Trial Outcomes & Findings for Treatment of Refractory Diamond-Blackfan Anemia With Eltrombopag (NCT NCT04269889)
NCT ID: NCT04269889
Last Updated: 2025-04-27
Results Overview
Participants that responded to Eltrombopag as defined by: Response to treatment will be defined by one or more of the following: * Erythroid response for subjects with a pretreatment hemoglobin less than 9 G/dL will be defined as an increase in hemoglobin by \>1.5 G/dL from enrollment baseline, and/or * A reduction in the units of PRBC transfusions by at least 50% during the eight consecutive weeks prior to response assessment - compared with the pretreatment transfusion number in the previous 8 weeks.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
15 participants
Primary outcome timeframe
6 months (24 weeks +/- 14 days)
Results posted on
2025-04-27
Participant Flow
Participants were recruited and enrolled from February 2020 through August 2022 at the National Institutes of Health (NIH) (Bethesda, MD).
Participant milestones
| Measure |
Refractory Diamond-Blackfan Anemia in Eltrombopag
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
|---|---|
|
Initial Phase (Day 0 to Month 6)
STARTED
|
15
|
|
Initial Phase (Day 0 to Month 6)
COMPLETED
|
1
|
|
Initial Phase (Day 0 to Month 6)
NOT COMPLETED
|
14
|
|
Extended Phase (6 Months to Year 3)
STARTED
|
1
|
|
Extended Phase (6 Months to Year 3)
COMPLETED
|
1
|
|
Extended Phase (6 Months to Year 3)
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Refractory Diamond-Blackfan Anemia in Eltrombopag
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
|---|---|
|
Initial Phase (Day 0 to Month 6)
Lack of Efficacy
|
14
|
Baseline Characteristics
Treatment of Refractory Diamond-Blackfan Anemia With Eltrombopag
Baseline characteristics by cohort
| Measure |
Refractory Diamond-Blackfan Anemia in Eltrombopag
n=15 Participants
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
|---|---|
|
Age, Categorical
<=18 years
|
7 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
14 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
15 participants
n=5 Participants
|
|
Number of participants with Iron Overload
|
14 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 months (24 weeks +/- 14 days)Participants that responded to Eltrombopag as defined by: Response to treatment will be defined by one or more of the following: * Erythroid response for subjects with a pretreatment hemoglobin less than 9 G/dL will be defined as an increase in hemoglobin by \>1.5 G/dL from enrollment baseline, and/or * A reduction in the units of PRBC transfusions by at least 50% during the eight consecutive weeks prior to response assessment - compared with the pretreatment transfusion number in the previous 8 weeks.
Outcome measures
| Measure |
Refractory Diamond-Blackfan Anemia in Eltrombopag
n=15 Participants
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 3 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 4 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
|---|---|---|---|
|
Participants That Responded to Eltrombopag
Response to Treatment
|
1 Participants
|
—
|
—
|
|
Participants That Responded to Eltrombopag
No Response to Treatment
|
14 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: 6 months (24 weeks +/- 14 days)Population: Analysis includes only participants that responded to eltrombopag
Time-to-response in weeks will also be measured according to the time from Eltrombopag initiation to the first time the patient met criteria for response. Response to treatment will be defined by one or more of the following: * Erythroid response for subjects with a pretreatment hemoglobin less than 9 G/dL will be defined as an increase in hemoglobin by \>1.5 G/dL from enrollment baseline, and/or * a reduction in the units of PRBC transfusions by at least 50% during the eight consecutive weeks prior to response assessment - compared with the pretreatment transfusion number in the previous 8 weeks.
Outcome measures
| Measure |
Refractory Diamond-Blackfan Anemia in Eltrombopag
n=1 Participants
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 3 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 4 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
|---|---|---|---|
|
Time (Weeks) to Response
|
15 weeks
|
—
|
—
|
PRIMARY outcome
Timeframe: 6 months (24 weeks +/- 14 days)Population: Analysis includes number of adverse events with grade 2 events and above
Number of Adverse Events Toxicity profile as measured by using the Common Terminology Criteria for Adverse Events (CTCAE version 5.0) for grade 2 and above. According to https://ctep.cancer.gov/, CTCAE is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. CTCAE grades are defined as: Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated.
Outcome measures
| Measure |
Refractory Diamond-Blackfan Anemia in Eltrombopag
n=15 Participants
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 3 Adverse Events
n=15 Participants
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 4 Adverse Events
n=15 Participants
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
|---|---|---|---|
|
Number of Adverse Events
Headache
|
0 Adverse Events
|
2 Adverse Events
|
0 Adverse Events
|
|
Number of Adverse Events
Arthralgia
|
1 Adverse Events
|
1 Adverse Events
|
0 Adverse Events
|
|
Number of Adverse Events
Back pain
|
1 Adverse Events
|
0 Adverse Events
|
0 Adverse Events
|
|
Number of Adverse Events
Chills
|
1 Adverse Events
|
1 Adverse Events
|
0 Adverse Events
|
|
Number of Adverse Events
Dysphagia
|
1 Adverse Events
|
0 Adverse Events
|
0 Adverse Events
|
|
Number of Adverse Events
Fever
|
1 Adverse Events
|
1 Adverse Events
|
0 Adverse Events
|
|
Number of Adverse Events
Flu-like symptoms: COVID/flu
|
0 Adverse Events
|
1 Adverse Events
|
0 Adverse Events
|
|
Number of Adverse Events
Elevated alanine transaminase
|
0 Adverse Events
|
1 Adverse Events
|
0 Adverse Events
|
|
Number of Adverse Events
Acute inception without sepsis/Acute viral syndrome
|
1 Adverse Events
|
0 Adverse Events
|
0 Adverse Events
|
|
Number of Adverse Events
Myalgia
|
1 Adverse Events
|
0 Adverse Events
|
0 Adverse Events
|
|
Number of Adverse Events
Nausea
|
0 Adverse Events
|
1 Adverse Events
|
0 Adverse Events
|
|
Number of Adverse Events
Sepsis
|
0 Adverse Events
|
1 Adverse Events
|
0 Adverse Events
|
SECONDARY outcome
Timeframe: 3 MonthsNumber of Participants That Responded to Eltrombopag. As determined by the response to treatment, which will be assessed based on one or more of the following criteria: Erythroid response for subjects with a pretreatment hemoglobin less than 9 G/dL will be defined as an increase in hemoglobin by \>1.5 G/dL from enrollment baseline, and/or A reduction in the units of PRBC transfusions by at least 50% during the eight consecutive weeks prior to response assessment - compared with the pretreatment transfusion number in the previous 8 weeks.
Outcome measures
| Measure |
Refractory Diamond-Blackfan Anemia in Eltrombopag
n=15 Participants
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 3 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 4 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
|---|---|---|---|
|
Number of Participants That Responded to Eltrombopag
Response to Treatment
|
0 Participants
|
—
|
—
|
|
Number of Participants That Responded to Eltrombopag
No Response to Treatment
|
15 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 3 Months, 6 Months, Up to 27 MonthsPopulation: Analysis post 6 months only includes those participants that met criteria for extension phase of the study
Number of Participants with Robust Response to Eltrombopag regardless when it is achieved. Best response is defined as robust response or not robust response. Robust response to treatment will be defined both: * Stable hemoglobin (two consecutive measurements at least 2 weeks apart) greater than 10 g/dL, and * Transfusion independence for the previous 8 weeks
Outcome measures
| Measure |
Refractory Diamond-Blackfan Anemia in Eltrombopag
n=15 Participants
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 3 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 4 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
|---|---|---|---|
|
Number of Participants With Robust Response to Eltrombopag
3 months : Robust Response
|
0 Participants
|
—
|
—
|
|
Number of Participants With Robust Response to Eltrombopag
3 months : Not Robust Response
|
15 Participants
|
—
|
—
|
|
Number of Participants With Robust Response to Eltrombopag
6 months : Robust Response
|
0 Participants
|
—
|
—
|
|
Number of Participants With Robust Response to Eltrombopag
6 months : Not Robust Response
|
15 Participants
|
—
|
—
|
|
Number of Participants With Robust Response to Eltrombopag
Up to 27 months : Robust Response
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 3 monthsPopulation: Analysis includes those participants that completed baseline and month 3 visits
Median Change in Platelet Count as measured by serial CBC assessments
Outcome measures
| Measure |
Refractory Diamond-Blackfan Anemia in Eltrombopag
n=12 Participants
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 3 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 4 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
|---|---|---|---|
|
Median Change in Platelet Count
|
83.0 K/uL
Interval -10.0 to 432.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Month 3Population: Analysis includes those participants that completed baseline and month 3 visits
Median Change Absolute Neutrophil Count as measured by serial CBC assessments
Outcome measures
| Measure |
Refractory Diamond-Blackfan Anemia in Eltrombopag
n=12 Participants
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 3 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 4 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
|---|---|---|---|
|
Median Change Absolute Neutrophil Count
|
0.7 K/uL
Interval -2.6 to 4.2
|
—
|
—
|
SECONDARY outcome
Timeframe: 6 months up to 27 monthsPopulation: All participants that participated within the extended phase of the clinical trial
Number of Participants that experienced Relapse during extension phase. Relapse is defined as no longer meeting response criteria. Response criteria is defined as: Response to treatment will be defined by one or more of the following: * Erythroid response for subjects with a pretreatment hemoglobin less than 9 G/dL will be defined as an increase in hemoglobin by \>1.5 G/dL from enrollment baseline, and/or * A reduction in the units of PRBC transfusions by at least 50% during the eight consecutive weeks prior to response assessment - compared with the pretreatment transfusion number in the previous 8 weeks.
Outcome measures
| Measure |
Refractory Diamond-Blackfan Anemia in Eltrombopag
n=1 Participants
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 3 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 4 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
|---|---|---|---|
|
Number of Participants That Experienced Relapse
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 6 Months and Up to 27 monthsPopulation: Analysis post 6 months only includes those participants that met criteria for extension phase of the study
Number of participants that experienced clonal evolution according to cytogenetic, mutational or flow cytometric markers
Outcome measures
| Measure |
Refractory Diamond-Blackfan Anemia in Eltrombopag
n=15 Participants
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 3 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 4 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
|---|---|---|---|
|
Number of Participants That Experienced Clonal Evolution
6 months
|
0 Participants
|
—
|
—
|
|
Number of Participants That Experienced Clonal Evolution
Up to 27 months
|
1 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 6 months Up to 27 monthsPopulation: All participants that participated within the extended phase of the clinical trial
Number of Adverse Events Toxicity profile as measured by using the Common Terminology Criteria for Adverse Events (CTCAE version 5.0) for grade 2 and above. According to https://ctep.cancer.gov/, CTCAE is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. CTCAE grades are defined as: Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated.
Outcome measures
| Measure |
Refractory Diamond-Blackfan Anemia in Eltrombopag
n=1 Participants
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 3 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 4 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
|---|---|---|---|
|
Number of Adverse Events During the Extension Phase
Grade 3
|
0 Adverse Events
|
—
|
—
|
|
Number of Adverse Events During the Extension Phase
Grade 2
|
0 Adverse Events
|
—
|
—
|
|
Number of Adverse Events During the Extension Phase
Grade 4
|
0 Adverse Events
|
—
|
—
|
|
Number of Adverse Events During the Extension Phase
Grade 5
|
0 Adverse Events
|
—
|
—
|
SECONDARY outcome
Timeframe: At baseline and Month 6Population: Data was not collected and there are no future plans to collect the data. The analysis could not be completed due to insufficient staffing to carry out the required tasks.
Neurodevelopment in pediatric patients as measured by validated neurodevelopmental measurements
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Month 6Number of participants with Iron overload. Iron overload as measured by serial ferritin levels, T2\* MRI measurements and bone marrow iron staining
Outcome measures
| Measure |
Refractory Diamond-Blackfan Anemia in Eltrombopag
n=15 Participants
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 3 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
Refractory Diamond-Blackfan Anemia in Eltrombopag With Grade 4 Adverse Events
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
|---|---|---|---|
|
Number of Participants With Iron Overload
|
15 Participants
|
—
|
—
|
Adverse Events
Refractory Diamond-Blackfan Anemia in Eltrombopag
Serious events: 2 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Refractory Diamond-Blackfan Anemia in Eltrombopag
n=15 participants at risk
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
|---|---|
|
Gastrointestinal disorders
Nausea
|
6.7%
1/15 • Number of events 1 • up to 27 months
Grade 2 adverse events and above, including clinically significant abnormal non-hematologic findings on laboratory evaluations, regardless of severity and attribution, will be recorded at each study visit and followed until satisfactory resolution.
|
|
General disorders
Chills
|
6.7%
1/15 • Number of events 1 • up to 27 months
Grade 2 adverse events and above, including clinically significant abnormal non-hematologic findings on laboratory evaluations, regardless of severity and attribution, will be recorded at each study visit and followed until satisfactory resolution.
|
|
General disorders
Fever
|
6.7%
1/15 • Number of events 1 • up to 27 months
Grade 2 adverse events and above, including clinically significant abnormal non-hematologic findings on laboratory evaluations, regardless of severity and attribution, will be recorded at each study visit and followed until satisfactory resolution.
|
|
Hepatobiliary disorders
Elevated alanine transaminase
|
6.7%
1/15 • Number of events 1 • up to 27 months
Grade 2 adverse events and above, including clinically significant abnormal non-hematologic findings on laboratory evaluations, regardless of severity and attribution, will be recorded at each study visit and followed until satisfactory resolution.
|
|
Infections and infestations
Flu like symptoms
|
6.7%
1/15 • Number of events 1 • up to 27 months
Grade 2 adverse events and above, including clinically significant abnormal non-hematologic findings on laboratory evaluations, regardless of severity and attribution, will be recorded at each study visit and followed until satisfactory resolution.
|
|
Infections and infestations
Sepsis
|
6.7%
1/15 • Number of events 1 • up to 27 months
Grade 2 adverse events and above, including clinically significant abnormal non-hematologic findings on laboratory evaluations, regardless of severity and attribution, will be recorded at each study visit and followed until satisfactory resolution.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.7%
1/15 • Number of events 1 • up to 27 months
Grade 2 adverse events and above, including clinically significant abnormal non-hematologic findings on laboratory evaluations, regardless of severity and attribution, will be recorded at each study visit and followed until satisfactory resolution.
|
|
Nervous system disorders
Headache
|
6.7%
1/15 • Number of events 1 • up to 27 months
Grade 2 adverse events and above, including clinically significant abnormal non-hematologic findings on laboratory evaluations, regardless of severity and attribution, will be recorded at each study visit and followed until satisfactory resolution.
|
Other adverse events
| Measure |
Refractory Diamond-Blackfan Anemia in Eltrombopag
n=15 participants at risk
Participants with Refractory Diamond-Blackfan Anemia will be administered Eltrombopag. Participants 12 years of age an above will receive the adult dose of 150 mg by mouth daily. Participants between ages of 6 and 11 years old will start at 75 mg by mouth daily, and children 2 and 5 years of age will start at 2.5 mg/kg, not to exceed 75 mg by mouth daily.
To adjust for the higher expected exposure in participants of East Asian and South East Asian ancestry, the starting dose for East Asian and South East Asian participants 12 years of age and above will be 75 mg by mouth once daily. For East Asian and South East Asian participants between 6 and 11 years of age, the starting dose will be 37.5 mg once daily by mouth, and for children between 2 and 5, the starting dose will be 1.25 mg/kg by mouth.
|
|---|---|
|
Gastrointestinal disorders
Dysphagia
|
6.7%
1/15 • Number of events 1 • up to 27 months
Grade 2 adverse events and above, including clinically significant abnormal non-hematologic findings on laboratory evaluations, regardless of severity and attribution, will be recorded at each study visit and followed until satisfactory resolution.
|
|
General disorders
Fever
|
6.7%
1/15 • Number of events 1 • up to 27 months
Grade 2 adverse events and above, including clinically significant abnormal non-hematologic findings on laboratory evaluations, regardless of severity and attribution, will be recorded at each study visit and followed until satisfactory resolution.
|
|
Infections and infestations
Acute inception without sepsis/Acute viral syndrome
|
6.7%
1/15 • Number of events 1 • up to 27 months
Grade 2 adverse events and above, including clinically significant abnormal non-hematologic findings on laboratory evaluations, regardless of severity and attribution, will be recorded at each study visit and followed until satisfactory resolution.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.7%
1/15 • Number of events 1 • up to 27 months
Grade 2 adverse events and above, including clinically significant abnormal non-hematologic findings on laboratory evaluations, regardless of severity and attribution, will be recorded at each study visit and followed until satisfactory resolution.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.7%
1/15 • Number of events 1 • up to 27 months
Grade 2 adverse events and above, including clinically significant abnormal non-hematologic findings on laboratory evaluations, regardless of severity and attribution, will be recorded at each study visit and followed until satisfactory resolution.
|
|
Musculoskeletal and connective tissue disorders
Chills
|
6.7%
1/15 • Number of events 1 • up to 27 months
Grade 2 adverse events and above, including clinically significant abnormal non-hematologic findings on laboratory evaluations, regardless of severity and attribution, will be recorded at each study visit and followed until satisfactory resolution.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.7%
1/15 • Number of events 1 • up to 27 months
Grade 2 adverse events and above, including clinically significant abnormal non-hematologic findings on laboratory evaluations, regardless of severity and attribution, will be recorded at each study visit and followed until satisfactory resolution.
|
|
Nervous system disorders
Headache
|
6.7%
1/15 • Number of events 1 • up to 27 months
Grade 2 adverse events and above, including clinically significant abnormal non-hematologic findings on laboratory evaluations, regardless of severity and attribution, will be recorded at each study visit and followed until satisfactory resolution.
|
Additional Information
David J. Young, MD, PhD
National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH)
Phone: 301.827.7823
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place