Idiopathic Thrombocytopenic Purpura, Thrombocytopenia, Thrombocytopenic Purpura
Conditions
Keywords
Platelet, AMG 531, Thrombopoietin, blood disorder, bleeding disorder, immune thrombocytopenic purpura, idiopathic thrombocytopenic purpura, immune (idiopathic) thrombocytopenic purpura, TPO, thrombopoietic protein
Brief summary
This protocol will provide open label romiplostim to adult thrombocytopenic subjects. Romiplostim will be administered by subcutaneous injection once per week. Dose adjustment will be based on platelet counts, and will be allowed throughout the duration of the study. Rescue therapies are allowed at any time during the study. Reductions in concurrent ITP therapies may occur at any time when platelet counts are \> 50,000.
Interventions
BIOLOGICALRomiplostim
Romiplostim will be administered subcutaneously QW. Romiplostim will be manufactured and packaged and distributed using Amgen's clinical study investigational product distribution procedures. Romiplostim is presented as a lyophilized, white powder in 5.0 mL glass vials.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is ≥ 18 years of age * Subject has a diagnosis of immune (idiopathic) thrombocytopenic purpura per the American Society of Hematology guidelines * If Subject is \> 60 years of age, subject has a written bone marrow aspiration and/or biopsy report consistent with a diagnosis of ITP * Subject has received at least 1 prior therapy for ITP * Subject's platelet count is ≤ 30,000 or the subject is experiencing bleeding that is uncontrolled with conventional therapies * Subject (or legally-acceptable representative) is willing and able to provide written informed consent
Exclusion criteria
* Subject has a history of hematological malignancy, myeloproliferative disorder, myelodysplastic syndrome (MDS), or bone marrow stem cell disorder * Subject has participated in any study evaluating PEG-rHuMGDF, recombinant human thrombopoietin (rHuTPO), or related platelet product * Subject has a known hypersensitivity to any recombinant E coli-derived product * Subject has received any therapeutic drug or device that is not approved by the local regulatory health agency for any indication within 4 weeks of Screening * Subject is of reproductive potential and is not using adequate contraceptive precautions, in the judgment of the investigator * Subject is pregnant or breast feeding * Investigator has concerns regarding the subject's ability to comply with the protocol procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | Duration of Treatment plus 30 days or End of Study (whichever is later). Approximately 205 weeks. | One or more occurences of one or more adverse events within the participant during the study. Participants with more than one event were only counted once |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Platelet Response (Definition 1) | Duration of treatment (up to 201 weeks) | Platelet response using definition1 . (a doubling of baseline platelet count and a platelet count of \>=50 x 10\^9/L |
| Platelet Response (Definition 2) | Duration of treatment (up to 201 weeks) | Platelet response using definition 2 (a platelet count increase of \>=20 x 109/L from baseline) |
Participant flow
Recruitment details
First Subject Enrolled: 24Feb2005 Last Subject Enrolled: 05Jan2010
Participants by arm
| Arm | Count |
|---|---|
| Romiplostim (AMG 531) Cohort 1 Romiplostim administered to participants subcutaneously weekly based on platelet counts. Participants were enrolled under the original protocol or protocol amendments 1-3 where starting dose was 3mcg/kg. | 168 |
| Romiplostim (AMG 531) Cohort 2 Romiplostim administered to participants subcutaneously weekly based on platelet counts. Participants were enrolled under protocol amendments 4 where starting dose was 1mcg/kg. | 239 |
| Total | 407 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 10 |
| Overall Study | Death | 6 | 8 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Noncompliance | 1 | 0 |
| Overall Study | Other | 11 | 2 |
| Overall Study | Physician Decision | 8 | 2 |
| Overall Study | Pregnancy | 0 | 2 |
| Overall Study | Protocol-specified Criteria | 3 | 12 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Requirement for alternative therapy | 7 | 15 |
| Overall Study | Withdrawal by Subject | 10 | 12 |
Baseline characteristics
| Characteristic | Romiplostim (AMG 531) Cohort 1 | Romiplostim (AMG 531) Cohort 2 | Total |
|---|---|---|---|
| Age, Continuous | 53.6 years STANDARD_DEVIATION 17 | 54.1 years STANDARD_DEVIATION 18 | 53.9 years STANDARD_DEVIATION 17.6 |
| Race/Ethnicity, Customized Asian | 5 participants | 3 participants | 8 participants |
| Race/Ethnicity, Customized Black or African American | 5 participants | 1 participants | 6 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 7 participants | 2 participants | 9 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Other | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized White or Caucasian | 149 participants | 232 participants | 381 participants |
| Sex: Female, Male Female | 94 Participants | 150 Participants | 244 Participants |
| Sex: Female, Male Male | 74 Participants | 89 Participants | 163 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 155 / 168 | 188 / 239 |
| serious Total, serious adverse events | 61 / 168 | 61 / 239 |
Outcome results
Primary
Adverse Events
One or more occurences of one or more adverse events within the participant during the study. Participants with more than one event were only counted once
Time frame: Duration of Treatment plus 30 days or End of Study (whichever is later). Approximately 205 weeks.
Population: Safety Analysis Set, comprised of all participants who received at least one dose of romiplostim
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Romiplostim (AMG 531) Cohort 1 | Adverse Events | 162 participants |
| Romiplostim (AMG 531) Cohort 2 | Adverse Events | 215 participants |
Secondary
Platelet Response (Definition 1)
Platelet response using definition1 . (a doubling of baseline platelet count and a platelet count of \>=50 x 10\^9/L
Time frame: Duration of treatment (up to 201 weeks)
Population: Full Analysis Set, all enrolled participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Romiplostim (AMG 531) Cohort 1 | Platelet Response (Definition 1) | 156 Participants |
| Romiplostim (AMG 531) Cohort 2 | Platelet Response (Definition 1) | 214 Participants |
Secondary
Platelet Response (Definition 2)
Platelet response using definition 2 (a platelet count increase of \>=20 x 109/L from baseline)
Time frame: Duration of treatment (up to 201 weeks)
Population: Full Analysis Set, all enrolled participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Romiplostim (AMG 531) Cohort 1 | Platelet Response (Definition 2) | 160 Participants |
| Romiplostim (AMG 531) Cohort 2 | Platelet Response (Definition 2) | 220 Participants |