Dibotatug in adults with bone marrow failure syndromes

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a multicenter, open-label Phase 1/2 basket trial evaluating the safety and early signs of efficacy of dibotatug (DR-01) in adults with bone marrow failure syndromes. Participants are enrolled in three cohorts: refractory severe aplastic anemia, relapsed severe aplastic anemia, and relapsed or refractory transfusion-dependent non-severe aplastic anemia. The study starts with a safety and preliminary efficacy assessment in at least 12 evaluable participants, with potential expansion to up to 60 participants total across cohorts if a Safety Review Committee approves. The intervention is dibotatug (DR-01).

Why it matters

Who can join: the full rules

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).

Where it's running

• Dren Investigational Site
  Atlanta, Georgia, United States Recruiting
• Dren Investigational Site
  New York, New York, United States Recruiting
• Dren Investigational Site
  Duarte, California, United States Not yet recruiting
• Dren Investigational Site
  Palo Alto, California, United States Not yet recruiting
• Dren Investigational Site
  Miami, Florida, United States Not yet recruiting
• Dren Investigational Site
  Cleveland, Ohio, United States Not yet recruiting

Study contacts

• Study coordinator: Dren Bio Central Contact
• Email: DR-01-HEM-001_inquiries@drenbio.com
• Phone: 415-737-5277

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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• Using umbilical cord blood to support stem cell transplants for treating aplastic anemia

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.