Immune Thrombocytopenia
Conditions
Keywords
ITP
Brief summary
A Phase 3b Study to Evaluate the Efficacy and Safety of Avatrombopag for the Treatment of Thrombocytopenia in Pediatric Subjects with Immune Thrombocytopenia for ≥6 Months
Detailed description
Subjects will be randomized in to blinded therapy of avatrombopag or placebo in a 3:1 ratio for a period of 12 weeks. Subjects who complete the 12 week treatment period and are eligible may continue to the open label extension phase which will last 2 years.
Interventions
DRUGAvatrombopag
Oral avatrombopag tablet or sprinkle capsule
DRUGPlacebo
Placebo comparator tablet or sprinkle capsule
Sponsors
Sobi, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
1 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male or female participants ≥1 and \<18 years of age at Screening and Baseline with a diagnosis of primary ITP for ≥6 months duration and has had an insufficient response to a previous treatment, in the opinion of the Investigator. * Participant has an average of 2 platelet counts \<30×10\^9/L with no single count \>35×10\^9/L in the screening period
Exclusion criteria
* Participants must not have a known history of secondary ITP, any history of arterial or venous thrombosis, including partial or complete thrombosis, known inherited thrombocytopenia, a history of myelodysplastic syndrome (MDS) or known history of congenital heart abnormalities or arrhythmias.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Durable Platelet Response | Last 8 weeks of 12 week treatment regimen | The proportion of subjects achieving at least 6 out of 8 weekly platelet counts ≥50×10\^9/L during the last 8 weeks of the 12 week Treatment Period in the Core Phase, in the absence of rescue medication |
| Alternative Primary: Platelet Response | 12 weeks of treatment | The proportion of subjects for whom at least 2 consecutive platelet assessments are ≥50×10\^9/L over the 12 weeks of treatment in the Core Phase in the absence of rescue medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Weeks Platelet Count ≥50×10^9/L | 12 weeks of treatment | The percentage of weeks subjects have a platelet count ≥50×10\^9/L during 12 weeks of treatment in the Core Phase, in the absence of rescue therapy. |
| Platelet Response at Day 8 | Day 8 | The proportion of subjects with a platelet count ≥50×10\^9/L at day 8, in the absence of rescue therapy. |
| Percentage of Weeks Platelet Count Between ≥50×10^9/L and ≤150×10^9/L | 12 weeks of treatment | The percentage of weeks subjects have a platelet count between ≥50×10\^9/L and ≤150×10\^9/L, during 12 weeks of treatment in the Core Phase, in the absence of rescue therapy. |
| Rescue Medications | 12 weeks of treatment | The proportion of subjects who require rescue medications during 12 weeks of treatment in the Core Phase of the study. |
| Incidence of Any Bleeding Event (WHO Grade 1-4) | 12 weeks of treatment | Overall incidence of bleeding events associated with ITP measured using the WHO Bleeding Scale (Grade 1-4). |
Countries
France, Germany, Hungary, Poland, Russia, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
Open label extension optional and not all subjects entered this phase. 73 of 75 subjects entered this phase; 2 dropped out after the core phase.
Participants by arm
| Arm | Count |
|---|---|
| Experimental: Avatrombopag Study is 3:1 randomization ratio (avatrombopag to placebo). Investigational product administered orally once daily for 12 weeks
Avatrombopag: Oral avatrombopag tablet or sprinkle capsule | 54 |
| Placebo Comparator:Placebo Study is 3:1 randomization ratio (avatrombopag to placebo). Investigational product administered orally once daily for 12 weeks
Placebo: Placebo comparator tablet or sprinkle capsule | 21 |
| Total | 75 |
Baseline characteristics
| Characteristic | Experimental: Avatrombopag | Total | Placebo Comparator:Placebo |
|---|---|---|---|
| Age, Continuous | 8.9 years STANDARD_DEVIATION 4.36 | 9.2 years STANDARD_DEVIATION 4.29 | 9.9 years STANDARD_DEVIATION 4.13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants | 65 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 8 Participants | 5 Participants |
| Race (NIH/OMB) White | 48 Participants | 63 Participants | 15 Participants |
| Region of Enrollment France | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Germany | 2 participants | 3 participants | 1 participants |
| Region of Enrollment Hungary | 4 participants | 5 participants | 1 participants |
| Region of Enrollment Poland | 3 participants | 4 participants | 1 participants |
| Region of Enrollment Russia | 4 participants | 5 participants | 1 participants |
| Region of Enrollment Turkey | 20 participants | 29 participants | 9 participants |
| Region of Enrollment Ukraine | 2 participants | 2 participants | 0 participants |
| Region of Enrollment United Kingdom | 11 participants | 13 participants | 2 participants |
| Region of Enrollment United States | 8 participants | 13 participants | 5 participants |
| Sex: Female, Male Female | 24 Participants | 36 Participants | 12 Participants |
| Sex: Female, Male Male | 30 Participants | 39 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 54 | 0 / 21 | 0 / 73 |
| other Total, other adverse events | 50 / 54 | 16 / 21 | 71 / 73 |
| serious Total, serious adverse events | 5 / 54 | 1 / 21 | 22 / 73 |
Outcome results
Primary
Alternative Primary: Platelet Response
The proportion of subjects for whom at least 2 consecutive platelet assessments are ≥50×10\^9/L over the 12 weeks of treatment in the Core Phase in the absence of rescue medication.
Time frame: 12 weeks of treatment
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Avatrombopag | Alternative Primary: Platelet Response | 44 Participants |
| Placebo Comparator:Placebo | Alternative Primary: Platelet Response | 0 Participants |
p-value: <0.0001Fisher Exact
Primary
Durable Platelet Response
The proportion of subjects achieving at least 6 out of 8 weekly platelet counts ≥50×10\^9/L during the last 8 weeks of the 12 week Treatment Period in the Core Phase, in the absence of rescue medication
Time frame: Last 8 weeks of 12 week treatment regimen
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Avatrombopag | Durable Platelet Response | 15 Participants |
| Placebo Comparator:Placebo | Durable Platelet Response | 0 Participants |
p-value: 0.0077Fisher Exact
Secondary
Incidence of Any Bleeding Event (WHO Grade 1-4)
Overall incidence of bleeding events associated with ITP measured using the WHO Bleeding Scale (Grade 1-4).
Time frame: 12 weeks of treatment
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Avatrombopag | Incidence of Any Bleeding Event (WHO Grade 1-4) | 45 Participants |
| Placebo Comparator:Placebo | Incidence of Any Bleeding Event (WHO Grade 1-4) | 19 Participants |
p-value: 0.7175Fisher Exact
Secondary
Percentage of Weeks Platelet Count ≥50×10^9/L
The percentage of weeks subjects have a platelet count ≥50×10\^9/L during 12 weeks of treatment in the Core Phase, in the absence of rescue therapy.
Time frame: 12 weeks of treatment
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Avatrombopag | Percentage of Weeks Platelet Count ≥50×10^9/L | 48.9 percentage of weeks | Standard Deviation 25.22 |
| Placebo Comparator:Placebo | Percentage of Weeks Platelet Count ≥50×10^9/L | 1.2 percentage of weeks | Standard Deviation 3.92 |
p-value: <0.0001t-test, 2 sided
Secondary
Percentage of Weeks Platelet Count Between ≥50×10^9/L and ≤150×10^9/L
The percentage of weeks subjects have a platelet count between ≥50×10\^9/L and ≤150×10\^9/L, during 12 weeks of treatment in the Core Phase, in the absence of rescue therapy.
Time frame: 12 weeks of treatment
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Avatrombopag | Percentage of Weeks Platelet Count Between ≥50×10^9/L and ≤150×10^9/L | 29.2 percentage of weeks | Standard Deviation 19.64 |
| Placebo Comparator:Placebo | Percentage of Weeks Platelet Count Between ≥50×10^9/L and ≤150×10^9/L | 1.2 percentage of weeks | Standard Deviation 3.92 |
p-value: <0.0001t-test, 2 sided
Secondary
Platelet Response at Day 8
The proportion of subjects with a platelet count ≥50×10\^9/L at day 8, in the absence of rescue therapy.
Time frame: Day 8
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Avatrombopag | Platelet Response at Day 8 | 30 Participants |
| Placebo Comparator:Placebo | Platelet Response at Day 8 | 0 Participants |
p-value: <0.0001Fisher Exact
Secondary
Rescue Medications
The proportion of subjects who require rescue medications during 12 weeks of treatment in the Core Phase of the study.
Time frame: 12 weeks of treatment
Population: Full Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental: Avatrombopag | Rescue Medications | 4 Participants |
| Placebo Comparator:Placebo | Rescue Medications | 9 Participants |
p-value: 0.0008Fisher Exact