    • NHO Kyushu Cancer Center - Dept of Gastroenterology/Hepatology/Pancreatology
  • Kashiwa-shi, Japan
    • National Cancer Center Hospital East
  • Koto-ku, Japan
    • Cancer Institute Hospital of JFCR - Dept of Hepato,Biliary and Pancreatic Medicine
  • Mitaka-shi, Japan
    • Kyorin University Hospital
  • Nagoya-shi, Japan
    • Aichi Cancer Center Hospital
  • Osaka-shi, Japan
    • Osaka City University Hospital
  • Osakasayama-shi, Japan
    • Kindai University Hospital
  • Yokohama-shi, Japan
    • Kanagawa Cancer Center
• Korea, Republic of
  • Daejeon, Korea, Republic of
    • Chungnam National University Hospital - Department of Internal Medicine (Rheumatology)
  • Seongnam-si, Korea, Republic of
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of
    • The Catholic University of Korea, Seoul St. Mary's Hospital
• Poland
  • Gliwice, Poland
    • Centrum Onkologii-Instytut im.M.Sklodowskiej Curie
  • Krakow, Poland
    • Pratia
  • Warszawa, Poland
    • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
  • Zamosc, Poland
    • ETG Zamosc
• Spain
  • Barcelona, Spain
    • Hospital Clinic i Provincial de Barcelona - Servicio de Oncologia
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron - Dept of Oncology
  • Caceres, Spain
    • Hospital San Pedro de Alcantara - Servicio de Oncologia
  • Cordoba, Spain
    • Hospital Universitario Reina Sofia - Dept of Oncology
  • L'Hospitalet de Llobregat, Spain
    • ICO l´Hospitalet - Hospital Duran i Reynals
  • Madrid, Spain
    • Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
  • Madrid, Spain
    • Hospital Universitario Clinico San Carlos - Servicio de Oncologia
  • Madrid, Spain
    • Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia
  • Valencia, Spain
    • Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica
  • Valencia, Spain
    • Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica
• Taiwan
  • Kaohsiung, Taiwan
    • Kaohsiung Chang Gung Memorial Hospital
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taichung, Taiwan
    • Taichung Veterans General Hospital
  • Tainan, Taiwan
    • National Cheng Kung University Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan
    • Chang Gung Memorial Hospital, Linkou
• United Kingdom
  • Manchester, United Kingdom
    • The Christie - Dept of Oncology
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Ironwood Cancer & Research Centers - Chandler II
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic in Florida - Department of Neurology
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center
  • Kansas
    • Westwood, Kansas, United States, 66216
      • University of Kansas Medical Center Research Institute, Inc. - University of Kansas Cancer Center/Bloch Pavilion
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Sidney Kimmel Comprehensive Cancer Center at John Hopkins
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • Texas
    • Dallas, Texas, United States, 75203
      • Methodist Transplant Physicians
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center - Unit 429
    • The Woodlands, Texas, United States, 77380
      • Renovatio Clinical - CENTRAL SITE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Are participants with histologically or cytologically confirmed locally advanced or metastatic BTC
• Participants must have available tumor tissue (primary or metastatic) (archival or fresh biopsies) before the first administration of study treatment
• At least 1 measurable lesion according to RECIST 1.1
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 at study entry and at Week 1, Day 1 prior to dosing
• Life expectancy of >= 12 weeks, as judged by the Investigator
• Adequate hematological function, hepatic function, renal function, coagulation function as defined in the protocol
• Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive participants must be treated and on a stable dose of antivirals
• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Previous and/or intercurrent cancers
• Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression
• Participants with symptomatic central nervous system (CNS) metastases
• Significant acute or chronic infection including known history of positive test for human immunodeficiency virus (HIV), active tuberculosis, uncontrolled biliary infection and active bacterial or fungal infection requiring systemic therapy (with the exception of hepatitis B and hepatitis C) requiring systemic therapy at study entry and at Week 1 Day 1 prior to dosing.
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
• History of or concurrent interstitial lung disease
• History of hypersensitivity reactions to bintrafusp alfa, anaphylaxis, or recent (within 5 months) uncontrolled asthma, cardiovascular/cerebrovascular disease
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before randomization
• Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune checkpoints)
• Other protocol defined exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Safety Run-In Part: M7824 + Gemcitabine + Cisplatin	Drug: M7824; Participants received intravenous infusion of M7824 at a dose of 2400 milligrams (mg), once every 3 weeks (Q3W) 2 years (in case of Complete Response), otherwise until criterion pre-sepcified in protocol for discontinuation is met, in combination with intravenous infusion of Gemcitabine and Cisplatin at a dose of 1000 milligram per meter square (mg/m^2) and 25 mg/m^2 respectively on Day 1 and Day 8 of 21- day cycle, for 8 cycles every 3 weeks.; Drug: Gemcitabine; Gemcitabine was received intravenously at a dose of 1000 milligram per meter square (mg/m^2) on Day 1 and Day 8 of 21- day cycle, for 8 cycles every 3 weeks (Q3W).; Drug: Cisplatin; Cisplatin was received intravenously at a dose of 25 mg/m^2 on Day 1 and Day 8 of 21-day cycle, for 8 cycles every 3 weeks (Q3W).
Experimental: Double-blinded Part: M7824 + Gemcitabine + Cisplatin	Drug: M7824; Participants received intravenous infusion of M7824 at a dose of 2400 milligrams (mg), once every 3 weeks (Q3W) 2 years (in case of Complete Response), otherwise until criterion pre-sepcified in protocol for discontinuation is met, in combination with intravenous infusion of Gemcitabine and Cisplatin at a dose of 1000 milligram per meter square (mg/m^2) and 25 mg/m^2 respectively on Day 1 and Day 8 of 21- day cycle, for 8 cycles every 3 weeks.; Drug: Gemcitabine; Gemcitabine was received intravenously at a dose of 1000 milligram per meter square (mg/m^2) on Day 1 and Day 8 of 21- day cycle, for 8 cycles every 3 weeks (Q3W).; Drug: Cisplatin; Cisplatin was received intravenously at a dose of 25 mg/m^2 on Day 1 and Day 8 of 21-day cycle, for 8 cycles every 3 weeks (Q3W).
Placebo Comparator: Double-blinded Part: Placebo + Gemcitabine + Cisplatin	Drug: Gemcitabine; Gemcitabine was received intravenously at a dose of 1000 milligram per meter square (mg/m^2) on Day 1 and Day 8 of 21- day cycle, for 8 cycles every 3 weeks (Q3W).; Drug: Cisplatin; Cisplatin was received intravenously at a dose of 25 mg/m^2 on Day 1 and Day 8 of 21-day cycle, for 8 cycles every 3 weeks (Q3W).; Drug: Placebo; Participants received intravenous infusion of M7824 matched placebo, once every 3 weeks (Q3W) until 2 years (in case of CR), otherwise until crtiterion pre-sepcified in protocol for discontinuation is met.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Run-in Part: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)	A DLT is a toxicity related to the study intervention that meets the following criteria as evaluated in the open-label, safety run-in: Grade 3 or 4 Immune-related adverse event (irAE) that needs permanent discontinuation of M7824 treatment; a malignant skin lesion induced by M7824 that is local and can be resected with a negative resection margin is not a DLT; Grade 3 or 4 nonhematologic toxicity other than irAE, A life threatening hematological toxicity (unless clearly attributable to chemotherapy alone), which is hardly medically manageable, including a bleeding event resulting in urgent intervention and admission to an intensive care unit and Grade 5 toxicity.	Day 1 up to Day 21 of Cycle 1 (each Cycle is of 21 days)
Double-blind Part: Overall Survival	Overall Survival was defined as the time from study day 1 to the date of death due to any cause. The overall survival was analyzed by using the Kaplan-Meier method.	Time from study day 1 up to data cutoff (assessed up to 609 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Double-blind Part: Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)	Percentage of participants with confirmed objective response that is at least one overall assessment of complete response (CR) or partial response (PR) reported here. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Confirmed CR = at least 2 determinations of CR at least 4 weeks apart and before progression. Confirmed PR = at least 2 determinations of PR at least 4 weeks apart and before progression (and not qualifying for a CR). Confirmed objective response was determined according to RECIST v1.1 and as adjudicated by IRC.	Time from randomization of study drug up to data cut off (assessed up to 609 days)
Safety Run-in Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (SAEs) and Treatment Related TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0	Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAE was defined as events with onset date or worsening during the on treatment period. TEAEs included serious TEAEs and non-serious TEAEs.	Time from first treatment up to data cutoff (assessed up to 609 days)
Safety Run-in Part: Number of Participants With Grade Greater Than or Equal (>=) 3 Laboratory Abnormalities	Laboratory investigation included hematology and biochemistry. The number of participants with Grade >=3 laboratory abnormalities were reported. Severity of grade 3 or higher TEAEs were graded using NCI-CTCAE v5.0 toxicity grades, as follows: Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death.	Time from first treatment up to data cutoff (assessed up to 609 days)
Double-blind Part: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)	Progression free survival was defined as the time from randomization of study intervention until the first documentation of disease progression (PD) or death due to any cause in the absence of documented PD, whichever occurred first. PD: At least a 20 percent (%) increase in the sum of the longest diameter (SLD) taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.	Time from randomization of study drug until the first documentation of PD or death, assessed up to 609 days
Double-blind Part: Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)	DOR was defined for participants with objective response, as the time from first documentation of objective response (confirmed Complete Response [CR] or Partial Response [PR]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DOR was determined according to RECIST v1.1 and assessed by IRC. Results were calculated based on Kaplan-Meier estimates.	From first documented objective response to PD or death due to any cause, assessed up to 609 days
Double-blind Part: Durable Response of at Least 6 Months According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator	Durable Response was defined as the number of participants with confirmed objective response (CR or PR) according to RECIST 1.1, determined by Investigator with duration of at least 6 months. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions.	Time from first treatment assessed up to 1148 days
Double-blind Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs (SAEs), Treatment Related TEAEs and Adverse Events of Special Interest (AESIs) According to NCI-CTCAE Version 5.0	AE was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAE was defined as events with onset date or worsening during the on treatment period. TEAEs included serious TEAEs and non-serious TEAEs. Adverse events of special interest (AESI) are serious or non-serious AEs that are of clinical interest and should be closely followed. For this study, AESIs include the following: Infusion-related reactions including immediate hypersensitivity; Immune-related AEs; Transforming growth factor beta (TGFβ) inhibition mediated skin reactions; Anemia; Bleeding AEs.	Time from first treatment up to data cutoff (assessed up to 609 days)

Collaborators and Investigators

• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborators: Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

General Publications

• Yoo C, Oh DY, Choi HJ, Kudo M, Ueno M, Kondo S, Chen LT, Osada M, Helwig C, Dussault I, Ikeda M. Phase I study of bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1, in patients with pretreated biliary tract cancer. J Immunother Cancer. 2020 May;8(1):e000564. doi: 10.1136/jitc-2020-000564.

Helpful Links

• US Medical Information website, Medical Resources
• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2019
• Primary Completion (Actual): May 20, 2021
• Study Completion (Actual): November 10, 2022

Study Registration Dates

• First Submitted: August 22, 2019
• First Submitted That Met QC Criteria: August 22, 2019
• First Posted (Actual): August 26, 2019

Study Record Updates

• Last Update Posted (Estimated): November 14, 2023
• Last Update Submitted That Met QC Criteria: October 26, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Cholangiocarcinoma; M7824; Metastatic Biliary Tract Cancer; Gallbladder Cancer; Ampullary cancer; Bintrafusp alfa; Transforming growth factor-beta; Programmed death-ligand 1
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Gallbladder Diseases; Biliary Tract Diseases; Cholangiocarcinoma; Biliary Tract Neoplasms; Gallbladder Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Gemcitabine
• Other Study ID Numbers: MS200647_0055; 2019-001992-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
• IPD Sharing Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union.
• IPD Sharing Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No