SC Versus IV Isatuximab in Combination With Pomalidomide and Dexamethasone in RRMM
- Conditions
- Plasma Cell Myeloma Recurrent
- Interventions
- Registration Number
- NCT05405166
- Lead Sponsor
- Sanofi
- Brief Summary
This is a randomized, multicenter, Phase 3, open-label study evaluating subcutaneous (SC) vs intravenous (IV) administration of isatuximab in combination with pomalidomide and dexamethasone (Pd) in RRMM patients (study participants) who have received at least 1 prior line of therapy including lenalidomide and a proteasome inhibitor (PI). Eligible participants will be randomized 1:1 into 1 of 2 study arms:
Arm SC: Isatuximab SC + Pd
Arm IV: Isatuximab IV + Pd
Participants will be allowed to continue therapy until disease progression, unacceptable adverse events (AEs), participant request to discontinue therapy or any other reason, whichever comes first.
- Detailed Description
Two study arms will be treated in 4-week cycles until disease progression, unacceptable adverse events (AEs), participant request to discontinue therapy or any other reason, whichever comes first.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 531
- Participants with multiple myeloma who have received at least one prior line of anti-myeloma therapy, which must include lenalidomide and a proteasome inhibitor given alone or in combination.
- Measurable serum M-protein (≥ 0.5 g/dL) and/or urine M-protein (≥ 200 mg/24 hours) and/or serum free light chain (FLC) assay (Involved FLC assay ≥10 mg/dL and abnormal serum FLC ratio (<0.26 or >1.65)).
- Primary refractory multiple myeloma participants
- Participants with prior anti-CD38 treatment: (a) administered less than 9 months before randomization or, (b) intolerant to the anti-CD38 previously received
- Prior therapy with pomalidomide
- Participants with inadequate biological tests.
- Significant cardiac dysfunction
- Participants diagnosed or treated for another malignancy within 3 years prior to randomization with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, and in situ malignancy, or low risk prostate cancer after curative therapy
- Concomitant plasma cell leukemia
- Active primary amyloid light -chain amyloidosis
- Known acquired immunodeficiency syndrome (AIDS)-related illness or known human immunodeficiency virus (HIV) disease requiring antiviral treatment
- Know active Hepatitis A infection. Current active or chronic hepatitis B (HBV) or hepatitis C (HCV) infection. Participants with chronic HBV or HCV disease that is controlled under antiviral therapy are allowed.
- Women of childbearing potential or male participant with women of childbearing potential who do not agree to use highly effective method of birth control
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Isatuximab Subcutaneous (SC) Isatuximab SC Isatuximab dose will be administered SC weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days in duration. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication. Isatuximab Subcutaneous (SC) Paracetamol / Acetaminophen Isatuximab dose will be administered SC weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days in duration. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication. Isatuximab Intravenous (IV) Isatuximab IV Isatuximab dose will be administered via IV infusion weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication. Isatuximab Intravenous (IV) Paracetamol / Acetaminophen Isatuximab dose will be administered via IV infusion weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication. Isatuximab Subcutaneous (SC) Dexamethasone Isatuximab dose will be administered SC weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days in duration. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication. Isatuximab Subcutaneous (SC) Pomalidomide Isatuximab dose will be administered SC weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days in duration. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication. Isatuximab Subcutaneous (SC) Montelukast Isatuximab dose will be administered SC weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days in duration. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication. Isatuximab Subcutaneous (SC) Diphenhydramine Isatuximab dose will be administered SC weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days in duration. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication. Isatuximab Subcutaneous (SC) Methylprednisolone Isatuximab dose will be administered SC weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days in duration. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication. Isatuximab Intravenous (IV) Pomalidomide Isatuximab dose will be administered via IV infusion weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication. Isatuximab Intravenous (IV) Montelukast Isatuximab dose will be administered via IV infusion weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication. Isatuximab Intravenous (IV) Dexamethasone Isatuximab dose will be administered via IV infusion weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication. Isatuximab Intravenous (IV) Diphenhydramine Isatuximab dose will be administered via IV infusion weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication. Isatuximab Intravenous (IV) Methylprednisolone Isatuximab dose will be administered via IV infusion weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication.
- Primary Outcome Measures
Name Time Method Overall response rate (ORR) Up to approximately 2 years ORR defined as the proportion of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) according to the 2016 IMWG criteria assessed by Independent Review Committee (IRC).
Observed concentration before dosing (Cthrough) at steady state Predose at Cycle 6 Day 1 (duration of each cycle is 28 days) Observed Isatuximab plasma concentration
- Secondary Outcome Measures
Name Time Method Observed concentration before dosing (Ctrough) At 4 weeks i.e., predose at Cycle 2 Day 1 (duration of each cycle is 28 days) Observed Isatuximab plasma concentration
Incidence rate of infusion-reactions Up to approximately 4 years Proportion of participants with infusion-reactions related events
Percentage of participants satisfied or very satisfied with the injection method used to administer study medication At Cycle 5 Day 15 Participant's satisfaction with isatuximab subcutaneous (SC) and intravenous (IV) will be assessed based on the Patient Experience and Satisfaction Questionnaires (PESQ) questionnaire.
Duration of response (DOR) Up to approximately 2 years DOR, defined as the time from the date of the first confirmed response to the date of first occurrence of progressive disease (PD) as determined by IRC or death, whichever happens first. DOR is determined only for participants who have achieved a response (PR or better). In the absence of PD or death before the analysis cut-off date, the DOR will be censored at the date of the last valid disease assessment performed prior to initiation of a further anti-myeloma treatment or the analysis cut-off date, whichever is earlier. Participants with two or more consecutive missed assessments prior to PD or death will be censored at the last valid disease assessment.
Time to first response (TT1R) Up to approximately 2 years TT1R, defined as the time from randomization to the date of first IRC determined response (PR or better) that is subsequently confirmed. Same censoring rule applies as in the DOR endpoint.
Time to best response (TTBR) Up to approximately 2 years TTBR, defined as the time from randomization to the date of first occurrence of IRC determined best overall response (PR or better) that is subsequently confirmed. Same censoring rule applies as in the DOR endpoint
Progression free survival (PFS) Up to approximately 4 years PFS, defined as the time from the date of randomization to the date of first documentation of progressive disease as determined by IRC or the date of death from any cause, whichever comes first. Responses will be determined according to IMWG criteria. Progression based on paraprotein will be confirmed based on two consecutive assessments. PFS will be censored at the date of the last valid disease assessment not showing disease progression performed prior to initiation of a further anti-myeloma treatment (if any) or the analysis cut-off date, whichever comes first. Participants with two or more consecutive missed assessments prior to PD or death will be censored at the last valid disease assessment.
Overall survival (OS) Up to approximately 4 years OS, defined as the time from the date of randomization to death from any cause. Participants without death prior to the analysis cut-off date will be censored at the last date the participant was known to be alive or the cut-off date, whichever is first.
Progression free survival 2 (PFS2) Up to approximately 4 years PFS2, defined as time from the date of randomization to the date of first documentation of PD (as assessed by investigator) after initiation of further anti-myeloma treatment or death from any cause, whichever happens first. Same censoring rule applies as in the PFS endpoint.
Number of participants with treatment-emergent adverse events (TEAEs)/serious adverse events (SAEs). Up to approximately 4 years Treatment-emergent adverse events (AEs) are defined as AEs that develop, worsen (according to the Investigator opinion), or become serious during the treatment period. The treatment period is defined as the time from first dose of study treatment up to 30 days after last dose of study treatment.
Very Good Partial Response or better rate (VGPR) Up to approximately 2 years Very Good Partial Response or better rate defined as the proportion of participants with stringent complete response (sCR), complete response (CR) and very good partial response (VGPR) according to the 2016 International Myeloma Working Group (IMWG) criteria assessed by Independent Review Committee (IRC).
Pharmacokinetic (PK) parameter Up to approximately 4 years Maximum plasma concentration (Cmax)
PK parameter Up to approximately 4 years Area under the plasma concentration time curve over the dosing period (AUC)
Successful injection rate Up to approximately 4 years Number of successful injections with (investigational) isatuximab injector device divided by total number of actual injections
Percentage of participants with anti-drug antibodies (ADA) against isatuximab Up to approximately 4 years An ADA positive patient was defined as a subject either having treatment-induced ADA response (no positive ADA response at baseline and any positive response in the post baseline period, including the follow-up visit) or a treatment-boosted ADA response (a positive ADA response at baseline and a ≥4-fold increase in titer in the post baseline period including the follow-up visit).
Participant expectation questionnaire-baseline (PEQ-BL) score Cycle 1 Day 1 ((duration of each cycle is 28 days) PEQ-BL is designed to assess the expectations of the participants regarding both the treatment (side effects, worth taking) and the administration method (confidence, comfortability, pain, side effects, potential time-savings), as well as to understand previous treatment experience from the participant (experience with injection methods for oncology medication).
Patient experience and satisfaction questionnaire- follow up (PESQ-FU) score Up to approximately 4 years PESQ-FU, a 9-item questionnaire is designed to follow up on participant experience and satisfaction regarding the treatment (side effects, worth taking and overall satisfaction) and the administration method (confidence, comfortability, pain, side effects, potential time-savings and overall satisfaction).
Patient experience and satisfaction questionnaire-end of treatment (PESQ-EOT) score Up to approximately 4 years PESQ-EOT, a 17-item questionnaire is designed to assess participant experience and satisfaction regarding the treatment (side effects, worth taking and overall satisfaction) and the administration method (confidence, comfortability, pain, side effects, potential time-savings and overall satisfaction). This questionnaire includes also additional items to assess participant preference on injection method (subcutaneous or intravenous) and location of administration (at home or at clinic).
Patient's Assessment of Treatment (PAT) questionnaire score Up to approximately 4 years The PAT provides patient insights on the benefits and disadvantages of treatment, including an overall Benefit/Disadvantage ratio using a final question that provides a quantitative assessment of the patient's perceived B/D. The 4-item PAT is an internally developed non-disease specific and self-administered assessment. This questionnaire contains 4 items and take approximately 2-3 minutes to complete.
Change from baseline in the Health Resource Utilization and Productivity Questionnaire (HRUPQ) scores Baseline; up to approximately 4 years Medical resource utilization and participant productivity will be collected from participants through the HRUPQ questionnaire. The questions include number, nature (emergency or routine) and duration of hospitalizations; emergency room visits and outpatient medical encounters; and employment history. The HRUPQ contains 46 items.
Change from baseline in European Organization for Research and Treatment of Cancer core quality of life questionnaire (EORTC QLQ-C30) score Baseline; up to approximately 4 years EORTC QLQ-C30 is a cancer-specific questionnaire that contains 30 items and provides a multidimensional assessment of Health Related Quality of Life (HRQL).
Change from baseline in European Organization for Research and Treatment of Cancer quality of life myeloma module (EORTC QLQ-MY20) Baseline; up to approximately 4 years EORTC QLQ-MY20, a 20-item questionnaire is used to assess symptoms and side effects due to the treatment or the disease which impact HRQL in participants with multiple myeloma.
Change from baseline in the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L) scores Baseline; up to approximately 4 years EQ-5D-5L questionnaire is a measure of health status that provides a simple, generic measure of health utility, and consists of 2 sections: descriptive and visual analogue scale (VAS). The descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The VAS records the respondent's self-rated health on a 20 cm vertical, VAS with endpoints labelled 'the best health you can imagine' and 'the worst health you can imagine.'
Number of participants with chromosomal abnormalities Up to approximately 4 years Explore chromosomal abnormalities (mainly but not limited to t(4;14), t(14;16), del(17p), and 1q21+)
Trial Locations
- Locations (146)
Arizona Oncology Associates, PC - HAL- Site Number : 8400015
🇺🇸Prescott Valley, Arizona, United States
Rocky Mountain Cancer Centers, LLP- Site Number : 8400021
🇺🇸Aurora, Colorado, United States
Mayo Clinic- Site Number : 8400008
🇺🇸Jacksonville, Florida, United States
Centre for Cancer and Blood Disorders- Site Number : 8400026
🇺🇸Bethesda, Maryland, United States
Comprehensive Cancer Centers of Nevada- Site Number : 8400019
🇺🇸Las Vegas, Nevada, United States
New York Oncology Hematology, P.C.- Site Number : 8400017
🇺🇸Albany, New York, United States
Novant Health- Site Number : 8400014
🇺🇸Charlotte, North Carolina, United States
Oncology_Hematology Care Clinical Trials, LLC- Site Number : 8400016
🇺🇸Cincinnati, Ohio, United States
Oncology Associates Of Oregon, P.C.- Site Number : 8400018
🇺🇸Eugene, Oregon, United States
Gibbs Cancer Center-Spartanburg Medical Center- Site Number : 8400002
🇺🇸Spartanburg, South Carolina, United States
Texas Oncology Baylor Sammons- Site Number : 8400022
🇺🇸Dallas, Texas, United States
University of Texas Southwestern- Site Number : 8400024
🇺🇸Dallas, Texas, United States
Lumi Research- Site Number : 8400029
🇺🇸Kingwood, Texas, United States
Texas Oncology - San Antonio- Site Number : 8400020
🇺🇸San Antonio, Texas, United States
George E. Wahlen Salt Lake City VA Medical Center- Site Number : 8400011
🇺🇸Salt Lake City, Utah, United States
NOHC - Nucleo de Oncologia e Hematologia do Ceara- Site Number : 0760006
🇧🇷Fortaleza, Ceará, Brazil
Clínica São Germano- Site Number : 0760001
🇧🇷Sao Paulo, São Paulo, Brazil
Instituto COI de Educacao e Pesquisa- Site Number : 0760004
🇧🇷Rio De Janeiro, Brazil
Mohtaseb Cancer Center and Blood Disorders Site Number : 8400028
🇺🇸Bullhead City, Arizona, United States
BRCR Medical Center Inc Site Number : 8400030
🇺🇸Plantation, Florida, United States
Hattiesburg Clinic Site Number : 8400006
🇺🇸Hattiesburg, Mississippi, United States
Atlantic Health System Site Number : 8400005
🇺🇸Morristown, New Jersey, United States
Novant Health Forsyth Medical Center Site Number : 8400114
🇺🇸Winston-Salem, North Carolina, United States
Gabrail Cancer Center Site Number : 8400027
🇺🇸Canton, Ohio, United States
Spoknwrd Clinical Trials Inc. Site Number : 8400023
🇺🇸Easton, Pennsylvania, United States
UW Cancer Center at ProHealth Care Site Number : 8400001
🇺🇸Waukesha, Wisconsin, United States
Investigational Site Number : 0320007
🇦🇷Caba, Buenos Aires, Argentina
Investigational Site Number : 0320001
🇦🇷Caba, Buenos Aires, Argentina
Investigational Site Number : 0320002
🇦🇷Ciudad Autonoma Buenos Aires, Buenos Aires, Argentina
Investigational Site Number : 0320006
🇦🇷La Plata, Buenos Aires, Argentina
Investigational Site Number : 0320003
🇦🇷Caba, Ciudad De Buenos Aires, Argentina
Investigational Site Number : 0320008
🇦🇷Caba, Ciudad De Buenos Aires, Argentina
Investigational Site Number : 0320005
🇦🇷Caba, Ciudad De Buenos Aires, Argentina
Investigational Site Number : 0320010
🇦🇷Cordoba, Córdoba, Argentina
Investigational Site Number : 0320004
🇦🇷Buenos Aires, Argentina
Investigational Site Number : 0320009
🇦🇷Mendoza, Argentina
Investigational Site Number : 0360007
🇦🇺Liverpool, New South Wales, Australia
Investigational Site Number : 0360004
🇦🇺Waratah, New South Wales, Australia
Investigational Site Number : 0360003
🇦🇺Wollongong, New South Wales, Australia
Investigational Site Number : 0360008
🇦🇺Adelaide, South Australia, Australia
Investigational Site Number : 0360009
🇦🇺Fitzroy, Victoria, Australia
Investigational Site Number : 0360006
🇦🇺Melbourne, Victoria, Australia
Investigational Site Number : 0360001
🇦🇺Richmond, Victoria, Australia
OC ONCOCLINICAS MULTIHEMO ILHA DO LEITE Site Number : 0760007
🇧🇷Recife, Pernambuco, Brazil
CHN - Complexo Hospitalar de Niteroi Site Number : 0760008
🇧🇷Niteroi, Rio De Janeiro, Brazil
Hospital Mae de Deus Site Number : 0760003
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Investigational Site Number : 1240001
🇨🇦Toronto, Ontario, Canada
Investigational Site Number : 1240004
🇨🇦Greenfield Park, Quebec, Canada
Investigational Site Number : 1240003
🇨🇦Montreal, Quebec, Canada
Investigational Site Number : 1520003
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1520002
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1520006
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1520005
🇨🇱Viña del Mar, Valparaíso, Chile
Investigational Site Number : 1520004
🇨🇱Santiago, Chile
Investigational Site Number : 1520001
🇨🇱Temuco, Chile
Investigational Site Number : 1560001
🇨🇳Beijing, China
Investigational Site Number : 1560022
🇨🇳Beijing, China
Investigational Site Number : 1560010
🇨🇳Changsha, China
Investigational Site Number : 1560006
🇨🇳Guangzhou, China
Investigational Site Number : 1560002
🇨🇳Hangzhou, China
Investigational Site Number : 1560020
🇨🇳Nanchang, China
Investigational Site Number : 1560019
🇨🇳Nanning, China
Investigational Site Number : 1560011
🇨🇳Qingdao, China
Investigational Site Number : 1560013
🇨🇳Shenyang, China
Investigational Site Number : 1560007
🇨🇳Tianjin, China
Investigational Site Number : 1560009
🇨🇳Tianjin, China
Investigational Site Number : 1560018
🇨🇳Tianjin, China
Investigational Site Number : 1560003
🇨🇳Wuhan, China
Investigational Site Number : 1560008
🇨🇳Wuhan, China
Investigational Site Number : 1560004
🇨🇳Zhengzhou, China
Investigational Site Number : 2030005
🇨🇿Brno, Czechia
Investigational Site Number : 2030003
🇨🇿Olomouc, Czechia
Investigational Site Number : 2030006
🇨🇿Ostrava - Poruba, Czechia
Investigational Site Number : 2030004
🇨🇿Praha 2, Czechia
Investigational Site Number : 2500002
🇫🇷Nantes, France
Investigational Site Number : 2500005
🇫🇷Paris, France
Investigational Site Number : 2500008
🇫🇷Perigueux, France
Investigational Site Number : 2500001
🇫🇷Poitiers, France
Investigational Site Number : 2500009
🇫🇷Saint-Etienne Cedex 2, France
Investigational Site Number : 2500003
🇫🇷TOULOUSE Cedex 9, France
Investigational Site Number : 2500007
🇫🇷Tours, France
Investigational Site Number : 2760005
🇩🇪Dresden, Germany
Investigational Site Number : 2760001
🇩🇪Hamburg, Germany
Investigational Site Number : 2760003
🇩🇪Heidelberg, Germany
Investigational Site Number : 2760006
🇩🇪Lübeck, Germany
Investigational Site Number : 2760007
🇩🇪Nürnberg, Germany
Investigational Site Number : 3000002
🇬🇷Athens, Greece
Investigational Site Number : 3000001
🇬🇷Athens, Greece
Investigational Site Number : 3000005
🇬🇷Ioannina, Greece
Investigational Site Number : 3000003
🇬🇷Patra, Greece
Investigational Site Number : 3000004
🇬🇷Thessaloniki, Greece
Investigational Site Number : 3480002
🇭🇺Budapest, Hungary
Investigational Site Number : 3480004
🇭🇺Budapest, Hungary
Investigational Site Number : 3480003
🇭🇺Kaposvár, Hungary
Investigational Site Number : 3480008
🇭🇺Pécs, Hungary
Investigational Site Number : 3480005
🇭🇺Szekesfehervar, Hungary
Investigational Site Number : 3480006
🇭🇺Szombathely, Hungary
Investigational Site Number : 3800001
🇮🇹Meldola, Forlì-Cesena, Italy
Investigational Site Number : 3800006
🇮🇹Rome, Roma, Italy
Investigational Site Number : 3800004
🇮🇹Ancona, Italy
Investigational Site Number : 3800002
🇮🇹Bologna, Italy
Investigational Site Number : 3800005
🇮🇹Brescia, Italy
Investigational Site Number : 3800007
🇮🇹Napoli, Italy
Investigational Site Number : 3800008
🇮🇹Palermo, Italy
Investigational Site Number : 3800003
🇮🇹Pavia, Italy
Investigational Site Number : 3920001
🇯🇵Nagoya-shi, Aichi, Japan
Investigational Site Number : 3920007
🇯🇵Kamogawa-shi, Chiba, Japan
Investigational Site Number : 3920005
🇯🇵Higashiibaraki-gun, Ibaraki, Japan
Investigational Site Number : 3920010
🇯🇵Shiwa-gun, Iwate, Japan
Investigational Site Number : 3920012
🇯🇵Kamakura-shi, Kanagawa, Japan
Investigational Site Number : 3920003
🇯🇵Kyoto-shi, Kyoto, Japan
Investigational Site Number : 3920006
🇯🇵Natori-shi, Miyagi, Japan
Investigational Site Number : 3920002
🇯🇵Okayama-shi, Okayama, Japan
Investigational Site Number : 3920011
🇯🇵Osaka-shi, Osaka, Japan
Investigational Site Number : 3920008
🇯🇵Sunto-gun, Shizuoka, Japan
Investigational Site Number : 3920004
🇯🇵Shibuya-ku, Tokyo, Japan
Investigational Site Number : 3920009
🇯🇵Yamagata-shi, Japan
Investigational Site Number : 5780001
🇳🇴Oslo, Norway
Investigational Site Number : 5780002
🇳🇴Ålesund, Norway
Investigational Site Number : 6160004
🇵🇱Wroclaw, Dolnoslaskie, Poland
Investigational Site Number : 6160005
🇵🇱Krakow, Malopolskie, Poland
Investigational Site Number : 6160001
🇵🇱Lublin, Poland
Investigational Site Number : 7240003
🇪🇸Santander, Cantabria, Spain
Investigational Site Number : 7240004
🇪🇸Badalona, Catalunya [Cataluña], Spain
Investigational Site Number : 7240007
🇪🇸Madrid, Madrid, Comunidad De, Spain
Investigational Site Number : 7240001
🇪🇸Pamplona, Navarra, Spain
Investigational Site Number : 7240005
🇪🇸Madrid, Spain
Investigational Site Number : 7240006
🇪🇸Murcia, Spain
Investigational Site Number : 7240002
🇪🇸Salamanca, Spain
Investigational Site Number : 7520001
🇸🇪Borås, Sweden
Investigational Site Number : 7520003
🇸🇪Stockholm, Sweden
Investigational Site Number : 1580001
🇨🇳Kaohsiung, Taiwan
Investigational Site Number : 1580005
🇨🇳Tainan, Taiwan
Investigational Site Number : 1580002
🇨🇳Taipei, Taiwan
Investigational Site Number : 7920007
🇹🇷Ankara, Turkey
Investigational Site Number : 7920009
🇹🇷Ankara, Turkey
Investigational Site Number : 7920004
🇹🇷Bornova, Turkey
Investigational Site Number : 7920003
🇹🇷Istanbul, Turkey
Investigational Site Number : 7920005
🇹🇷Istanbul, Turkey
Investigational Site Number : 7920008
🇹🇷Istanbul, Turkey
Investigational Site Number : 7920001
🇹🇷Istanbul, Turkey
Investigational Site Number : 8260002
🇬🇧Leicester, Leicestershire, United Kingdom
Investigational Site Number : 8260005
🇬🇧London, London, City Of, United Kingdom
Investigational Site Number : 8260001
🇬🇧Norwich, Norfolk, United Kingdom
Investigational Site Number : 8260004
🇬🇧Birmingham, United Kingdom
Investigational Site Number : 8260003
🇬🇧Derby, United Kingdom