Safety and Efficacy Study of Sotatercept in Adults With Transfusion Dependent Diamond Blackfan Anemia (ACE-011-DBA)
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.
|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|
- 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
- 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)
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||February 2013 (Final data collection date for primary outcome measure)|
Sotatercept to be given as a subcutaneous injection once a month for 4 consecutive months, using a dose escalation scale among 3 cohorts.
Dose escalation study of the drug sotatercept to be given as a subcutaneous injection:
Cohorts of 3 subjects will receive sotatercept every 28 days for up to 4 doses. Starting dose of 0.1 mg/kg (dose level 1). The second and subsequent cohorts may begin after and only after all 3 subjects in the first cohort have completed 28 days following their 4th dose of sotatercept (or last dose if sotatercept is not discontinued for safety reasons) and safety has been determined to proceed. Subsequent dose levels are 0.3 mg/kg (dose level 2) and 0.5 mg/kg (dose level 3).
Other Name: ACE-011
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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.
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.
|Contact: Ellen Muir, MSN, RN, CNSemail@example.com|
|Contact: Eva Atsidaftos, MAfirstname.lastname@example.org|
|United States, New York|
|North Shore- LIJ campus of The Feinstein Institute for Medical Research||Recruiting|
|Manhasset, New York, United States, 11030|
|Contact: Ellen Muir, MSN, RN, CNS 516-562-1505 email@example.com|
|Contact: Eva Atsidaftos, MA 516-562-1504 firstname.lastname@example.org|
|Principal Investigator: Adrianna Vlachos, MD|
|Principal Investigator: Johnson Liu, MD|
|Sub-Investigator: Jeffrey M Lipton, MD, PhD|
|Principal Investigator:||Adrianna Vlachos, MD||North Shore- Long Island Jewish Medical Center; Cohen Children's Medical Center of NY|
|Principal Investigator:||Johnson Liu, MD||North Shore- Long Island Jewish Medical Center|