Safety and Efficacy Study of Sotatercept in Adults With Transfusion Dependent Diamond Blackfan Anemia (ACE-011-DBA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by Northwell Health
Sponsor:
Information provided by (Responsible Party):
Adrianna Vlachos, Northwell Health
ClinicalTrials.gov Identifier:
NCT01464164
First received: October 31, 2011
Last updated: June 15, 2016
Last verified: June 2016
  Purpose
The purpose of this study is to determine the safety and dosing of drug Sotatercept, as a subcutaneous injection, to stimulate production of red blood cell production. To be given every 28 days for up to four doses.

Condition Intervention Phase
Diamond Blackfan Anemia
Drug: Sotatercept
Drug: Sotatercept with prednisone boost
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II, Open-Label Study to Determine Safety and Efficacy of Sotatercept (ACE-011) in Adults With Red Blood Cell Transfusion- Dependent Diamond Blackfan Anemia

Resource links provided by NLM:


Further study details as provided by Northwell Health:

Primary Outcome Measures:
  • Determine a safe and effective dose of sotatercept in adults with DBA and RBC transfusion dependence [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    Achieve a complete response transfusion- independent and Hemoglobin >9 gm/dl or a partial response- increase in transfusion interval from baseline and hemoglobin < 9gm/dl iith an increase in reticulocyte count


Secondary Outcome Measures:
  • Safety [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
    Assess type, frequency, and severity of adverse events and relationship to sotatercept according to the currently active minor version of the NCI Common Terminology for Adverse Events version 4.0

  • Time to response [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    Length of time required to achieve a response

  • Response duration [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    Length of time between transfusions

  • Exploratory outcome improvement of bone density [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    Improvement as measured by bone densitometry (DEXA scan)


Estimated Enrollment: 20
Study Start Date: January 2012
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sotatercept
Sotatercept to be given as a subcutaneous injection once a month for 4 consecutive months, using a dose escalation scale among 3 cohorts. *Protocol Amendment: Two additional cohorts will be given Sotatercept as a subcutaneous injection once every 3 weeks.
Drug: Sotatercept

Cohort 4a: 3 patients on Sotatercept 0.75 mg/kg. If the patients have no untoward events in the Patients in Dose Level 4 by the end of 3 of the 6 doses, then additional patients (Dose Level 5) will be enrolled at the next dose level:

Cohort 5a: 3 patients on Sotatercept 1 mg/kg

Other Name: ACE-011
Active Comparator: Sotatercept with prednisone boost
Protocol Amendment: Two additional cohorts will be given Sotatercept as a subcutaneous injection once every 3 weeks along with a prednisone boost.
Drug: Sotatercept with prednisone boost

Cohort 4b: 3 patients on Sotatercept 0.75 mg/kg with a three week prednisone boost. If the patients have no untoward events in the Patients in Dose Level 4 by the end of 3 of the 6 doses, then additional patients (Dose Level 5) will be enrolled at the next dose level:

Cohort 5b: 3 patients on Sotatercept 1 mg/kg with a 3 week prednisone boost.


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • >/= 18 years of age
  • DBA diagnosed
  • RBC transfusion- dependence (defined as >/= 10 cc/kg of RBC per 28 days average)
  • Karnofsky performance scale >/= 70
  • Females of childbearing potential are to use birth control during study participation and for 112 days following the last dose of sotatercept
  • Males must agree to use a latex condom during any sexual contact with females of childbearing potential while participating in the study and for 112 days following the last dose of sotatercept
  • Agreement to adhere to the study visit schedule, understand and comply with all protocol requirements
  • Understand and sign a written informed consent

Exclusion Criteria:

  • Creatinine clearance < 30 ml/min
  • SGOT > 3x upper limit of normal, SGPT > 3x upper limit normal, or bilirubin >3x upper limit normal
  • Heart disease (NY Heart Association classification of >/= 3
  • History of hypertension
  • Subjects currently responsive to corticosteroids for treatment of Diamond Blackfan anemia
  • Treatment with another investigational drug or device <56 days pre-study entry
  • Pregnant or lactating females
  • Cancer
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01464164

Contacts
Contact: Eva Atsidaftos, MA, CCRC 516-562-1504 eatsidaf@northwell.edu
Contact: Jessica Kang, BA 516-562-1505

Locations
United States, New York
North Shore- LIJ campus of The Feinstein Institute for Medical Research Recruiting
Manhasset, New York, United States, 11030
Contact: Eva Atsidaftos, MA    516-562-1504    eatsidaf@northwell.edu   
Principal Investigator: Adrianna Vlachos, MD         
Principal Investigator: Johnson Liu, MD         
Sub-Investigator: Jeffrey M Lipton, MD, PhD         
Sponsors and Collaborators
Northwell Health
Investigators
Principal Investigator: Adrianna Vlachos, MD Northwell Health/Feinstein Institute for Medical Research
Principal Investigator: Johnson Liu, MD Northwell Health/Feinstein Institute for Medical Research
  More Information

Publications:

Responsible Party: Adrianna Vlachos, Principal Investigator, Northwell Health
ClinicalTrials.gov Identifier: NCT01464164     History of Changes
Other Study ID Numbers: 11-02-199 - 06A 
Study First Received: October 31, 2011
Last Updated: June 15, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Northwell Health:
Diamond Blackfan anemia
Blackfan Diamond anemia
Congenital pure red cell aplasia
Congenital Hypoplastic Anemia
Erythrogenesis Imperfecta
Hypoplastic Congenital Anemia
Inherited Erythroblastopenia
DBA
Aase-Smith II Syndrome
Aase Syndrome
Anemia, Congenital Pure Red Cell
Aplasia, Congenital Pure Red Cell
BDA
pure red cell aplasia
bone marrow failure syndrome

Additional relevant MeSH terms:
Anemia
Anemia, Diamond-Blackfan
Hematologic Diseases
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Red-Cell Aplasia, Pure
Bone Marrow Diseases
Genetic Diseases, Inborn
Prednisone
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 30, 2016