- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03527147
Platform Study for the Treatment of Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma (PRISM Study) (PRISM)
PRISM: A Platform Protocol for the Treatment of Relapsed/Refractory Aggressive Non-Hodgkin's Lymphoma
Study Overview
Status
Intervention / Treatment
Detailed Description
This is a Phase 1 platform protocol designed to evaluate various targeted agents for the treatment of relapsed/refractory aggressive Non-Hodgkin's lymphoma (NHL). Each study arm will be conducted in a predefined disease subset. All study arms are open label and allocation to each study arm will not be randomized.
As this master platform protocol has multiple study arms, subjects can be screened for several study arms at once. Likewise, a subject who ends participation in one study arm may be rescreened for participation in another (separate) study arm.
The primary objective of the study is to evaluate the safety of targeted agents for the treatment of relapsed/refractory aggressive Non-Hodgkin's Lymphoma (NHL). This protocol has a modular design, with the potential for future treatment arms to be added via protocol amendment.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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London, United Kingdom, W1G 6AD
- Research Site
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Oxford, United Kingdom, OX3 7EJ
- Research Site
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California
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Los Angeles, California, United States, 90095
- Research Site
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Florida
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Sarasota, Florida, United States, 34232
- Research Site
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Georgia
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Atlanta, Georgia, United States, 30322
- Research Site
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Louisiana
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New Orleans, Louisiana, United States, 70112
- Research Site
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Maryland
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Bethesda, Maryland, United States, 20892
- Research Site
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Nebraska
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Omaha, Nebraska, United States, 68198
- Research Site
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New York
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Rochester, New York, United States, 14642
- Research Site
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Tennessee
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Nashville, Tennessee, United States, 37203
- Research Site
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Virginia
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Charlottesville, Virginia, United States, 22908
- Research Site
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Washington
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Seattle, Washington, United States, 98104
- Research Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Inclusion Criteria For All Arms:
- Diagnosis of relapsed/refractory aggressive Non Hodgkin's Lymphoma (NHL) with histology based on established World Health Organization (WHO) criteria.
- Must have received ≥1 prior line of therapy for the treatment of current histology, there are no known curative treatment options available, or subject ineligible for potential curative options.
- Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy. Not applicable for cutaneous lesions.
- ECOG performance status of ≤2.
Inclusion Criteria for Arm 1:
1. Must have previously received rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate, and prednisone or equivalent regimen with stem-cell rescue. Or who are ineligible for highdose chemotherapy with stem-cell rescue and/or chimeric antigen receptor (CAR) T cell therapy.
Ineligibility for high-dose therapy with stem cell rescue and/or CAR T-cell therapy will be determined by the investigator.
Inclusion Criteria for Arm 2:
1. Must have previously received rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate, and prednisone or equivalent regimen with stem-cell rescue. Or who are ineligible for highdose chemotherapy with stem-cell rescue and/or chimeric antigen receptor (CAR) T-cell therapy.
Ineligibility for high-dose therapy with stem cell rescue and/or CAR T-cell therapy will be determined by the investigator.
Inclusion Criteria for Arm 3:
1. Must have previously received rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate, and prednisone or equivalent regimen with stem-cell rescue. Or who are ineligible for highdose chemotherapy with stem-cell rescue and/or chimeric antigen receptor (CAR) T cell therapy.
Ineligibility for high-dose therapy with stem cell rescue and/or CAR T-cell therapy will be determined by the investigator.
Inclusion Criteria for Arm 4:
1. Must have previously received rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate, and prednisone or equivalent regimen with stem-cell rescue. Or who are ineligible for highdose chemotherapy with stem-cell rescue and/or chimeric antigen receptor (CAR) T cell therapy.
Ineligibility for high-dose therapy with stem cell rescue and/or CAR T-cell therapy will be determined by the investigator.
Exclusion Criteria:
Exclusion Criteria For All Arms:
- History of prior malignancy except for the following: a) Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening and felt to be at low risk for recurrence by treating physician, b) Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled nonmelanomatous skin cancer, c) Adequately treated carcinoma in situ without current evidence of disease, d) Evidence of severe or uncontrolled systemic disease, or current unstable or uncompensated respiratory or cardiac conditions, or uncontrolled hypertension, history of, or active, bleeding diatheses or uncontrolled active systemic fungal, bacterial, viral, or other infection, or intravenous anti-infective treatment within 2 weeks before first dose of study treatment.
- Serologic status reflecting active hepatitis B or C infection.
- Prior use of standard antilymphoma therapy or radiation therapy within 14 days of receiving the first dose of study treatment (not including palliative radiotherapy or palliative corticosteroid use).
- Requires ongoing immunosuppressive therapy, including systemic corticosteroids for treatment of lymphoid cancer or other conditions.
- For subjects under DLT review only: Any haematopoietic growth factors or darbepoetin within 14 days of the first dose of study treatment.
Exclusion Criteria for Arm 1:
- Presence of central nervous system (CNS) lymphoma or leptomeningeal disease.
- Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal (GI) function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
- Requires treatment with proton-pump inhibitors.
- Requires treatment with strong CYP3A inhibitors or inducers.
Exclusion Criteria for Arm 2:
- Relative hypotension (< 90/60 mm Hg) or clinically relevant orthostatic hypotension, including a fall in blood pressure of >20 mm Hg.
- Uncontrolled hypertension requiring clinical intervention.
- At risk for brain perfusion problems based on medical history.
- Mean resting QT interval (QTc) calculated using Fridericia's formula (QTcF) >470 msec for female subjects and >450 msec for male subjects obtained from 3 electrocardiograms (ECGs), or congenital long QT syndrome.
- Presence of central nervous system (CNS) lymphoma or leptomeningeal disease.
- Known to have tested positive for human immunodeficiency virus (HIV) & requires treatment with restricted medications.
- Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal (GI) function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
- Requires treatment with proton-pump inhibitors.
Exclusion Criteria for Arm 3:
- Presence of central nervous system (CNS) lymphoma or leptomeningeal disease.
- Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal (GI) function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
- Requires treatment with proton-pump inhibitors.
- Red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of RBC transfusions during the 4-week period prior to screening.
- History of haemolytic anaemia or Evans syndrome in the last 3 months before enrolment.
- Positive IgG component of the direct antiglobulin test (DAT).
- Prior treatment with CD47 or SIRPα-targeting agents.
- Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients of rituximab
Exclusion Criteria for Arm 4:
- Presence of central nervous system (CNS) lymphoma or leptomeningeal disease.
- Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal (GI) function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
- Requires treatment with proton-pump inhibitors.
- Requires treatment with CYP3A inhibitors or inducers or substrates of drug transporters.
- History of tuberculosis.
- Mean resting corrected QT interval (QTcF) >450 msec obtained from 3 electrocardiograms (ECGs); clinically important ECG findings, or risk factors for QTc prolongation.
- Subjects receiving antiplatelet or anticoagulant therapies within 28 days of first dose of study drug.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: AZD9150 + Acalabrutinib
AZD9150 given in combination with acalabrutinib
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AZD9150 will be administered as a 1-hour intravenous (IV) infusion on Days 1, 3, 5 of Cycle 1, followed by weekly infusions (starting Day 8 of Cycle 1 and beyond).
Other Names:
Acalabrutinib will be administered orally twice daily (bid).
Other Names:
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EXPERIMENTAL: AZD6738 + Acalabrutinib
AZD6738 in combination with acalabrutinib
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Acalabrutinib will be administered orally twice daily (bid).
Other Names:
AZD6738 will be administered orally twice daily (bid).
Other Names:
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EXPERIMENTAL: Hu5F9-G4 + rituximab + Acalabrutinib
Hu5F9-G4/rituximab in combination with acalabrutinib
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Acalabrutinib will be administered orally twice daily (bid).
Other Names:
HU5F9-G4 infusions will be given on Weekly (Day 1, 8, 15, and 22) during the first two 28-day cycles, then will be given every two weeks (Day 1 and Day 15) in Cycle 3 and beyond.
Other Names:
Rituximab infusions will be given Weekly starting on Day 8 (Day 8, 15, and 22) during the first 28-day cycle (4 weeks), then Day 1 of each 4 week cycle for Cycles 2-6.
Starting with Cycle 8, Rituximab will be infused on Day 1 of every other cycle (every 8 weeks).
Other Names:
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EXPERIMENTAL: AZD5153 + Acalabrutinib
AZD5153 in combination with acalabrutinib
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Acalabrutinib will be administered orally twice daily (bid).
Other Names:
AZD5153 will be administered orally once per day (qd).
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Safety of the study treatments when given in combination [Incidence of adverse events]
Time Frame: Through to study completion, an average of 1 year
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Incidence of adverse events
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Through to study completion, an average of 1 year
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Assessment of the efficacy of each treatment by evaluation of overall response rate using RECIL 2017 response criteria
Time Frame: Through to study completion, an average of 1 year
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The overall response rate (ORR) is defined as the rate of subjects who achieve either a partial response (PR) or complete response (CR) as assessed by investigators before receiving any other anticancer therapy.
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Through to study completion, an average of 1 year
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Duration of response (DOR) using RECIL 2017 response criteria for the anti-tumour activity of each therapy.
Time Frame: Through to study completion, an average of 1 year
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Duration of Response (DOR) is defined as the time from the first objective response of CR or PR to the time of documented disease progression or death due to any cause, whichever occurs first.
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Through to study completion, an average of 1 year
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Progression free survival (PFS) using RECIL 2017 response criteria for the anti-tumour activity of each therapy.
Time Frame: Through to study completion, an average of 1 year
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Progression free survival (PFS) is defined as the time from first dose date to documented objective disease progression, or death from any cause, whichever occurs first.
Disease progression will be determined by the investigators per standard response criteria as outlined in each respective study arm.
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Through to study completion, an average of 1 year
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Overall Survival (OS)
Time Frame: From the beginning of treatment until the date of death from any cause, assessed up to 12 months
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Overall Survival (OS) is defined as the time from first dose until the date of death from any cause.
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From the beginning of treatment until the date of death from any cause, assessed up to 12 months
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Peak plasma concentration (Cmax) of Study Drug A (Arm 1)
Time Frame: Samples will be collected predose and 1, 4, 6 hours postdose on Cycle 1 Day 8 only; then predose and approximately 1 hr (end of infusion of Study Drug A) on Day 1 of every odd cycle starting with Cycle 3 through study completion, an average of 1 year
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Samples will be collected predose and 1, 4, 6 hours postdose on Cycle 1 Day 8 only; then predose and approximately 1 hr (end of infusion of Study Drug A) on Day 1 of every odd cycle starting with Cycle 3 through study completion, an average of 1 year
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Peak plasma concentration (Cmax) of Study Drug B (Arm 2)
Time Frame: Samples will be collected predose and 1, 4, 8 hours postdose on Cycle 1 Day 8 only; then predose on Cycle 2 Day 1 and Cycle 3 Day 1
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Samples will be collected predose and 1, 4, 8 hours postdose on Cycle 1 Day 8 only; then predose on Cycle 2 Day 1 and Cycle 3 Day 1
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Area under the plasma concentration versus time curve (AUC) of Study Drug A (Arm 1)
Time Frame: Samples will be collected predose and 1, 4, 6 hours postdose on Cycle 1 Day 8 only; then predose and approximately 1 hr (end of infusion of Study Drug A) on Day 1 of every odd cycle starting with Cycle 3 through study completion, an average of 1 year
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Samples will be collected predose and 1, 4, 6 hours postdose on Cycle 1 Day 8 only; then predose and approximately 1 hr (end of infusion of Study Drug A) on Day 1 of every odd cycle starting with Cycle 3 through study completion, an average of 1 year
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Area under the plasma concentration versus time curve (AUC) of Study Drug B (Arm 2)
Time Frame: Samples will be collected predose and 1, 4, 8 hours postdose on Cycle 1 Day 8 only; then predose on Cycle 2 Day 1 and Cycle 3 Day 1
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Samples will be collected predose and 1, 4, 8 hours postdose on Cycle 1 Day 8 only; then predose on Cycle 2 Day 1 and Cycle 3 Day 1
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Presence of Anti-Drug Antibody (ADA) titres in subjects treated with Study Drug A
Time Frame: Samples will be collected predose on Days 1 and 8 of Cycle 1 and predose on Day 1 of every odd cycle starting with Cycle 3
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Samples will be collected predose on Days 1 and 8 of Cycle 1 and predose on Day 1 of every odd cycle starting with Cycle 3
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Peak plasma concentration (Cmax) of acalabrutinib (Arm 1)
Time Frame: Samples will be collected predose and 1, 4, 6 hours postdose on Cycle 1 Day 8 only
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Samples will be collected predose and 1, 4, 6 hours postdose on Cycle 1 Day 8 only
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Area under the plasma concentration versus time curve (AUC) for acalabrutinib (Arm 1)
Time Frame: Samples will be collected predose and 1, 4, 6 hours postdose on Cycle 1 Day 8 only
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Samples will be collected predose and 1, 4, 6 hours postdose on Cycle 1 Day 8 only
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Peak plasma concentration (Cmax) of acalabrutinib (Arm 2)
Time Frame: Samples will be collected predose and 1, 4, 8 hours postdose on Cycle 1 Day 8 only; then predose on Cycle 2 Day 1 and Cycle 3 Day 1
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Samples will be collected predose and 1, 4, 8 hours postdose on Cycle 1 Day 8 only; then predose on Cycle 2 Day 1 and Cycle 3 Day 1
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Area under the plasma concentration versus time curve (AUC) for acalabrutinib (Arm 2)
Time Frame: Samples will be collected predose and 1, 4, 8 hours postdose on Cycle 1 Day 8 only; then predose on Cycle 2 Day 1 and Cycle 3 Day 1
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Samples will be collected predose and 1, 4, 8 hours postdose on Cycle 1 Day 8 only; then predose on Cycle 2 Day 1 and Cycle 3 Day 1
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Ian Flinn, MD, PhD, Tennessee Oncology
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, B-Cell
- Lymphoma
- Lymphoma, Large B-Cell, Diffuse
- Lymphoma, Non-Hodgkin
- Physiological Effects of Drugs
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Rituximab
- Acalabrutinib
- Magrolimab
Other Study ID Numbers
- ACE-LY-111
- 2017-004191-63 (EUDRACT_NUMBER)
- D9820C00001 (OTHER: AstraZeneca)
- LYM 138 (OTHER: Sarah Cannon Development Innovations)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
IPD Sharing Time Frame
IPD Sharing Access Criteria
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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