A Phase 2, Multicenter Study to Evaluate the Efficacy and Safety of BN101 in Subject With Chronic Graft Versus Host Disease (cGVHD) After at Least Fist Line of Systemic Therapy
Overview
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 30
- Locations
- 7
- Primary Endpoint
- Overall Response Rate (ORR)
Overview
Brief Summary
This is a phase 2, open-label, multicenter trial to evaluate the efficacy and safety of BN101 in subjects with Chronic Graft Versus Host Disease (cGVHD) after at least First Line of systemic therapy.
Detailed Description
Approximately 30 subjects will be enrolled to receive orally administered BN101 200 mg QD (once daily)
Study drug will be administered in 28-day cycles until disease progression or unacceptable toxicity. Subjects may receive study drug in the inpatient or outpatient setting.
Curative Effect analysis The efficacy was analyzed based on MITT The point estimate and 95%CI of ORR were calculated based on the exact probability method of binomial distribution.If applicable, a logistic regression model will be used for multivariate analysis.
Descriptive statistical analyses were provided for all secondary efficacy endpoints.
The following subgroups will be analysed:
- Severe cGVHD (Yes/No)
- Number of organs involved (<4 vs. ≥4)
- Number of previous systemic cGVHD treatment (1 vs. ≥2)
- Duration of cGVHD before inclusion (i.e., from the time of cGVHD diagnosis to the time of inclusion)
- Lung Involvement (Yes/No)
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Male and female subjects at least 18 years of age who have had allogenic hematopoietic cell transplant (HCT).
- •Previously received at least 1 and not more than 5 lines of systemic therapy for cGVHD
- •Receiving glucocorticoid therapy with a stable dose over the 2 weeks prior to screening;
- •Have persistent cGVHD manifestations and systemic therapy is indicated
Exclusion Criteria
- •Subject has not been on a stable dose / regimen of systemic cGVHD treatments for at least 2 weeks prior to screening. (Note: Concomitant corticosteroids, calcineurin inhibitors, sirolimus, MMF, methotrexate, rituximab, and extracorporeal photophoresis (ECP) are acceptable. Systemic investigational GVHD treatments are not permitted).
- •Histological relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.
- •Current treatment with ibrutinib. Prior treatment with ibrutinib is allowed with a washout of at least 28 days prior to treatment.
Arms & Interventions
200mg qd
200mg qd po.
Intervention: BN101 (Drug)
Outcomes
Primary Outcomes
Overall Response Rate (ORR)
Time Frame: 12 Months
OR was defined as the percentage of participants with complete response (CR) or partial response (PR). The OR determination of chronic graft versus host disease (cGVHD) was based on cGVHD response assessment performed by clinicians as per the 2014 National Institutes of Health (NIH) Consensus Development Project for Clinical Trials in cGVHD criteria. CR was defined as the resolution of all manifestations in each organ or site. PR was defined as the improvement in at least 1 organ or site without progression in any other organ or site; and cGVHD progression was defined as the clinically meaningful worsening in 1 or more organs regardless of improvement in other organs.
Secondary Outcomes
- Duration of Response (DOR)(12 Months)
- Time-to-Response (TTR)(12 months)
- Number of Participants With Best Response in Each Individual Organ(12 months)
- Number of Participants With Change From Baseline in Overall Score on Lee cGvHD Symptom Scale at Specified Time Points(Baseline and 12 months)
- Failure-free Survival (FFS)(12 months)
- Time to Next Therapy (TTNT)(12months)
- Overall Survival (OS)(12months)
- Change From Baseline in Corticosteroids Dose(12months)
- Number of Participants With Change From Baseline in Calcineurin Inhibitor (CNI) Usage.(12months)
- Change From Baseline in in Global Severity Rating (GSR) Score by Clinician-reported cGVHD Assessment(12months)
- Change From Baseline in Symptom Activity by cGVHD Activity Assessment Participant Self-Report(12months)