Safety and Efficacy Study of Sotatercept in Adults With Transfusion Dependent Diamond Blackfan Anemia
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Anemia |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 3/15/2019 |
| Start Date: | January 2012 |
| End Date: | May 2020 |
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
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.
subcutaneous injection, to stimulate production of red blood cell production. To be given
every 28 days for up to four doses.
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.
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.
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
We found this trial at
1
site
Manhasset, New York 11030
Principal Investigator: Adrianna Vlachos, MD
Phone: 516-562-1504
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