Dose Escalation and Dose Expansion Study of Tirabrutinib in Combination With Other Targeted Anti-cancer Therapies in Adults With B-cell Malignancies

NCT02457598 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: GS-US-401-17572015-000834-30
• Study Type: interventional
• Target: 203
• Locations: 3 countries
• Sites: 15

Brief Summary

The primary objectives of this study are to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of tirabrutinib (ONO/GS-4059) in combination with other targeted anti-cancer therapies and to evaluate the long-term safety of tirabrutinib as a monotherapy and in combination with other targeted anti-cancer therapies in adults with relapsed or refractory B-cell lymphoproliferative malignancies. This study consists of three parts: Dose Escalation, Dose Expansion, and Long-term Safety Monitoring. During the Dose Escalation phase, participants will be sequentially enrolled in a standard 3 + 3 dose escalation study design, to receive oral tirabrutinib combined with idelalisib entospletinib +/- obinutuzumab. The Dose Expansion Phase will enroll additional participants with a single B-cell lymphoproliferative malignancy disease type to further evaluate efficacy, safety, tolerability, PK, and pharmacodynamics. The Long-term Safety Monitoring phase will evaluate the long-term safety of tirabrutinib both as a monotherapy and in combination with other anti-cancer therapies. As of Amendment 9, all participants currently on the study who have no clinical evidence of disease progression will transition into long-term safety monitoring. Participants from the ongoing Study GS-US-401-1787 and participants who came off Study GS-US-401-1757 and Study GS-US-401-1787 but continued to receive treatment via named patient use (or individual expanded use) will be enrolled into the long-term safety monitoring group (Group VI). Participants enrolled in Group VI will continue the same treatment regimen in Study GS-US-401-1787 or named patient use (or individual expanded use). As of Protocol Amendment 8, the maximum treatment duration for any participant is an additional 6 years from the date of this amendment (ie. until November 2025). As of Amendment 9, entospletinib will be provided until 31 December 2020 to participants who are currently receiving entospletinib. Participants treated with entospletinib as part of a combination regimen with tirabrutinib will stop receiving entospletinib by 31 December 2020 but may continue to be treated with tirabrutinib monotherapy. Idelalisib will be provided as 50 mg tablets until 31 December 2020 and 100 mg tablets until study completion. Participants assigned to the 50 mg tablet will be given the option, at the investigator's discretion, to switch to 100 mg once daily idelalisib dose.

Conditions

B-cell Malignancies

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants With Dose Limiting Toxicities (DLTs)

  A DLT was defined as a ≥ Grade 3 AE that was assessed as related to study drug that occurred during the 28-day DLT assessment period with protocol-defined allowed exceptions. Any treatment-emergent adverse event (TEAE) that was, in the opinion of the Clinical Trial Steering Committee, of potential clinical significance such that further dosing exposed participants to unacceptable risk, was considered a DLT.

  Up to 28 days

• Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) at Week 12 in Participants With Non-Chronic Lymphocytic Leukemia (CLL) Type NHL

  ORR for Waldenstrom Macroglobulinemia(WM):CR+VGPR+PR+MPR. CR: Absence of serum monoclonal IgM protein; normal serum IgM level: complete resolution of extramedullary disease, morphologically normal bone marrow/aspirate and trephine biopsy. Very good partial response (VGPR):Detectable monoclonal IgM; ≥90% reduction in serum IgM; Complete resolution of extramedullary disease; No new signs/symptoms. PR: Monoclonal immunoglobulin M (IgM) protein is detectable ≥50% but \<90% reduction in serum IgM level from baseline; reduction of extramedullary disease; no new signs or symptoms of active disease. Minor response (MPR):Detectable monoclonal IgM; ≥25% but \<50% reduction in serum IgM; No progression of extramedullary disease; No new signs/symptoms. Clopper-Pearson method was used in analysis. Data is reported by disease type: WM; Follicular Lymphoma (FL);Mantle Cell Lymphoma (MCL);Small Lymphocytic Lymphoma (SLL);Marginal Zone Lymphoma (MZL);Diffuse Large B-Cell Lymphoma (DLBCL) as applicable.

  Week 12

• ORR: Percentage of Participants With CR or PR in Participants With CLL at Week 24

  ORR was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR). CR and PR are defined in outcome measure#2. Clopper-Pearson method was used in outcome measure analysis. Percentages were rounded off.

  Week 24

• Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)

  An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. TEAEs were defined as an AE that onset in the period from the first dose of study treatment to 30 days after the last dose of study treatment. Percentages were rounded off.

  First dose up to last dose date (up to 441 weeks) plus 30 days

Secondary Outcomes (13)

• ORR: Percentage of Participants With Complete Response (CR) or Partial Response (PR) in the Dose Escalation and Expansion Phase

  Up to 281 weeks

• Progression Free Survival (PFS) During the Dose Escalation Phase and Dose Expansion Phase

  Up to 281 weeks

• Duration of Response (DOR) During the Dose Escalation Phase and Dose Expansion Phase

  Up to 281 weeks

• Time to Response (TTR) During the Dose Escalation Phase and Dose Expansion Phase

  Up to 281 weeks

• Percentage of Participants Who Achieved Minimal Residual Negative Disease (< 1 Leukemia Cell/10,000 Leukocytes) During the Dose Escalation Phase and Dose Expansion Phase in Participants With CLL

  Up to 281 weeks

Study Arms (17)

Combination I (Tirabrutinib 20 mg QD+ Idelalisib 50 mg BID)

EXPERIMENTAL

Participants will receive tirabrutinib 20 mg tablet once daily (QD) for up to 209 weeks and idelalisib 50 mg tablet twice daily (BID) orally for up to 120 weeks. Both drugs will be administered for 28-day cycles.

Drug: Tirabrutinib; Drug: Idelalisib

Combination I (Tirabrutinib 40 mg QD+ Idelalisib 50 mg BID)

EXPERIMENTAL

Participants will receive tirabrutinib 40 mg tablet QD for up to 251 weeks and idelalisib 50 mg tablet BID orally, for up to 245 weeks. Both drugs will be administered for 28-day cycles.

Drug: Tirabrutinib; Drug: Idelalisib

Combination I (Tirabrutinib 80 mg QD+ Idelalisib 50 mg BID)

EXPERIMENTAL

Participants will receive tirabrutinib 80 mg tablet QD for up to 212 weeks and idelalisib 50 mg tablet BID orally, for up to 26 weeks. Both drugs will be administered for 28-day cycles.

Drug: Tirabrutinib; Drug: Idelalisib

Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD)

EXPERIMENTAL

Participants will receive tirabrutinib 80 mg tablet QD for up to 227 weeks and idelalisib 100 mg tablet QD orally, for up to 227 weeks. Both drugs will be administered for 28-day cycles.

Drug: Tirabrutinib; Drug: Idelalisib

Combination I (Tirabrutinib 160 mg QD+ Idelalisib 100 mg QD)

EXPERIMENTAL

Participants will receive tirabrutinib 160 mg tablet QD for up to 151 weeks and idelalisib 100 mg tablet QD orally, for up to 151 weeks. Both drugs will be administered for 28-day cycles.

Drug: Tirabrutinib; Drug: Idelalisib

Combination I (Tirabrutinib 20 mg BID+ Idelalisib 50 mg BID)

EXPERIMENTAL

Participants will receive tirabrutinib 20 mg tablet BID for up to 207 weeks and idelalisib 50 mg tablet BID orally, for up to 207 weeks. Both drugs will be administered for 28-day cycles.

Drug: Tirabrutinib; Drug: Idelalisib

Combination II (Tirabrutinib 40 mg QD+ Entospletinib 200 mg QD)

EXPERIMENTAL

Participants will receive tirabrutinib 40 mg tablet QD for up to 250 weeks and entospletinib 200 mg tablet QD orally, for up to 250 weeks. Both drugs will be administered for 28-day cycles.

Drug: Tirabrutinib; Drug: Entospletinib

Combination II (Tirabrutinib 80 mg QD+ Entospletinib 200 mg QD)

EXPERIMENTAL

Participants will receive tirabrutinib 80 mg tablet QD for up to 234 weeks and entospletinib 200 mg tablet QD orally, for up to 220 weeks. Both drugs will be administered for 28-day cycles.

Drug: Tirabrutinib; Drug: Entospletinib

Combination II (Tirabrutinib 150 mg QD+ Entospletinib 200 mg QD)

EXPERIMENTAL

Participants will receive tirabrutinib 150 mg tablet QD for up to 103 weeks and entospletinib 200 mg tablet QD orally, for up to 88 weeks. Both drugs will be administered for 28-day cycles.

Drug: Tirabrutinib; Drug: Entospletinib

Combination II (Tirabrutinib 40 mg QD+ Entospletinib 400 mg QD)

EXPERIMENTAL

Participants will receive tirabrutinib 40 mg tablet QD for up to 119 weeks and entospletinib 400 mg tablet QD orally, for up to 119 weeks. Both drugs will be administered for 28-day cycles.

Drug: Tirabrutinib; Drug: Entospletinib

Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD)

EXPERIMENTAL

Participants will receive tirabrutinib 80 mg tablet QD for up to 232 weeks and entospletinib 400 mg tablet QD orally, for up to 229 weeks. Both drugs will be administered for 28-day cycles.

Drug: Tirabrutinib; Drug: Entospletinib

Combination II (Tirabrutinib 160 mg QD+ Entospletinib 400 mg QD)

EXPERIMENTAL

Participants will receive tirabrutinib 160 mg tablet QD for up to 44 weeks and entospletinib 400 mg tablet QD orally, for up to 44 weeks. Both drugs will be administered for 28-day cycles.

Drug: Tirabrutinib; Drug: Entospletinib

Combination III (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD+ obinutuzumab 1000 mg)

EXPERIMENTAL

Participants will receive tirabrutinib 80 mg tablet QD for up to 199 weeks; Idelalisib 100 mg tablet QD orally for up to 199 weeks, and single dose of obinutuzumab 1000 mg intravenously (IV) for up to 22 weeks. Both drugs will be administered for 28-day cycles.

Drug: Tirabrutinib; Drug: Idelalisib; Drug: Obinutuzumab

Combination IV (Tirabrutinib 80 mg QD+ entospletinib 400 mg QD+ obinutuzumab 1000 mg)

EXPERIMENTAL

Participants will receive tirabrutinib 80 mg tablet QD for up to 196 weeks; entospletinib 400 mg tablet QD orally for up to 196 weeks and single dose of obinutuzumab 1000 mg IV for up to 22 weeks. Both drugs will be administered for 28-day cycles.

Drug: Tirabrutinib; Drug: Entospletinib; Drug: Obinutuzumab

Group V Single Agent Tirabrutinib

EXPERIMENTAL

Participants will receive tirabrutinib 80 mg tablet QD orally, for each 28-day cycle up to 194 weeks.

Drug: Tirabrutinib

Group VI Single Agent Tirabrutinib: CLL

EXPERIMENTAL

Participants with CLL who received tirabrutinib in this or a previous tirabrutinib study will continue to receive tirabrutinib at the original dose (between the range of 40 - 400 mg), tablet QD, for each 28-day cycle up to 441 weeks. Participants will be monitored for the long-term safety of tirabrutinib in this group.

Drug: Tirabrutinib

Group VI Single Agent Tirabrutinib: NHL

EXPERIMENTAL

Participants with NHL who received tirabrutinib in this or a previous tirabrutinib study will continue to receive tirabrutinib at the original dose (between the range of 60 - 480 mg), tablet QD, for each 28-day cycle up to 441 weeks. Participants will be monitored for the long-term safety of tirabrutinib in this group.

Drug: Tirabrutinib

Interventions

Tirabrutinib DRUG

Capsules or tablets administered orally

Also known as: ONO/GS-4059

Combination I (Tirabrutinib 160 mg QD+ Idelalisib 100 mg QD); Combination I (Tirabrutinib 20 mg BID+ Idelalisib 50 mg BID); Combination I (Tirabrutinib 20 mg QD+ Idelalisib 50 mg BID); Combination I (Tirabrutinib 40 mg QD+ Idelalisib 50 mg BID); Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD); Combination I (Tirabrutinib 80 mg QD+ Idelalisib 50 mg BID); Combination II (Tirabrutinib 150 mg QD+ Entospletinib 200 mg QD); Combination II (Tirabrutinib 160 mg QD+ Entospletinib 400 mg QD); Combination II (Tirabrutinib 40 mg QD+ Entospletinib 200 mg QD); Combination II (Tirabrutinib 40 mg QD+ Entospletinib 400 mg QD); Combination II (Tirabrutinib 80 mg QD+ Entospletinib 200 mg QD); Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD); Combination III (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD+ obinutuzumab 1000 mg); Combination IV (Tirabrutinib 80 mg QD+ entospletinib 400 mg QD+ obinutuzumab 1000 mg); Group V Single Agent Tirabrutinib; Group VI Single Agent Tirabrutinib: CLL; Group VI Single Agent Tirabrutinib: NHL

Idelalisib DRUG

Tablets administered orally twice daily

Also known as: Zydelig®, GS-1101, CAL-101

Combination I (Tirabrutinib 160 mg QD+ Idelalisib 100 mg QD); Combination I (Tirabrutinib 20 mg BID+ Idelalisib 50 mg BID); Combination I (Tirabrutinib 20 mg QD+ Idelalisib 50 mg BID); Combination I (Tirabrutinib 40 mg QD+ Idelalisib 50 mg BID); Combination I (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD); Combination I (Tirabrutinib 80 mg QD+ Idelalisib 50 mg BID); Combination III (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD+ obinutuzumab 1000 mg)

Entospletinib DRUG

Tablets administered orally

Also known as: GS-9973

Combination II (Tirabrutinib 150 mg QD+ Entospletinib 200 mg QD); Combination II (Tirabrutinib 160 mg QD+ Entospletinib 400 mg QD); Combination II (Tirabrutinib 40 mg QD+ Entospletinib 200 mg QD); Combination II (Tirabrutinib 40 mg QD+ Entospletinib 400 mg QD); Combination II (Tirabrutinib 80 mg QD+ Entospletinib 200 mg QD); Combination II (Tirabrutinib 80 mg QD+ Entospletinib 400 mg QD); Combination IV (Tirabrutinib 80 mg QD+ entospletinib 400 mg QD+ obinutuzumab 1000 mg)

Obinutuzumab DRUG

Administered intravenously

Combination III (Tirabrutinib 80 mg QD+ Idelalisib 100 mg QD+ obinutuzumab 1000 mg); Combination IV (Tirabrutinib 80 mg QD+ entospletinib 400 mg QD+ obinutuzumab 1000 mg)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), chronic lymphocytic leukemia (CLL) (meeting International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria 2008), mantle cell lymphoma (MCL), Waldenstrom's macroglobulinemia (WM), or non-germinal center B-cell lymphoma (GCB) diffuse large B-cell lymphoma (DLBCL) as documented by medical records on World Health Organization (WHO) criteria
• Prior treatment for FL, MZL, SLL, MCL, WM with ≥ 2 or for CLL or non-GCB DLBCL ≥ 1 chemotherapy-based or immunotherapy-based regimen, and not transplant eligible and have had either progressive disease (PD) or no response to previous treatment
• For diseases other than Waldenstrom's macroglobulinemia (WM), presence of radiographically measurable presence of ≥ 1 lesion that measures ≥ 2.0 cm in the longest dimension (LD) and ≥ 1.0 cm in the longest perpendicular dimension (LPD)
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Platelets ≥ 50 x 10\^9/L; Hb ≥ 8.0 g/dL; absolute neutrophil count (ANC) ≥ 1.0 x 10\^9/L
• Without transfusion and growth factors within 7 days
• Aspartate transaminase/alanine transaminase (AST/ALT) ≤ 2.5 x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 x ULN
• Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 60 mL/min
• Not pregnant
• Willingness and ability to comply with protocol-specified Pneumocystis jirovecii pneumonia (PJP) prophylaxis
• Long-term Safety Monitoring group only (Group VI):
• Currently enrolled in Study GS-US-401-1787 or previously enrolled in Study GS-US-401-1757 or Study GS-US-401-1787 and currently receiving continued treatment via named patient use
• Continuing to benefit from the current treatment regimen in the opinion of the investigator/treating physician

You may not qualify if:

• Hepatitis B surface antigen (HBsAG) positive or hepatitis B core antibody positive
• Hepatitis C virus (HCV) antibody positive
• History of long QT syndrome or whose corrected QT(QTc) interval measured (Fridericia method) at screening is prolonged (\>450 ms)
• Long-term Safety Monitoring group only (Group VI):
• Evidence of clinical or radiological disease progression

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (15)

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Indiana University Health Goshen Center for Cancer Care

Goshen, Indiana, 46506, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

CHRU de Lille, Hopital Claude Huriez

Lille, 59037, France

Location

Hopital Saint Eloi

Montpellier, 34295, France

Location

Chu Haut Leveque

Pessac, 33604, France

Location

Centre Hospitalier de Lyon Sud

Pierre-Bénite, 69310, France

Location

Institut Universitaire du Cancer-Oncopole I.U.C.T-O

Toulouse, 3110, France

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB20QQ, United Kingdom

Location

Cardiff and Vale Health Board, Clinical Research Facility

Cardiff, CF14 4XW, United Kingdom

Location

Leeds Teaching Hosptials NHS Trust, Dept of Haematology

Leeds, LS9 7TF, United Kingdom

Location

University Hospitals of Leicester NHS Trust

Leicester, LE1 5WW, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Plymouth Hospitals NHS Trust

Plymouth, PL68DH, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (8)

• Danilov AV, Herbaux C, Walter HS, Hillmen P, Rule SA, Kio EA, Karlin L, Dyer MJS, Mitra SS, Yi PC, Humeniuk R, Huang X, Zhou Z, Bhargava P, Jurgensmeier JM, Fegan CD. Phase Ib Study of Tirabrutinib in Combination with Idelalisib or Entospletinib in Previously Treated Chronic Lymphocytic Leukemia. Clin Cancer Res. 2020 Jun 15;26(12):2810-2818. doi: 10.1158/1078-0432.CCR-19-3504. Epub 2020 Mar 10.

  PMID: 32156743 BACKGROUND

• Morschhauser F, Dyer MJS, Walter HS, Danilov AV, Ysebaert L, Hodson DJ, Fegan C, Rule SA, Radford J, Cartron G, Bouabdallah K, Davies AJ, Spurgeon S, Rajakumaraswamy N, Li B, Humeniuk R, Huang X, Bhargava P, Jurgensmeier JM, Salles G. Phase 1b study of tirabrutinib in combination with idelalisib or entospletinib in previously treated B-cell lymphoma. Leukemia. 2021 Jul;35(7):2108-2113. doi: 10.1038/s41375-020-01108-x. Epub 2020 Dec 17. No abstract available.

  PMID: 33328591 BACKGROUND

• Salles, G., Dyer, MJS,. Hodson, DJ., et-al. Updated Preliminary Results of a Phase 1b Dose Escalation and Dose Expansion Study of Tirabrutinib in Combination with Entospletinib in Patients with B-Cell Lymphoma. Blood 2018; 132 (Supplement 1): 5344.

  BACKGROUND

• Walter HS, Rule SA, Dyer MJ, Karlin L, Jones C, Cazin B, Quittet P, Shah N, Hutchinson CV, Honda H, Duffy K, Birkett J, Jamieson V, Courtenay-Luck N, Yoshizawa T, Sharpe J, Ohno T, Abe S, Nishimura A, Cartron G, Morschhauser F, Fegan C, Salles G. A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies. Blood. 2016 Jan 28;127(4):411-9. doi: 10.1182/blood-2015-08-664086. Epub 2015 Nov 5.

  PMID: 26542378 BACKGROUND

• Walter HS, Salles GA, Dyer MJ. New Agents to Treat Chronic Lymphocytic Leukemia. N Engl J Med. 2016 Jun 2;374(22):2185-6. doi: 10.1056/NEJMc1602674. No abstract available.

  PMID: 27248633 BACKGROUND

• Morschhauser, F., Radford, J., Ysebaert, L., et-al. Updated Preliminary Results of a Phase 1b Dose Escalation and Dose Expansion Study of Tirabrutinib in Combination with Idelalisib in Patients with B-Cell Lymphoma. Blood 2018; 132 (Supplement 1): 5345.

  BACKGROUND

• Walter HS, Jayne S, Rule SA, Cartron G, Morschhauser F, Macip S, Karlin L, Jones C, Herbaux C, Quittet P, Shah N, Hutchinson CV, Fegan C, Yang Y, Mitra S, Salles G, Dyer MJS. Long-term follow-up of patients with CLL treated with the selective Bruton's tyrosine kinase inhibitor ONO/GS-4059. Blood. 2017 May 18;129(20):2808-2810. doi: 10.1182/blood-2017-02-765115. Epub 2017 Apr 4. No abstract available.

  PMID: 28377400 BACKGROUND

• Yahiaoui A, Meadows SA, Sorensen RA, Cui ZH, Keegan KS, Brockett R, Chen G, Queva C, Li L, Tannheimer SL. PI3Kdelta inhibitor idelalisib in combination with BTK inhibitor ONO/GS-4059 in diffuse large B cell lymphoma with acquired resistance to PI3Kdelta and BTK inhibitors. PLoS One. 2017 Feb 8;12(2):e0171221. doi: 10.1371/journal.pone.0171221. eCollection 2017.

  PMID: 28178345 DERIVED

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

tirabrutinib; idelalisib; 6-(1H-indazol-6-yl)-N-(4-morpholinophenyl)imidazo(1,2-a)pyrazin-8-amine; obinutuzumab

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Enrollment and treatment were parallel in different combinations used in the study.

Study Record Dates

• First Submitted: May 27, 2015
• First Posted: May 29, 2015
• Study Start: June 16, 2015
• Primary Completion: September 25, 2024
• Study Completion: September 25, 2024
• Last Updated: June 17, 2025
• Results First Posted: June 17, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (7); US (3); FR (5)