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Trial record 5 of 21 for:    sotatercept

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

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ClinicalTrials.gov Identifier: NCT01464164
Recruitment Status : Terminated (Supporter terminated the study due to no active patients (secondary to travel restrictions due to COVID).)
First Posted : November 3, 2011
Results First Posted : December 21, 2021
Last Update Posted : December 21, 2021
Sponsor:
Information provided by (Responsible Party):
Adrianna Vlachos, Northwell Health

Tracking Information
First Submitted Date  ICMJE October 31, 2011
First Posted Date  ICMJE November 3, 2011
Results First Submitted Date  ICMJE October 12, 2021
Results First Posted Date  ICMJE December 21, 2021
Last Update Posted Date December 21, 2021
Actual Study Start Date  ICMJE January 2012
Actual Primary Completion Date April 13, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 22, 2021)
Number of Participants With Complete Response and Partial Response [ Time Frame: 9 months ]
Complete response is transfusion independence with hemoglobin >9 gm/dl; partial response is transfusion dependence with hemoglobin < 9gm/dl with an increase in reticulocyte count over baseline
Original Primary Outcome Measures  ICMJE
 (submitted: November 2, 2011)
Determine a safe and effective dose of sotatercept in adults with DBA and RBC transfusion dependence [ Time Frame: 9 months ]
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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 22, 2021)
Severe Adverse Events Attributable to Study Drug [ Time Frame: 9 months ]
Assess 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
Original Secondary Outcome Measures  ICMJE
 (submitted: November 2, 2011)
  • Safety [ Time Frame: 9 months ]
    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 ]
    Length of time required to achieve a response
  • Response duration [ Time Frame: 9 months ]
    Length of time between transfusions
  • Exploratory outcome improvement of bone density [ Time Frame: 9 months ]
    Improvement as measured by bone densitometry (DEXA scan)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of Sotatercept in Adults With Transfusion Dependent Diamond Blackfan Anemia
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description

This study is for adult patients with Diamond Blackfan Anemia who are currently being transfused every 3- 4 weeks.

The drug will be given as a subcutaneous injection within one of three dose levels. The first dose level (0.1 mg/kg) will include 3 subjects who will receive the same dose of the drug monthly for a total of 4 doses, as long as there are no dose- limiting toxicities (DLTs). A Dose limiting toxicity is defined as inability to deliver the scheduled doses because of toxicity >/= Grade 3, according to NCI Toxicity Grading Scale.

Once all 3 subjects have received and tolerated the low dose level, the next level will open (0.3 mg/kg)to 3 new subjects. Subjects will be monitored closely for response and side effects.

If more than 2 subjects have a dose limiting toxicity in the first dose level, then dose level -1 (0.05 mg/kg)will open, enrolling 3 more subjects. If more than 2 subjects at dose level -1, have dose limiting toxicities, the study will be discontinued. If there are no additional dose limiting toxicities, dose level -1 will be the maximum tolerated dose.

There are a total of 3 dose levels, not including dose level -1. Once the maximum tolerated dose has been reached, up to a total of 10 additional subjects will be enrolled.

Protocol Amendment: The protocol has been amended to include an additional enrollment of 20 subjects with two additional dose levels of Sotatercept (0.075 mg/kg and 0.100 mg/kg ) to be given with or without a prednisone boost.

Efficacy will be measured by response. A complete response will be determined if the subject no longer requires transfusion, while on study drug. A partial response will be measured by a reduction by 50% in need for transfusion.

Treatment modifications will be made based on evidence of side effects. Dose- escalation will be performed only if no side effects are reported and no efficacy is evidenced. Treatment will be stopped if hemoglobin is >12 gm/dl and/ or any >/+ grade 3 adverse event is related to sotatercept.

Study assessments will include:

  • Physical exam (height, weight, vital signs and blood pressure)at screening, day 1 of each cycle and monthly for 3 months of follow up period as well as at study discontinuation.
  • Additional blood pressure monitoring at day 1 of each cycle and weekly there after through cycle 4, monthly in follow up period and at study discontinuation.
  • Karnofsky performance status at screening, day 1 of cycle 2 and day 1 of monthly follow up period for 3 months and study discontinuation.
  • CBC reticulocyte count and ANC will be collected at day 1 of each cycle and weekly there after through cycle 4, monthly in follow up period and at study discontinuation.
  • Blood chemistry, liver and kidney function will be assessed at screening, day 1 and 15 of cycle 1, day 1 of cycle 2, 3, 4 month 1 in follow up and at study discontinuation.
  • Blood for iron status (serum iron, transferrin and %, ferritin) will be collected during the screening period, and at month 1 of the follow-up period as well as study discontinuation.
  • Folate and B12 levels will be assessed during the screening period at day 1 of cycle 3 and again at study discontinuation.
  • Urinalysis (creatinine, protein),at screening, day 15 of cycle 1, day 1 of cycles 2, 3, and 4 monthly during follow-up and at study discontinuation.
  • Serum erythropoietin at screening, day 15 of cycle 1, day 1 of cycle 3, monthly during follow-up and at study discontinuation.
  • FSH & LH (everyone), DHEA & testosterone (males only), estrogen & estradiol (females only)at screening, day 1 of cycles 2, 3, and 4, monthly during follow- up period and at study discontinuation.
  • EKG & ECHO at screening, day 1 of cycle 3 first month of follow-up period and at study discontinuation
  • Dexa Scan at screening, day 1 of monthly follow-up period and at study discontinuation
  • Transfusion assessment at screening, day 1, 8, 15 and 22 of cycle 1, day 1 and 15 of cycles 2, 3, and 4, monthly during follow-up period and at study discontinuation.
  • Response assessment at day 8, 15, 22 of cycle 1, day 1 and 15 of cycles2, 3, and 4, monthly for 3 months during follow-up period and at study discontinuation
  • Adverse events, concomitant therapies to be assessed at day 1, 8, 15, and 22 of cycle 1, day 1 and 15 of cycles 2, 3, and 4, monthly during follow-up period and at study discontinuation
  • Drug administration day 1 of cycles 1, 2, 3, and 4.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Diamond Blackfan Anemia
Intervention  ICMJE
  • Drug: Sotatercept

    Cohort 4a: 3 patients on Sotatercept 0.75 mg/kg every 3 weeks. 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 every 3 weeks

    Other Name: ACE-011
  • Drug: Sotatercept with prednisone boost

    Cohort 4b: 3 patients on Sotatercept 0.75 mg/kg every 3 weeks with a three week prednisone boost of 1 mg/kg/day (max 60 mg). 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 every 3 weeks with a 3 week prednisone boost of 1 mg/kg/day (max 60 mg).

    Other Name: ACE-011 and Prednisone
Study Arms  ICMJE
  • Experimental: 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 0.75mg/kg and 1 mg/kg as a subcutaneous injection once every 3 weeks.
    Intervention: Drug: Sotatercept
  • Experimental: Sotatercept with prednisone boost
    Protocol Amendment: Two additional cohorts will be given Sotatercept 0.75mg/kg and 1 mg/kg as a subcutaneous injection once every 3 weeks along with a prednisone boost of 1 mg/kg daily for 3 weeks (max of 60 mg).
    Intervention: Drug: Sotatercept with prednisone boost
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 22, 2021)
19
Original Estimated Enrollment  ICMJE
 (submitted: November 2, 2011)
20
Actual Study Completion Date  ICMJE April 13, 2021
Actual Primary Completion Date April 13, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01464164
Other Study ID Numbers  ICMJE 11-02-199 - 06A
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Adrianna Vlachos, Northwell Health
Study Sponsor  ICMJE Northwell Health
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Adrianna Vlachos, MD Northwell Health/Feinstein Institute for Medical Research
PRS Account Northwell Health
Verification Date November 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP