A Study of the Efficacy of ABT-199 in Subjects With Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia With the 17p Deletion

A Phase 2 Open-Label Study of the Efficacy of ABT-199 (GDC-0199) in Subjects With Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia Harboring the 17p Deletion

This was an open-label, multicenter, global study to determine the efficacy of ABT-199 (Venetoclax) monotherapy in participants with relapsed/refractory (R/R) or previously untreated chronic lymphocytic leukemia (CLL) harboring 17p deletion.

Study Overview

• Status: Completed
• Conditions: Chronic Lymphocytic Leukemia; 17p Deletion; Cancer of the Blood and Bone Marrow
• Intervention / Treatment: Drug: ABT-199 (Main Cohort); Drug: ABT-199 (Safety Expansion Cohort)

Detailed Description

This study was designed to enroll approximately 150 participants in 2 cohorts: a main cohort of approximately 100 participants, and a safety expansion (SE) cohort of approximately 50 participants. The primary objective of the main cohort was to evaluate the efficacy of ABT-199 monotherapy in participants with R/R CLL harboring the 17p deletion. The primary objective of the safety expansion cohort was to evaluate the safety of ABT-199 in approximately 50 participants with R/R CLL harboring 17p deletion treated per updated tumor lysis syndrome (TLS) prophylaxis and management measures.

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital /ID# 98836
  • Victoria
    • Coburg, Victoria, Australia, 3058
      • John Fawkner Private Hospital /ID# 98835
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Ctr /ID# 91795
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital /ID# 91794
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Duplicate_Jewish General Hospital /ID# 99476
• France
  • Paris, France, 75651
    • Hopital Pitie Salpetriere /ID# 98842
  • Rouen, France, 76038
    • Centre Henri Becquerel /ID# 98838
  • Auvergne-Rhone-Alpes
    • Pierre Benite CEDEX, Auvergne-Rhone-Alpes, France, 69495
      • Centre Hospitalier Lyon Sud /ID# 98839
  • Ile-de-France
    • Bobigny, Ile-de-France, France, 93000
      • Hopital Avicenne - APHP /ID# 98840
• Germany
  • Dresden, Germany, 01307
    • Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 113256
  • Freiburg, Germany, 79106
    • Universitaetsklinikum Freiburg /ID# 113276
  • Göttingen, Germany, 37075
    • Universitaetsmedizin Goettingen /ID# 113258
  • Mainz, Germany, 55131
    • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz /ID# 113236
  • Muenchen, Germany, 80804
    • Muenchen Klinik Schwabing /ID# 113275
  • Baden-Wuerttemberg
    • Heidelberg, Baden-Wuerttemberg, Germany, 69120
      • Universitaetsklinik Heidelberg /ID# 98845
  • Nordrhein-Westfalen
    • Köln, Nordrhein-Westfalen, Germany, 50937
      • Uniklinik Koeln /ID# 98847
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Universitaetsklinikum Schleswig-Holstein Campus Kiel /ID# 113235
  • Thueringen
    • Ulm, Thueringen, Germany, 89081
      • Universitaetsklinikum Ulm /ID# 92533
• Poland
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-081
      • Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie /ID# 98848
  • Malopolskie
    • Krakow, Malopolskie, Poland, 31-501
      • SP ZOZ Szpital Uniwersytecki w Krakowie /ID# 98849
  • Opolskie
    • Opole, Opolskie, Poland, 46-020
      • Szpital Wojewodzki w Opolu /ID# 102855
• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • The Royal Bournemouth Hospital /ID# 118975
  • Cambridge, United Kingdom, CB2 0SP
    • Addenbrookes Hospital /ID# 119977
  • Leeds, United Kingdom, LS9 7TF
    • St. James University Hospital /ID# 98863
  • Liverpool, United Kingdom, L7 8XP
    • Royal Liverpool and Broadgreen /ID# 98860
  • London, United Kingdom, EC1A 7BE
    • St Bartholomew's Hospital, Bar /ID# 98862
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust /ID# 119975
  • Manchester, United Kingdom, M20 4BX
    • The Christie Hospital /ID# 98864
  • Oxford, United Kingdom, OX3 7LE
    • Oxford Univ Hosp NHS Trust /ID# 119976
  • Plymouth, United Kingdom, PL6 8DH
    • Derriford Hospital /ID# 118335
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital /ID# 98861
  • England
    • Leicester, England, United Kingdom, LE1 5WW
      • Leicester Royal Infirmary /ID# 98865
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719-1478
      • University of Arizona Cancer Center - North Campus /ID# 96748
  • California
    • Duarte, California, United States, 91010
      • City of Hope /ID# 112875
    • La Jolla, California, United States, 92093
      • Moore UC San Diego Cancer Center /ID# 91793
    • Stanford, California, United States, 94305-2200
      • Stanford University School of Med /ID# 105117
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital /ID# 96954
  • Illinois
    • Chicago, Illinois, United States, 60611-2927
      • Northwestern University Feinberg School of Medicine /ID# 92499
    • Chicago, Illinois, United States, 60637-1443
      • The University of Chicago Medical Center /ID# 96960
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hosp /ID# 92497
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute /ID# 92494
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System /ID# 97795
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack Univ Med Ctr /ID# 92500
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey /ID# 92513
  • New York
    • New York, New York, United States, 10032-3725
      • Columbia Univ Medical Center /ID# 103835
    • New York, New York, United States, 10032-3725
      • Columbia Univ Medical Center /ID# 94716
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Main Campus /ID# 92495
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center /ID# 92521

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant must be greater than or equal to 18 years of age.

• Participant must have diagnosis of chronic lymphocytic leukemia (CLL) that meets published 2008 Modified IWCLL NCI-WG (International Workshop for Chronic Lymphocytic Leukemia National Cancer Institute-Working Group) Guidelines.

  • Participant has an indication for treatment according to the 2008 Modified IWCLL NCI WG Guidelines;
  • Participant has clinically measurable disease (lymphocytosis > 5 × 10^9/L and/or palpable and measurable nodes by physical exam and/or organomegaly assessed by physical exam);
  • Participant must be refractory or have relapsed after receiving at least one prior line of therapy (participants that have progressed after 1 cycle of treatment or have completed at least 2 cycles of treatment for a given line of therapy) or previously untreated CLL (previously untreated CLL participants must have received no prior chemotherapy or immunotherapy. Participants with a history of emergency, loco-regional radiotherapy (e.g., for relief of compressive signs or symptoms) are eligible. In addition, participants must meet the CLL diagnostic criteria above and must have > 5 × 10^9/L B-Lymphocytes in the peripheral blood.);
  • Participants must have 17p deletion, assessed by local laboratory (in bone marrow or peripheral blood) or assessed by central laboratory (peripheral blood).
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2.

• Participant must have adequate bone marrow function at Screening as follows:

  • Absolute Neutrophil Count (ANC) greater than or equal to 1000/µL, or
  • For subjects with an ANC less than 1000/µL at Screening and bone marrow heavily infiltrated with underlying disease (unless cytopenia is clearly due to marrow involvement of CLL), growth factor support may be administered after Screening and prior to the first dose of ABT-199 to achieve the ANC eligibility criteria (greater than or equal to 1000/µL);
  • Platelets greater than 30,000/mm^3 (without transfusion support within 14 days of Screening, without evidence of mucosal bleeding, without known history of bleeding episode within 3 months of Screening, and without history of bleeding disorder);
  • Hemoglobin greater than or equal to 8.0 g/dL.

• Participant must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening as follows:

  • Activated partial thromboplastin time (aPTT) and prothrombin time (PT) not to exceed 1.5 × the upper limit of normal;
  • Calculated creatinine clearance greater than 50 mL/min using 24-hour Creatinine Clearance or modified Cockcroft-Gault equation (using Ideal Body Mass [IBM] instead of Mass). For participants that have body mass index (BMI) of > 30 kg/m^2 or < 19 kg/m^2, 24-hour measured urine creatinine clearance is required;
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3.0 × the upper normal limit of institution's normal range; Bilirubin less than or equal to 1.5 × upper limit of normal. Participants with Gilbert's Syndrome may have a bilirubin greater 1.5 × upper limit of normal, per correspondence between the investigator and AbbVie medical monitor.
• For participants at high risk of tumor lysis syndrome a pre-approval by the AbbVie medical monitor is required prior to enrollment.

Exclusion Criteria:

• Participant has undergone an allogeneic stem cell transplant.
• Participant has developed Richter's transformation confirmed by biopsy.
• Participant has prolymphocytic leukemia.
• Participant has active and uncontrolled autoimmune cytopenias (for 2 weeks prior to Screening), including autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura despite low dose corticosteroids.
• Participant has previously received ABT-199.
• Participant has received a biologic agent for anti-neoplastic intent within 30 days prior to the first dose of study drug.

• Participant has received any of the following within 14 days or 5 half-lives as applicable prior to the first dose of study drug, or has not recovered to less than Common Toxicity Criteria (CTC) grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:

  • Any anti-cancer therapy including chemotherapy, or radiotherapy;
  • Investigational therapy, including targeted small molecule agents.
• Participant has known allergy to both xanthine oxidase inhibitors and rasburicase.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Main Cohort; Participants received ABT-199 tablets once daily (QD) orally for up to 79 months. The starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg.	Drug: ABT-199 (Main Cohort); Participants received a test dose of ABT-199 of ≤ 20 mg on Week 1 Day 1 of the Lead-In Period. For those with significant electrolyte and/or lymphocyte changes within 24 hours of the first dose, the 20 mg dose was maintained for 7 days with escalation to 50 mg on Week 2 Day 1. If none of the electrolyte and/or lymphocyte changes occurred within 24 hours from ABT-199 20 mg dose administration, the participant was dose-escalated to 50 mg on Week 1 Day 2. After the first dose of 50 mg, if no laboratory abnormalities occurred, the participant remained on the 50 mg dose through Week 1. After receiving the 50 mg dose for approximately 1 week (6 to 7 days), the following dose escalation proceeded with weekly increases in dose: → 100 mg → 200 mg → 400 mg (or additional lead-in steps to designated 400 mg dose), as tolerated.; Other Names: GDC-0199; Venetoclax
EXPERIMENTAL: Safety Expansion Cohort; Participants received ABT-199 tablets once daily (QD) orally for up to 68 months. The starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg.	Drug: ABT-199 (Safety Expansion Cohort); Participants received an initial dose of ABT-199 of 20 mg on Week 1 Day 1 of the Lead-In Period. If one or more electrolyte changes (from the 0 hr measurement prior to dosing) suggestive of laboratory tumor lysis syndrome (LTLS) or clinical TLS (CTLS) occurred within 24 hours of the 20 mg dose, no additional doses were administered until resolution. Upon resolution of laboratory abnormalities, the 20 mg dose was continued through Week 1. If no significant findings suggestive of clinical or laboratory TLS occurred within 24 hours, the 20 mg dose was continued through Week 1 Day 7, and escalated to a dose of 50 mg on Week 2 Day 1. Those who had drug interruptions may have been allowed to escalate to and be maintained at 50 mg for 1 week after they had been on a 20 mg dose for at least 1 week (5 - 7 days). After a week at 50 mg, weekly dose escalations were implemented as follows: 100 mg → 200 mg → 400 mg (or additional lead-in steps to designated 400 mg dose) as tolerated.; Other Names: GDC-0199; Venetoclax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (Main Cohort)	The overall response rate (ORR) is defined as the proportion of participants with an overall response (complete remission [CR] + complete remission with incomplete marrow recovery [CRi] + nodular partial remission [nPR] + partial remission [PR]) per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute-Working Group (NCI-CWG) criteria as assessed by the Independent Review Committee (IRC) in the first 70 participants treated in the Main Cohort.	Up to 36 weeks
Number of Participants With Adverse Events (Safety Expansion Cohort)	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.	From the first dose of study drug until 30 days following last dose of study drug (up to 69 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) (Safety Expansion Cohort)	The overall response rate (ORR) is defined as the proportion of participants with an overall response (complete remission [CR] + complete remission with incomplete marrow recovery [CRi] + nodular partial remission [nPR] + partial remission [PR]) per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute-Working Group (NCI-CWG) criteria.	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up
Complete Remission (CR) Rate	Complete remission was defined as the proportion of participants who achieved a CR or Complete Remission with Incomplete Marrow Recovery(CRi ) per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute-Working Group (NCI-CWG) criteria. Participants who did not achieve a CR or CRi were considered to be non-responders in the calculation of CR rate.	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up
Partial Remission (PR) Rate	PR rate was defined as the proportion of participants who achieved a nodular partial remission (nPR) or PR per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute-Working Group (NCI-CWG) criteria. Participants who did not achieve a nPR or PR were considered to be non-responders in the calculation of PR rate.	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up
Duration of Overall Response	Duration of overall response (DoR) was defined as the number of days from the date of first response (CR, CRi, nPR, or PR) by either CT scan or physical exam determination to the earliest recurrence (progressive disease; PD) or death. For participants who had a PR before CR, CRi, or nPR in subsequent visits, the DoR was computed from the earliest PR. If a participant was still responding, then their data was censored at the date of their last available disease assessment. To be included in the DoR analysis, participants must have had a response per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute-Working Group (NCI-CWG) criteria (CR, CRi, confirmed nPR, or confirmed PR). For participants who never experienced response, their data was not included in the analysis.	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up
Progression-free Survival	Duration of progression-free survival (PFS) was defined as the number of days from the date of first dose to the date of earliest disease progression or death. All disease progression was included regardless of whether the event occurred while the participant was taking ABT-199 or had previously discontinued ABT-199. If the participant does not experience disease progression or death, then the data was censored at the date of last disease assessment. Data for participants without any disease assessments performed after the baseline visit were censored at the date of first dose plus 1 day.	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up
Event-free Survival	Event-free survival (EFS) was defined as the number of days from the date of first dose to the date of earliest disease progression, death, or start of a new anti-leukemic therapy. If the specified event (disease progression, death, start of a new anti-leukemic treatment) did not occur, participants were censored at the date of last disease assessment. Data for participants without any disease assessments performed after the baseline visit were censored at the date of first dose plus 1 day.	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up
Time to Progression	Time to progression (TTP) was defined as the number of days from the date of first dose to the date of earliest disease progression. All disease progression was included regardless of whether the event occurred while the participant was taking ABT-199 or had previously discontinued ABT-199. If the participant did not experience disease progression, then the data was censored at the date of last available disease assessment. Data for participants without any disease assessments performed after the baseline visit were censored at the date of first dose plus 1 day.	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up
Time to First Response	Time to first response was defined as the number of days from the date of first dose to the date of the first sign of response (CR, CRi, nPR, or PR) given the participant has had a CR, CRi, confirmed nPR, or confirmed PR per the 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute-Working Group (NCI-CWG) criteria. The first response could have been an assessment by physical exam as long as the results were later confirmed per the 2008 Modified IWCLL NCI-WG criteria. For participants who never experienced a response, the participant's data were not included in the analysis.	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up
Time to 50% Reduction in Absolute Lymphocyte Count	Time to 50% reduction in absolute lymphocyte count (ALC) was defined as the number of days (hours if applicable) from the date of first dose to the date when the ALC had reduced to 50% of the baseline value. Only participants with a baseline of ALC > 5 × 10^9 /L were included in the analysis. For participants who never achieved a 50% reduction in ALC, the participant's data were not included in the analysis.	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up
Overall Survival	Overall survival (OS) was defined as number of days from the date of first dose to the date of death. For participants who did not die, their data was censored at the date of last study visit or the last known date to be alive, whichever was later.	Up to the data cutoff date of 15 December 2020, approximately 7.5 years of follow-up
Percentage of Participants Who Moved on to Stem Cell Transplant	The percentage of participants who moved on to stem cell transplant was summarized.	Up to the data cutoff date of 15 June 2017, approximately 4 years of follow-up

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: Genentech, Inc.

Publications and helpful links

General Publications

• Stilgenbauer S, Eichhorst B, Schetelig J, Coutre S, Seymour JF, Munir T, Puvvada SD, Wendtner CM, Roberts AW, Jurczak W, Mulligan SP, Bottcher S, Mobasher M, Zhu M, Desai M, Chyla B, Verdugo M, Enschede SH, Cerri E, Humerickhouse R, Gordon G, Hallek M, Wierda WG. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. Lancet Oncol. 2016 Jun;17(6):768-778. doi: 10.1016/S1470-2045(16)30019-5. Epub 2016 May 10.
• Roberts AW, Ma S, Kipps TJ, Coutre SE, Davids MS, Eichhorst B, Hallek M, Byrd JC, Humphrey K, Zhou L, Chyla B, Nielsen J, Potluri J, Kim SY, Verdugo M, Stilgenbauer S, Wierda WG, Seymour JF. Efficacy of venetoclax in relapsed chronic lymphocytic leukemia is influenced by disease and response variables. Blood. 2019 Jul 11;134(2):111-122. doi: 10.1182/blood.2018882555. Epub 2019 Apr 25.
• Stilgenbauer S, Eichhorst B, Schetelig J, Hillmen P, Seymour JF, Coutre S, Jurczak W, Mulligan SP, Schuh A, Assouline S, Wendtner CM, Roberts AW, Davids MS, Bloehdorn J, Munir T, Bottcher S, Zhou L, Salem AH, Desai M, Chyla B, Arzt J, Kim SY, Verdugo M, Gordon G, Hallek M, Wierda WG. Venetoclax for Patients With Chronic Lymphocytic Leukemia With 17p Deletion: Results From the Full Population of a Phase II Pivotal Trial. J Clin Oncol. 2018 Jul 1;36(19):1973-1980. doi: 10.1200/JCO.2017.76.6840. Epub 2018 May 1. Erratum In: J Clin Oncol. 2019 Sep 1;37(25):2299.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 27, 2013
• Primary Completion (ACTUAL): October 28, 2020
• Study Completion (ACTUAL): December 15, 2020

Study Registration Dates

• First Submitted: June 26, 2013
• First Submitted That Met QC Criteria: June 27, 2013
• First Posted (ESTIMATE): June 28, 2013

Study Record Updates

• Last Update Posted (ACTUAL): December 16, 2021
• Last Update Submitted That Met QC Criteria: November 19, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Chronic Lymphocytic Leukemia; 17p Deletion
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Antineoplastic Agents; Venetoclax
• Other Study ID Numbers: M13-982; 2012-004027-20 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• 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