Aplastic Anemias, Bone Marrow Failure Syndromes, Non-severe Aplastic Anemia, Severe Aplastic Anemia, Refractory, Severe Aplastic Anemia, Relapse, Severe Aplastic Anemia (SAA)
Conditions
Keywords
DR-01, Dibotatug, aplastic anemia, transfusion dependent, hematologic diseases, hematology, Blood disorder, pancytopenia, stem cell disorder, red blood cell disease, white blood cell disease
Brief summary
This is a multicenter, open-label, Phase 1/2 basket study to evaluate the safety and efficacy of Dibotatug (DR-01) in adults with Bone Marrow Failure syndromes.
Detailed description
Study DR-01-HEM-001 is an open-label Phase 1/2 study evaluating the safety and efficacy of dibotatug in adult patients with BMF syndromes. Participants will be enrolled across three cohorts. Cohort A includes relapsed Severe Aplastic Anemia participants, Cohort B includes refractory Severe Aplastic Anemia participants, and Cohort C includes relapsed or refractory transfusion dependent Nonsevere Aplastic Anemia participants. Stage 1 will evaluate the safety and preliminary efficacy in up to 12 evaluable participants, and if deemed appropriate by a Safety Review Committee, the study will continue to enroll in Stage 2 for a total of up to 60 participants.
Interventions
DRUGDibotatug (DR-01)
Dibotatug (DR-01) administered by IV infusion
Sponsors
Dren Bio
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single Arm Basket trial - 3 cohorts will receive the same treatment paradigm in parallel
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years old * Women of childbearing potential and males must agree to use 2 methods of effective contraception, with at least 1 method being highly effective. Inclusion Criteria for Severe Aplastic Anemia (SAA) (Cohorts A and B): * Participants with SAA must have a current or prior diagnosis of SAA or very SAA. Inclusion Criteria for Refractory Severe Aplastic Anemia (Cohort A) Participants with refractory SAA must have: * Received one ≥ 3-month course of ATG and/or CSA-based IST. * Refractory SAA, defined as failure to achieve CR or PR ≥ 3 months after starting ATG and/or CSA-based IST. Inclusion Criteria for Relapsed Severe Aplastic Anemia (Cohort B): * Relapsed SAA, defined as relapse following a CR or PR that was achieved ≥ 3 months after starting ATG- and/or cyclosporine A (CSA)-based IST. Inclusion Criteria for Relapsed or Refractory Transfusion-Dependent Non-Severe Aplastic Anemia (Cohort C): * Current or prior diagnosis of NSAA * No current or prior diagnosis of SAA. * Received at least 1 prior course of IST such as ATG- or CSA, with or without a TPO-R agonist (lasting ≥ 3 months). * Meets criteria for transfusion dependence (either RBC or platelet): * RBC transfusion dependence: transfusion of ≥ 2 units of RBCs in the past 56 days * Platelet transfusion dependence: transfusion of ≥ 1 unit of apheresis platelets in the past 28 days Participants entering the Extension Treatment Period must meet the following criteria: * Signed informed consent form (ICF) for the Extension Treatment Period. * CR or PR by Week 24 during the Main Treatment Period
Exclusion criteria
* Diagnosis of Fanconi anemia, dyskeratosis congenita, or other congenital BMF syndrome. * Prior HCT. * Planning to receive HCT as treatment for AA. * Evidence of a clonal disorder with poor risk cytogenetics per Revised International Prognostic Scoring System (IPSS-R) for MDS. * Diagnosis of PNH or a clonal hematologic bone marrow disorder such as LGLL. Existence of PNH clones, LGLL cells, or clonal hematopoiesis of indeterminate potential (CHIP) clones without a clinical diagnosis is not exclusionary. * Use of a T-cell depleting agent (e.g., ATG, alemtuzumab, thymoglobulin) within 3 months prior to Day 1. * Use of a B-cell depleting agent (e.g., rituximab, ocrelizumab, ofatumumab, ublituximab) within 28 days prior to Day 1. * Use of any of the following within 14 days of Day 1, unless used as an established therapy at screening and there is evidence of either progressive cytopenia or lack of count improvement over the 3 months before screening: * Calcineurin inhibitor (e.g., cyclosporine), TPO-R agonist (e.g., eltrombopag), Androgen (e.g., danazol), Oral Janus kinase (JAK) inhibitor * Regardless of their use as an established therapy at screening, use of the above medications is prohibited for all participants from 3 months after Day 1. * Current infection not adequately responding to appropriate therapy or requiring hospitalization. * Current uncontrolled or invasive infection with cytomegalovirus (CMV), Epstein Barr virus (EBV), varicella zoster virus (VZV), herpes simplex virus (HSV), or human T-lymphotropic virus-1 (HTLV-1), defined by polymerase chain reaction (PCR) at screening. Note that low level CMV, EBV, or VZV viremia is not exclusionary. * Human immunodeficiency virus (HIV) infection. * Current or prior infection with hepatitis B virus (HBV) * Current hepatitis C virus (HCV) infection * Latent tuberculosis (TB) infection as indicated by IFN-γ release assay without documentation of appropriate treatment (appropriate therapy as defined by the World Health Organization \[WHO\] and/or the United States Centers for Disease Control and Prevention). * Estimated glomerular filtration rate \< 30 mL/min/1.73 m2 at screening (using the Chronic Kidney Disease Epidemiology Collaboration formula; Levey 2009). * Total bilirubin \> 1.5 × upper limit of normal (ULN) (\> 3 × ULN if known Gilbert's disease). * Aspartate aminotransferase or alanine aminotransferase \> 2.5 × ULN (except in participants with known iron overload).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate of Dibotatug (defined as proportion of subjects with a Complete Response or Partial Response) [Efficacy] | By 6 months | Overall Response Rate (ORR), defined as the proportion of subjects with Complete Response (CR) or Partial Response (PR) based on disease-specific response criteria. |
| Incidence and severity of adverse events as assessed by CTCAE v6.0 [Safety and Tolerability] | 52 weeks | Incidence and severity of adverse events as assessed by CTCAE v6.0. |
Countries
United States
Contacts
CONTACTDren Bio Central Contact
STUDY_DIRECTORWan-Jen Hong, MD
Dren Bio
Outcome results
None listed