Study of ME-401 in Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma

• ClinicalTrials.gov Identifier: NCT03985189
• Recruitment Status: Active, not recruiting
• First Posted: June 13, 2019
• Last Update Posted: April 13, 2023
• Sponsor: Kyowa Kirin Co., Ltd.
• Information provided by (Responsible Party): Kyowa Kirin Co., Ltd.

Tracking Information

• First Submitted Date: June 5, 2019
• First Posted Date: June 13, 2019
• Last Update Posted Date: April 13, 2023
• Actual Study Start Date: April 29, 2019
• Estimated Primary Completion Date: September 30, 2024 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 12, 2019): Number of participants with treatment-emergent adverse events (TEAEs) [ Time Frame: Up to approximately 1 year ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 11, 2023)

• [Phase 1 study (DLT evaluation)] Plasma concentration level of ME-401 [ Time Frame: Up to approximately 2 years ]
• [Phase 1 study (DLT evaluation)] Maximum plasma drug concentration (Cmax) [ Time Frame: Up to approximately 2 years ]
• [Phase 1 study (DLT evaluation)] Area under the plasma drug concentration time curve (AUC) [ Time Frame: Up to approximately 2 years ]
• [Phase 1 study (DLT evaluation)] Terminal half-life (t1/2) [ Time Frame: Up to approximately 2 years ]
• [Phase 1 study (DLT evaluation)] Efficacy of ME-401 as assessed by the objective response rate (ORR) [ Time Frame: Up to approximately 2 years ]
• [Phase 1 study (DLT evaluation)] Efficacy of ME-401 will be assessed by the duration of response (DOR) [ Time Frame: Up to approximately 2 years ]
• [Phase 1 study (DLT evaluation)] Efficacy of ME-401 will be assessed by the progression-free survival (PFS) [ Time Frame: Up to approximately 2 years ]
• [Phase 1 study (DLT evaluation)] Efficacy of ME-401 will be assessed by the time to response (TTR) [ Time Frame: Up to approximately 2 years ]

Original Secondary Outcome Measures (submitted: June 12, 2019)

• Plasma concentration level of ME-401 [ Time Frame: Up to approximately 2 years ]
• Maximum plasma drug concentration (Cmax) [ Time Frame: Up to approximately 2 years ]
• Area under the plasma drug concentration time curve (AUC) [ Time Frame: Up to approximately 2 years ]
• Terminal half-life (t1/2) [ Time Frame: Up to approximately 2 years ]
• Efficacy of ME-401 as assessed by the objective response rate (ORR) [ Time Frame: Up to approximately 2 years ]
• Efficacy of ME-401 will be assessed by the duration of response (DOR) [ Time Frame: Up to approximately 2 years ]
• Efficacy of ME-401 will be assessed by the progression-free survival (PFS) [ Time Frame: Up to approximately 2 years ]
• Efficacy of ME-401 will be assessed by the time to response (TTR) [ Time Frame: Up to approximately 2 years ]

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

Descriptive Information

• Brief Title: Study of ME-401 in Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma
• Official Title: A Japanese Phase 1 Study of ME-401 in Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma and Roll Over Study for Subjects Who Have Participated in ME-401-004 Study
• Brief Summary: The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of ME-401 in the treatment of Japanese participants with Relapsed or Refractory indolent B-Cell Non-Hodgkin's Lymphoma and to continue administraion of ME-401 to patients with relapsed or refractory B-cell NHL with collecting safety information
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma

Intervention

Drug: ME-401

[Phase 1 study (DLT evaluation)] ME-401 will be administered at 2 dosages as 45 mg (Cohort 1) or 60 mg (Cohort 2), daily oral administration, QD, and the trial will be initiated at Cohort 1, and medical specialists and the Efficacy and Safety Assessment Committee as needed will decide whether the Cohort will be shifted to the next stage based on their assessment of the safety and tolerability.

[Roll over study] 60 mg ME-401 will be administrated on intermittent schedule (1 week on and 3 week off in every 4-week cycle)and will continue until the prescribed mediation in ME-401-004 study is completed or discontinuation criteria are met.

Study Arms

Experimental: ME-401

ME-401 administered orally

Intervention: Drug: ME-401

• Publications *: Goto H, Izutsu K, Ennishi D, Mishima Y, Makita S, Kato K, Hanaya M, Hirano S, Narushima K, Teshima T, Nagai H, Ishizawa K. Zandelisib (ME-401) in Japanese patients with relapsed or refractory indolent non-Hodgkin's lymphoma: an open-label, multicenter, dose-escalation phase 1 study. Int J Hematol. 2022 Dec;116(6):911-921. doi: 10.1007/s12185-022-03450-5. Epub 2022 Sep 15.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 11, 2023): 14
• Original Estimated Enrollment (submitted: June 12, 2019): 12
• Estimated Study Completion Date: September 30, 2024
• Estimated Primary Completion Date: September 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

[Phase 1 study (DLT evaluation)]

• Patients aged 20 years or older at the submission of the written informed consent form
• Patients with relapsed or refractory B-cell NHL
• Patients who have not undergone phosphatidylinositol 3-kinase inhibitor (PI3K) to date.
• Patients who have undergone Bruton's tyrosine kinase (BTK) inhibitors and have had no exacerbation during the use of BTK inhibitors.
• Patients with ECOG PS 0 or 1.

Exclusion Criteria:

[Phase 1 study (DLT evaluation)]

• Patients who underwent any major surgical treatment within 4 weeks prior to the initiation of the investigational product.
• Patients with poorly controlled diseases. The followings are the examples but the diseases will not be limited to those.
• Patients in whom any of HBV antigen/antibody, HCV antibody, HIV antibody or HTLV-1 antibody will be positive at screening test.
• Patients with active interstitial lung disease or a history thereof.
• Patients who have received the investigational products other than ME-401, systemic chemotherapy or radiotherapy within 4 weeks prior to the initiation of ME-401.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 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: Japan

Administrative Information

• NCT Number: NCT03985189
• Other Study ID Numbers: ME-401-K01
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Kyowa Kirin Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Kyowa Kirin Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Kyowa Kirin Co., Ltd.
• Verification Date: April 2023