Idiopathic Thrombocytopenic Purpura, Thrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP), Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
Conditions
Keywords
Immune (Idiopathic) Thrombocytopenic Purpura, Pediatric Idiopathic Thrombocytopenic Purpura
Brief summary
The purpose of this study is to evaluate the safety and tolerability of romiplostim (AMG 531) in the treatment of thrombocytopenia in pediatric subjects with chronic ITP. We will also evaluate the efficacy of romiplostim (AMG 531) and characterize the pharmacokinetics of romiplostim (AMG 531). It is anticipated that romiplostim (AMG 531), when given at an effective dose and schedule, will be well tolerated treatment for thrombocytopenia among pediatric subjects with chronic ITP.
Interventions
DRUGPlacebo
Starting dose of 1.0 ug/kg. Dose adjustments are made throughout the study based on individual platelet counts.
DRUGAMG 531
Starting dose of 1.0 ug/kg. Dose adjustments are made throughout the study based on individual platelet counts.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Before any study-specific procedure, the appropriate written informed consent must be obtained. In addition to the written informed consent, the assent of the child from those subjects capable of providing assent must also be obtained if requested by the IRB/IEC. * Diagnosis of ITP according to The American Society of Hematology (ASH) Guidelines at least six months prior to screening * Age ≥ 12 months and \< 18 years at enrollment * The mean of two platelet counts taken during the screening period must be ≤ 30 x 10\^9/L with no single count \>35 x 10\^9/L * A serum creatinine concentration ≤ 1.5 times the laboratory normal range (for each age category) * Adequate liver function; serum bilirubin ≤ 1.5 times the laboratory normal range * Hemoglobin \>10.0 g/dL
Exclusion criteria
* Known history of a bone marrow stem cell disorder (any abnormal bone marrow findings other than those typical of ITP must be approved by Amgen before a subject may be enrolled in the study) * Known history of venous or arterial thrombotic or thromboembolic event * Known history of congenital thrombocytopenia * Known history of malignancy except basal cell carcinoma * Known history of hepatitis B, hepatitis C, or HIV * Known history of systemic lupus erythematosus, Evans Syndrome, or autoimmune neutropenia * Known positive lupus anticoagulant or history of antiphospholipid antibody syndrome * Known history of Disseminated Intravascular Coagulation, Hemolytic Uremic Syndrome, or Thrombotic Thrombocytopenic Purpura * Currently receiving any treatment for ITP except for corticosteroids * IV Ig or anti-D Ig within two weeks prior to the screening visit * Rituximab (for any indication) within 14 weeks before the screening visit or anticipated use during the time of the proposed study * Splenectomy within eight weeks of the screening visit * Received hematopoietic growth factors including IL-11 (oprelvekin) within four weeks before the screening visit * Received any alkylating agents within eight weeks before the screening visit or anticipated use during the time of the proposed study * Subject is currently enrolled in or has not yet completed at least four weeks since ending other investigational device or drug trial(s), or subject is receiving investigational agent(s) * Past or present participation in any study evaluating PEG-rHuMGDF, recombinant human thrombopoietin (rHuTPO), AMG 531, or related platelet product * Pregnant (i.e. positive urine pregnancy test) or breast feeding * Subject is not using adequate contraceptive precautions, if applicable. * Known hypersensitivity to any recombinant E coli-derived product * Subject has any kind of disorder that compromises the ability to comply with all study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 12 weeks | Occurrence of one or more adverse events in the participant during the 12-week treatment period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weeks With Platelet Count ≥ 50 x 10^9/L | 12-week treatment period | The number of weeks with platelet count ≥ 50 x 10\^9/L during the 12 week treatment period. |
| Bleeding Events (Grade 2 or Higher) | 12-week treatment period (Weeks 2 - 13) | Total number of bleeding events (Grade 2 or higher, i.e., mild to life-threatening, as defined in the protocol) for each participant during Weeks 2-13 (end-of-study visit for non-responders) |
| Platelet Count ≥ 50 x 10^9/L for Two Consecutive Weeks | 12-week treatment period | Participant incidence of achieving a platelet count ≥50 x 10\^9/L for two consecutive weeks during the 12 week treatment period. |
| Increase in Platelet Count ≥ 20 x 10^9/L Above Baseline for Two Consecutive Weeks | 12-week treatment period | Participant incidence of achieving an increase in platelet count ≥20 x 10\^9/L above baseline for two consecutive weeks during the 12 week treatment period. |
| Requirement for Rescue Therapy (as Defined Per Protocol) | 12-week treatment period | Participant required rescue therapy (as defined per protocol) during the 12 week treatment period. |
Participant flow
Recruitment details
Participants were enrolled from 19 Jul 2007 through 11 November 2008
Participants by arm
| Arm | Count |
|---|---|
| Romiplostim Romiplostim by subcutaneous injection once weekly at a starting dose of 1 µg/kg, adjusted based on weekly platelet counts to a maximum weekly dose of 10 µg/kg | 17 |
| Placebo Placebo by subcutaneous injection once weekly | 5 |
| Total | 22 |
Baseline characteristics
| Characteristic | Romiplostim | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 9.4 Years STANDARD_DEVIATION 5.4 | 9.8 Years STANDARD_DEVIATION 4.6 | 9.5 Years STANDARD_DEVIATION 5.1 |
| Race/Ethnicity, Customized Black or African American | 5 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White or Caucasian | 9 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 13 Participants | 3 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 5 | 16 / 17 |
| serious Total, serious adverse events | 0 / 5 | 1 / 17 |
Outcome results
Primary
Adverse Events
Occurrence of one or more adverse events in the participant during the 12-week treatment period
Time frame: 12 weeks
Population: Safety Analysis Set, composed of all participants who received at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Romiplostim | Adverse Events | 16 Participants |
| Placebo | Adverse Events | 5 Participants |
Secondary
Bleeding Events (Grade 2 or Higher)
Total number of bleeding events (Grade 2 or higher, i.e., mild to life-threatening, as defined in the protocol) for each participant during Weeks 2-13 (end-of-study visit for non-responders)
Time frame: 12-week treatment period (Weeks 2 - 13)
Population: Efficacy Analysis Set, composed of all randomized participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Romiplostim | Bleeding Events (Grade 2 or Higher) | 0.41 Events per participant | Standard Deviation 1 |
| Placebo | Bleeding Events (Grade 2 or Higher) | 0.00 Events per participant | Standard Deviation 0 |
p-value: 0.3651Cochran-Mantel-Haenszel
Secondary
Increase in Platelet Count ≥ 20 x 10^9/L Above Baseline for Two Consecutive Weeks
Participant incidence of achieving an increase in platelet count ≥20 x 10\^9/L above baseline for two consecutive weeks during the 12 week treatment period.
Time frame: 12-week treatment period
Population: Efficacy Analysis Set, composed of all randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Romiplostim | Increase in Platelet Count ≥ 20 x 10^9/L Above Baseline for Two Consecutive Weeks | 15 Participants |
| Placebo | Increase in Platelet Count ≥ 20 x 10^9/L Above Baseline for Two Consecutive Weeks | 0 Participants |
p-value: 0.0008Fisher Exact
Secondary
Platelet Count ≥ 50 x 10^9/L for Two Consecutive Weeks
Participant incidence of achieving a platelet count ≥50 x 10\^9/L for two consecutive weeks during the 12 week treatment period.
Time frame: 12-week treatment period
Population: Efficacy Analysis Set, composed of all randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Romiplostim | Platelet Count ≥ 50 x 10^9/L for Two Consecutive Weeks | 15 Participants |
| Placebo | Platelet Count ≥ 50 x 10^9/L for Two Consecutive Weeks | 0 Participants |
p-value: 0.0008Fisher Exact
Secondary
Requirement for Rescue Therapy (as Defined Per Protocol)
Participant required rescue therapy (as defined per protocol) during the 12 week treatment period.
Time frame: 12-week treatment period
Population: Efficacy Analysis Set, composed of all randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Romiplostim | Requirement for Rescue Therapy (as Defined Per Protocol) | 2 Participants |
| Placebo | Requirement for Rescue Therapy (as Defined Per Protocol) | 2 Participants |
p-value: 0.2098Fisher Exact
Secondary
Weeks With Platelet Count ≥ 50 x 10^9/L
The number of weeks with platelet count ≥ 50 x 10\^9/L during the 12 week treatment period.
Time frame: 12-week treatment period
Population: Efficacy Analysis Set, composed of all randomized participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Romiplostim | Weeks With Platelet Count ≥ 50 x 10^9/L | 5.65 Weeks | Standard Deviation 3 |
| Placebo | Weeks With Platelet Count ≥ 50 x 10^9/L | 0.00 Weeks | Standard Deviation 0 |
p-value: 0.0019Cochran-Mantel-Haenszel