A Study of Imatinib Versus Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) (ENESTnd)

• ClinicalTrials.gov Identifier: NCT00471497
• Recruitment Status: Completed
• First Posted: May 10, 2007
• Results First Posted: June 17, 2013
• Last Update Posted: November 18, 2020
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: May 7, 2007
• First Posted Date: May 10, 2007
• Results First Submitted Date: April 10, 2013
• Results First Posted Date: June 17, 2013
• Last Update Posted Date: November 18, 2020
• Actual Study Start Date: July 31, 2007
• Actual Primary Completion Date: September 2, 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 23, 2020)

• Major Molecular Response Rate (MMR) at 12 Months Between All 3 Arms - With Imputation [ Time Frame: Baseline, 12 months ]
  MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 12 months.
• Percentage of Participants With MMR at 12 Months Between All 3 Arms by Sokal Risk Group With Imputation [ Time Frame: 12 months ]
  MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 12 months.

• Original Primary Outcome Measures (submitted: May 9, 2007): Rate of major molecular response after 12 months of treatment assessed by the degree of elimination of the cells that carry the Bcr-Abl protein in the bone marrow.

Current Secondary Outcome Measures (submitted: October 23, 2020)

• Rates of Durable MMR at 24 Months Between All 3 Arms [ Time Frame: 24 months ]
  Durable MMR at 24 months is defined as having MMR both at 12 months and at 24 months, and with no documented loss of MMR between these 12 month and 24 month time points.
• Rate of Complete Cytogenetic Response (CCyR) in Nilotinib Treatment Arms With Imatinib at 12 Months and Beyond 12 Months [ Time Frame: 12, 24, 36, 48, 60, 72 months (M) ]
  CCyR is defined as 0% Ph+ metaphases based on at least 20 metaphases from bone marrow cytogenetics. Patients with no CCyR as the best response by any specific time point, all missing cytogenetic evaluations by that time point or Ph- at baseline are combined as "Nocomplete cytogenetic response".
• Rate of Major Molecular Response (MMR) at 12 Months Between Two Nilotinib Arms [ Time Frame: 12 months ]
  MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 12 months based on 12-month cut-off interim data.
• Rate of MMR at 6 Months and Beyond in All 3 Treatment Arms [ Time Frame: 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months ]
  MMR is defined as the percentage of participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR)) at 6 months and beyond up to 120 months based on final data.
• Rate of a ≥ 4 Log Reduction in BCR-ABL Transcripts in Nilotinib Treatment Arms With Imatinib [ Time Frame: at 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months ]
  Molecular response of <=0.01% is defined as BCR-ABL ratio (%) on IS <= 0.01% (corresponds to >=4 log reduction of BCR-ABL transcripts from standardized baseline value)
• Rate of a ≥ 4.5 Log Reduction in BCR-ABL Transcripts in Nilotinib Treatment Arms With Imatinib [ Time Frame: at 6, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 months ]
  This is the molecular response of <=0.0032% is defined as BCR-ABL ratio (%) on IS <= 0.0032% (corresponds to >=4.5 log reduction of BCR-ABL transcripts from standardized baseline value)
• Time to First MMR [ Time Frame: up to 84 months ]
  Time to MMR is defined as time from date of randomization to the date of the first documented MMR in nilotinib treatment arms, compared to imatinib in adult patients with Ph+ CML in CP.
• Duration of MMR [ Time Frame: approx. 11 years ]
  Duration of MMR for patients with MMR is defined as the time between date of MMR and the earliest of the following: loss of MMR, CML-related death or progression to AP/BC during study treatment The time will be censored at last molecular assessment (PCR) date for patients for whom none of the above events is reported.
• Time to Both a ≥ 4 and ≥ 4.5 Log Reduction in BCR-ABL Transcripts [ Time Frame: up to 84 months ]
  Time to BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032% is defined as: date of first BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032% - date of randomization +1.
• Duration of Both a ≥ 4 and ≥ 4.5 Log Reduction in BCR-ABL Transcripts [ Time Frame: approx. 11 years ]
  It is defined as the time from the date of first documented BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032% to the earliest of the following: Loss of BCR-ABL ratio of ≤ 0.01% and ≤ 0.0032%, respectively, CML-related death or progression to AP/BC during study treatment. The time will be censored at last molecular assessment (PCR) date for patients for whom none of the above events is reported.
• Rate of Hematologic Response [ Time Frame: 12 months, 24 months, Overall on Core study (approx. 11 years) ]
  Rate of hematologic response is defined as the percentage of participants in complete hematologic response (defined as the following present for at least 4 weeks: WBC count <10 x 109/L, Platelet count <450 x 109/L, Basophils <5%, No blasts and promyelocytes in peripheral blood, Myelocytes + metamyelocytes < 5% in peripheral blood, No evidence of extramedullary disease, including spleen and liver).
• Time to Complete Cytogenic Response (CCyR) [ Time Frame: 24 months ]
  Time to CCyR is defined as the time from the date of randomization to the date of first documented CCyR
• Duration of CCyR [ Time Frame: up to 72 months ]
  Duration of CCyR is defined as the time from date of first documented CCyR to the earliest date of loss of CCyR.
• Progression-free Survival (PFS) [ Time Frame: approx. 11 years ]
  Progression-free survival is defined as the time from the date of randomization to the date of event defined as the first documented disease progression to AP/BC or the date of death from any cause occurring in the core or extension study, or during the follow-up period after discontinuation of core or extension study
• Event-free Survival (EFS) [ Time Frame: approx. 11 years ]
  Event-free survival is defined as the time from the date of randomization to the date of first occurrence of any of the following: death due to any cause (if death is the primary reason for discontinuation), progression to AP or BC, loss of PCyR, loss of CCyR, loss of CHR
• Overall Survival (OS) [ Time Frame: approx. 11 years ]
  OS is defined as the time from the date of randomization to the date death. Up to 10 calendar years of follow up from the date when the last patient randomized received the first dose of study drug in all active treatment arms of adult patients with Ph+ CML CP.
• Actual Dose-intensity [ Time Frame: approx. 11 years ]
  Actual dose intensity is defined as total dose over time on treatment
• Time to Progression to AP/BC [ Time Frame: approx. 11 years ]
  Time to progression to AP/BC is defined as the time from the date of randomization to the date of event defined as the first documented disease progression to AP/BC or the date of CML related death.
• Pharmacokinetics: Cmax [ Time Frame: any day after day 8 up to cycle 12 (each cycle = 28 days) and after at least 3 consecutive days without dose interruption or dose modification at pre-dose (0 hour), 1 hour, 2 hours, 3 hours, 5 hours, 8 hours, and 12 hours after dose administration ]
  Cmax is defined as the maximum serum concentration after dose
• Pharmacokinetics: Cmin [ Time Frame: any day after day 8 up to cycle 12 (each cycle = 28 days) and after at least 3 consecutive days without dose interruption or dose modification at pre-dose (0 hour), 1 hour, 2 hours, 3 hours, 5 hours, 8 hours, and 12 hours after dose administration ]
  Cmin is defined as the minimum serum concentration after dose
• Pharmacokinetics: Tmax [ Time Frame: any day after day 8 up to cycle 12 (each cycle = 28 days) and after at least 3 consecutive days without dose interruption or dose modification at pre-dose (0 hour), 1 hour, 2 hours, 3 hours, 5 hours, 8 hours, and 12 hours after dose administration ]
  Tmax is defined as the sampling time when maximum measured serum concentration occurs
• Pharmacokinetics: AUC0-last [ Time Frame: any day after day 8 up to cycle 12 (each cycle = 28 days) and after at least 3 consecutive days without dose interruption or dose modification at pre-dose (0 hour), 1 hour, 2 hours, 3 hours, 5 hours, 8 hours, and 12 hours after dose administration ]
  AUC0-last is defined as area under concentration-time curve from time zero to the last measurable sample, calculated by log-linear trapezoidal method
• Rate of Hematologic Response on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension) [ Time Frame: Overall for Extension study for approx. 10 years ]
  Rate of hematologic response is defined as the percentage of participants in complete hematologic response (defined as the following present for at least 4 weeks: WBC count <10 x 109/L, Platelet count <450 x 109/L, Basophils <5%, No blasts and promyelocytes in peripheral blood, Myelocytes + metamyelocytes < 5% in peripheral blood, No evidence of extramedullary disease, including spleen and liver).
• Rate of Complete Cytogenetic Response (CCyR) on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension) [ Time Frame: Overall for Extension study for approx. 10 years ]
  Rate of CCyR is defined as the percentage of participants in complete cytogenetic response (CCyR). CcyR is defined as 0% of Ph+ metaphases in the bone marrow.
• Rate of Major Molecular Response (MMR) on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension) [ Time Frame: Overall for Extension study for approx. 10 years ]
  Rate of MMR is defined as the percentage pf participants in MMR (reduction of ≥ 3 logs in BCR-ABL transcripts compared to the standardized baseline established in IRIS, or ≤ 0.1% BCR-ABL/ABL % by international scale and measured by real-time quantitative polymerase chain reaction (RQ-PCR))
• Rate of a ≥ 4 Log Reduction in BCR-ABL Transcripts on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension) [ Time Frame: Overall for Extension study for approx. 10 years ]
  Molecular response of <=0.01% is defined as BCR-ABL ratio (%) on IS <= 0.01% (corresponds to >=4 log reduction of BCR-ABL transcripts from standardized baseline value)
• Rate of ≥ 4.5 Log Reduction in BCR-ABL Transcripts on Nilotinib 400 mg BID Therapy After Insufficient Response During Core Treatment and Switch to Extension Phase (Extension) [ Time Frame: Overall for Extension study for approx. 10 years ]
  Molecular response of <=0.0032% is defined as BCR-ABL ratio (%) on IS <= 0.0032% (corresponds to >=4.5 log reduction of BCR-ABL transcripts from standardized baseline value)
• Presence of Newly Observed BCR-ABL Mutations in Patients Post-baseline and Correlate With Response to Treatment With Imatinib and Nilotinib (Extension) [ Time Frame: Overall for Extension study for approx. 10 years ]
  This is the percentage of patients with any emergent mutation on extension treatment. The mutation comprised of T315T, less sensitive to nilotinib, unknown and sensitive to nilotinib.

Original Secondary Outcome Measures (submitted: May 9, 2007)

• To compare the rate reduction in BCR-ABL transcript levels in nilotinib treatment arms with imatinib at 12 months.
• To compare the rate of complete cytogenetic response (CCyR) in nilotinib treatment arms with imatinib at 12 months.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Imatinib Versus Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
• Official Title: A Phase III Multi-center, Open-label, Randomized Study of Imatinib Versus Nilotinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)

Brief Summary

In this study, the efficacy and safety of two nilotinib doses, 300 mg twice daily and 400 mg twice daily, were compared with imatinib 400 mg once daily in newly diagnosed patients with Philadelphia chromosome-positive (Ph+) Chronic Myelogenous Leukemia in the chronic phase (CML-CP).

An extension protocol was included in this study design to allow patients who did not show sufficient response to their assigned treatments the opportunity to receive imatinib 400 mg BID (option available until protocol amendment 7) or nilotinib 400 mg BID, using an abbreviated safety and efficacy assessment schedule.

Detailed Description

Primary objectives of this study:

• Compared the efficacy (major molecular response (MMR) rate at 12 months) of nilotinib at 400 mg bid with that of imatinib 400 mg qd in newly diagnosed, previously untreated Ph+ CML-CP patients.
• Compared the efficacy (MMR rate at 12 months) of nilotinib at 300 mg bid with that of imatinib 400 mg qd in newly diagnosed, previously untreated Ph+ CML-CP patients.

The Primary objectives of Extension Phase of the study:

- Characterized the safety and tolerability profile of nilotinib 400 mg BID after failure of imatinib or insufficiently responded to nilotinib 300 mg BID therapy and the safety and tolerability profile of imatinib therapy after failure of nilotinib therapy.

The study was designed to determine whether the treatment of newly diagnosed, previously untreated Ph+ CML-CP patients with either nilotinib 300 mg bid or 400 mg bid demonstrated improved efficacy compared to imatinib 400 mg qd. The primary efficacy endpoint was the rate of MMR defined as the proportion of patients who achieved ≥ 3 log reduction in BCR-ABL transcripts compared to either the standardized Baseline established in the IRIS trial (International Randomized Interferon versus STI571) (Cortes et al 2005) or to the BCR-ABL ratio ≤ 0.1% by International Scale, as detected by real-time quantitative polymerase chain reaction (RQ-PCR) at 12 months.

The key secondary endpoint was to compare the rate of durable MMR between nilotinib 300 mg bid with that of imatinib, and of nilotinib 400 mg bid with that of imatinib at 24 months. This report presents the final results of efficacy and safety at the LPLV (21-Aug-2019).

The main data analysis was done at the time when all patients completed 12 cycles of treatment (or discontinued earlier). There were two primary comparisons at this time point: the MMR rate of nilotinib 400 mg versus the MMR rate of imatinib 400 mg, and the MMR rate of the nilotinib 300 mg versus the MMR rate of the imatinib 400 mg. Comparisons were done sequentially, i.e. the MMR rate of nilotinib 400 mg versus the MMR rate of imatinib 400 mg was to be compared first; if it was significant at 5% level, the MMR rate of the nilotinib 300 mg versus the MMR rate of the imatinib 400 mg was to be compared. The study had a 90% power to detect a 15% difference between the nilotinib 400 mg arm versus imatinib 400 mg arm assuming that the MMR rate of imatinib is 40% and the MMR rate of nilotinib is 55%. The study also had a 90% power to detect a 15% difference between the nilotinib 300 mg and the imatinib 400 mg arms, if the comparison between the nilotinib 400 mg and the imatinib 400 mg was significant.

The second main data analysis was done at the time when all patients completed 24 cycles of treatment (or discontinued earlier). There were two key comparisons at this time point: the rate of durable MMR at 24 months of the nilotinib 400 mg versus the imatinib 400 mg, and the rate of durable MMR at 24 months of the nilotinib 300 mg versus the imatinib 400 mg.

In order to control the overall type I error rate at or below 5%, only when the corresponding comparison on the primary efficacy endpoint(s) was (were) significant, the key secondary comparison(s) of the respective nilotinib doses (400 mg bid and/or 300 mg bid) versus imatinib 400 mg qd were tested at two-sided 5% significance level.

Patients participating after demonstrating suboptimal response/treatment failure to their assigned study treatment in the core study were offered the option to continue in the extension study and to receive imatinib 400 mg bid (option available only until protocol amendment 7) or nilotinib therapy at a dose of 400 mg bid.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Myelogenous Leukemia, Chronic

Intervention

• Drug: nilotinib
  Nilotinib was supplied as 50 mg, 150 mg and 200 mg hard gelatin capsules and administered orally at 300 mg BID (twice a day) or 400 mg BID (twice a day)depending on the randomized dose.
  Other Name: AMN107
• Drug: imatinib
  Imatinib was supplied as 100 mg and 400 mg tablets and administered orally at 400 mg QD (once a day).
  Other Name: STI571

Study Arms

• Experimental: nilotinib 300mg bid (investigating arm)
  Intervention: Drug: nilotinib
• Experimental: Nilotinb 400 mg bid (investigating arm)
  Intervention: Drug: nilotinib
• Experimental: imatinib 400mg QD (control arm)
  Intervention: Drug: imatinib

Publications *

• Hughes TP, Hochhaus A, Kantarjian HM, Cervantes F, Guilhot F, Niederwieser D, le Coutre PD, Rosti G, Ossenkoppele G, Lobo C, Shibayama H, Fan X, Menssen HD, Kemp C, Larson RA, Saglio G. Safety and efficacy of switching to nilotinib 400 mg twice daily for patients with chronic myeloid leukemia in chronic phase with suboptimal response or failure on front-line imatinib or nilotinib 300 mg twice daily. Haematologica. 2014 Jul;99(7):1204-11. doi: 10.3324/haematol.2013.091272. Epub 2014 Feb 14.
• Hughes TP, Saglio G, Kantarjian HM, Guilhot F, Niederwieser D, Rosti G, Nakaseko C, De Souza CA, Kalaycio ME, Meier S, Fan X, Menssen HD, Larson RA, Hochhaus A. Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib. Blood. 2014 Feb 27;123(9):1353-60. doi: 10.1182/blood-2013-06-510396. Epub 2013 Dec 11.
• Hochhaus A, Saglio G, Larson RA, Kim DW, Etienne G, Rosti G, De Souza C, Kurokawa M, Kalaycio ME, Hoenekopp A, Fan X, Shou Y, Kantarjian HM, Hughes TP. Nilotinib is associated with a reduced incidence of BCR-ABL mutations vs imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Blood. 2013 May 2;121(18):3703-8. doi: 10.1182/blood-2012-04-423418. Epub 2013 Mar 15.
• Branford S, Kim DW, Soverini S, Haque A, Shou Y, Woodman RC, Kantarjian HM, Martinelli G, Radich JP, Saglio G, Hochhaus A, Hughes TP, Muller MC. Initial molecular response at 3 months may predict both response and event-free survival at 24 months in imatinib-resistant or -intolerant patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase treated with nilotinib. J Clin Oncol. 2012 Dec 10;30(35):4323-9. doi: 10.1200/JCO.2011.40.5217. Epub 2012 Oct 29.
• Larson RA, Yin OQ, Hochhaus A, Saglio G, Clark RE, Nakamae H, Gallagher NJ, Demirhan E, Hughes TP, Kantarjian HM, le Coutre PD. Population pharmacokinetic and exposure-response analysis of nilotinib in patients with newly diagnosed Ph+ chronic myeloid leukemia in chronic phase. Eur J Clin Pharmacol. 2012 May;68(5):723-33. doi: 10.1007/s00228-011-1200-7. Epub 2011 Dec 30.
• Kantarjian HM, Hochhaus A, Saglio G, De Souza C, Flinn IW, Stenke L, Goh YT, Rosti G, Nakamae H, Gallagher NJ, Hoenekopp A, Blakesley RE, Larson RA, Hughes TP. Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. Lancet Oncol. 2011 Sep;12(9):841-51. doi: 10.1016/S1470-2045(11)70201-7. Epub 2011 Aug 17. Erratum In: Lancet Oncol. 2011 Oct;12(11):989.
• Cortes JE, Hochhaus A, le Coutre PD, Rosti G, Pinilla-Ibarz J, Jabbour E, Gillis K, Woodman RC, Blakesley RE, Giles FJ, Kantarjian HM, Baccarani M. Minimal cross-intolerance with nilotinib in patients with chronic myeloid leukemia in chronic or accelerated phase who are intolerant to imatinib. Blood. 2011 May 26;117(21):5600-6. doi: 10.1182/blood-2010-11-318949. Epub 2011 Apr 5.
• Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, Pasquini R, Clark RE, Hochhaus A, Hughes TP, Gallagher N, Hoenekopp A, Dong M, Haque A, Larson RA, Kantarjian HM; ENESTnd Investigators. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010 Jun 17;362(24):2251-9. doi: 10.1056/NEJMoa0912614. Epub 2010 Jun 5.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 25, 2019): 846
• Original Estimated Enrollment (submitted: May 9, 2007): 771
• Actual Study Completion Date: August 21, 2019
• Actual Primary Completion Date: September 2, 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion criteria:

• Chronic myelogenous leukemia in chronic phase patients within the first 6 months of diagnosis.
• Diagnosis of chronic myelogenous leukemia in chronic phase with confirmation of Philadelphia chromosome of (9:22) translocations

Key Exclusion criteria:

• Previously documented T315I mutation
• Treatment with a tyrosine kinase inhibitor prior to study entry is not allowed except for no more than 2 weeks in duration of imatinib
• Any medical treatment for CML prior to study entry for longer than 2 weeks with the exception of hydroxyurea and/or anagrelide
• Impaired cardiac function.
• Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection).
• Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol, phenprocoumon)
• Currently receiving treatment with any medications that have the potential to prolong the QT interval.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Austria, Belgium, Brazil, Canada, Colombia, Czechia, Denmark, Egypt, Finland, France, Germany, Hong Kong, Hungary, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, Norway, Poland, Russian Federation, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States, Venezuela
• Removed Location Countries: Algeria, Czech Republic, Portugal

Administrative Information

• NCT Number: NCT00471497
• Other Study ID Numbers: CAMN107A2303; 2007-000208-34 ( Registry Identifier: EUDRACT )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Not Provided
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Novartis
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: October 2020