Safety and Efficacy Study of Sotatercept in Adults With Transfusion Dependent Diamond Blackfan Anemia
- Conditions
- Diamond Blackfan Anemia
- Interventions
- Registration Number
- NCT01464164
- Lead Sponsor
- Northwell Health
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 19
- >/= 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sotatercept 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. Sotatercept with prednisone boost 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).
- Primary Outcome Measures
Name Time Method Number of Participants With Complete Response and Partial Response 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
- Secondary Outcome Measures
Name Time Method Severe Adverse Events Attributable to Study Drug 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
Trial Locations
- Locations (1)
North Shore- LIJ campus of The Feinstein Institute for Medical Research
🇺🇸Manhasset, New York, United States