Idiopathic Thrombocytopenic Purpura
Conditions
Keywords
AMG 531, Idiopathic Thrombocytopenic Purpura, ITP, Thrombocytopenia, Japan, Placebo controlled, Phase 3
Brief summary
The purpose of this study is to evaluate the efficacy and safety of AMG 531 compared with placebo in thrombocytopenic Japanese subjects with immune (idiopathic) thrombocytopenic purpura (ITP) .
Interventions
DRUGPlacebo
Subcutaneously administered, once a week, for 12 weeks
DRUGAMG 531
Subcutaneously administered, once a week, for 12 weeks
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Japanese patients with diagnosis of ITP according to the diagnostic criteria proposed by Research Committee for Idiopathic Hematopoietic Disorders of the Ministry of Health, Labour and Welfare \[MHLW\] (revised in 1990) at least 6 months before the first screening visit * The mean of the 3 scheduled platelet counts taken at the scheduled visits during the screening period must be ≤ 30 x 10\^9/L, with no individual count \> 35 x 10\^9/L * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 * Subjects must be ≥ 20 years of age at the time of obtaining the informed consent * Have received at least 1 prior treatment for ITP * If known Helicobacter pylori positive, having completed one course of Helicobacter pylori eradication therapy at least 12 weeks before the first screening visit * A hemoglobin value taken at scheduled visit during the screening period must be ≥ 10 g/dL * A serum creatinine concentration taken at scheduled visit during the screening period must be ≤ 2 mg/dL * Adequate liver function, as evidenced by a total bilirubin taken at scheduled visit during the screening period ≤ 1.5 times of the upper limit of the normal range (except for patients with a confirmed diagnosis of Gilbert's Disease) or an alanine aminotransferase and aspartate aminotransferase taken at the screening visit ≤ 3 times of the upper limit of the normal range
Exclusion criteria
* Any known history of bone marrow stem cell disorder. Any abnormal bone marrow findings other than those typical of ITP. * Any active malignancy. If prior history of cancer other than basal cell carcinoma or cervical carcinoma in situ, no treatment or active disease within 5 years before the first screening visit. * Documented diagnosis of arterial thrombosis (eg, stroke, transient ischemic attack, or myocardial infarction); history of venous thrombosis (eg, deep vein thrombosis, pulmonary embolism) and receiving anticoagulation therapy at the first screening visit. * Documented diagnosis of anti phospholipid antibody syndrome * Currently receiving any treatment for ITP except oral corticosteroids, azathioprine and/or danazol administered at a constant dose and schedule from at least 4 weeks prior to the first screening visit * Received intravenous immunoglobulin, anti D immunoglobulin, or any drug administered to increase platelet counts (eg, immunosuppressants except azathioprine) within 2 weeks before the first screening visit * Have had a splenectomy for any reason within 12 weeks before the first screening visit * Past or present participation in any study evaluating pegacaristim (polyethylene glycol-conjugated recombinant human megakaryocyte growth and development factor, KRN9000), Eltrombopag (SB 497115), recombinant human thrombopoietin, AMG 531, or other Mpl stimulation product * Received hematopoietic growth factors (eg, granulocyte colony stimulating factor, macrophage colony stimulating factor, erythropoietin, interleukin 11) for any reason within 4 weeks before the first screening visit * Received any anti malignancy agents (eg, cyclophosphamide, 6 mercaptopurine, vincristine, vinblastine, Interferon alfa) for any reason within 8 weeks before the first screening visit * Received any monoclonal antibody drugs (eg, rituximab) for any reason within 14 weeks before the first screening visit * Less than 4 weeks since receipt of any therapeutic drug or device that is not MHLW approved for any indication before the first screening visit * Pregnant or breast feeding * Subjects of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator * Known severe drug hypersensitivity * Concerns for subject's compliance with the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weeks With Weekly Platelet Response | 12 weeks (Weeks 2 - 13) | Number of weeks with weekly platelet response. A weekly platelet response is defined as a platelet count of ≥ 50 x 10\^9/L on a weekly scheduled dose day from week 2 to week 13. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Increased Platelet Count From Baseline of at Least 20 x 10^9/L | Baseline, 12 weeks (Weeks 2 - 13) | An increase in platelet count of at least 20 x 10\^9/L from baseline within the participant during the treatment period. Increase was calculated as the maximum observed platelet count during the treatment period minus the baseline platelet count. |
| Change From Baseline in Mean of Last 4 Weekly Platelet Counts | 12 weeks (Weeks 2 - 13) | Change from baseline in the mean of the last 4 weekly platelet counts from week 2 to week 13. |
| Weeks With Platelet Count Between 50 and 200 | 12 weeks (Weeks 2 - 13) | Number of weeks with platelet count between 50 x 10\^9/L and 200 x 10\^9/L inclusive during week 2 to week 13. |
| Rescue Medication(s) | 12 weeks (Weeks 2 - 13) | Requirement for rescue medication(s) during treatment by the participant |
Participant flow
Recruitment details
Participants were enrolled from 20 November 2007 through 11 December 2008
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo administered subcutaneously once weekly for 12 weeks | 12 |
| Romiplostim Romiplostim administered subcutaneously once weekly for 12 weeks at a starting dose of 3 µg/kg | 22 |
| Total | 34 |
Baseline characteristics
| Characteristic | Placebo | Romiplostim | Total |
|---|---|---|---|
| Age, Continuous | 47.6 Years STANDARD_DEVIATION 13.4 | 58.5 Years STANDARD_DEVIATION 12.6 | 54.7 Years STANDARD_DEVIATION 13.7 |
| Platelet Count | 15.8 10^9/L STANDARD_DEVIATION 8.6 | 18.4 10^9/L STANDARD_DEVIATION 8.3 | 17.5 10^9/L STANDARD_DEVIATION 8.4 |
| Race/Ethnicity, Customized Japanese | 12 Participants | 22 Participants | 34 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 10 Participants | 14 Participants | 24 Participants |
| Sex: Female, Male Male | 2 Participants | 8 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 12 | 16 / 22 |
| serious Total, serious adverse events | 1 / 12 | 2 / 22 |
Outcome results
Primary
Weeks With Weekly Platelet Response
Number of weeks with weekly platelet response. A weekly platelet response is defined as a platelet count of ≥ 50 x 10\^9/L on a weekly scheduled dose day from week 2 to week 13.
Time frame: 12 weeks (Weeks 2 - 13)
Population: Full Analysis Set, composed of all randomized participants who received at least 1 dose of romiplostim or placebo
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Weeks With Weekly Platelet Response | 0.0 Weeks |
| Romiplostim | Weeks With Weekly Platelet Response | 11.0 Weeks |
p-value: <0.0001Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Mean of Last 4 Weekly Platelet Counts
Change from baseline in the mean of the last 4 weekly platelet counts from week 2 to week 13.
Time frame: 12 weeks (Weeks 2 - 13)
Population: Full Analysis Set, composed of all randomized participants who received at least 1 dose of romiplostim or placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mean of Last 4 Weekly Platelet Counts | 2.3 10^9/L | Standard Deviation 6.5 |
| Romiplostim | Change From Baseline in Mean of Last 4 Weekly Platelet Counts | 109.7 10^9/L | Standard Deviation 88.5 |
p-value: 0.0003ANCOVA
Secondary
Increased Platelet Count From Baseline of at Least 20 x 10^9/L
An increase in platelet count of at least 20 x 10\^9/L from baseline within the participant during the treatment period. Increase was calculated as the maximum observed platelet count during the treatment period minus the baseline platelet count.
Time frame: Baseline, 12 weeks (Weeks 2 - 13)
Population: Full Analysis Set, composed of all randomized participants who received at least 1 dose of romiplostim or placebo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Increased Platelet Count From Baseline of at Least 20 x 10^9/L | 3 Participants |
| Romiplostim | Increased Platelet Count From Baseline of at Least 20 x 10^9/L | 21 Participants |
p-value: <0.0001Fisher Exact
Secondary
Rescue Medication(s)
Requirement for rescue medication(s) during treatment by the participant
Time frame: 12 weeks (Weeks 2 - 13)
Population: Full Analysis Set, composed of all randomized participants who received at least 1 dose of romiplostim or placebo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Rescue Medication(s) | 2 Participants |
| Romiplostim | Rescue Medication(s) | 2 Participants |
p-value: 0.6015Fisher Exact
Secondary
Weeks With Platelet Count Between 50 and 200
Number of weeks with platelet count between 50 x 10\^9/L and 200 x 10\^9/L inclusive during week 2 to week 13.
Time frame: 12 weeks (Weeks 2 - 13)
Population: Full Analysis Set, composed of all randomized participants who received at least 1 dose of romiplostim or placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Weeks With Platelet Count Between 50 and 200 | 0.2 Weeks | Standard Deviation 0.4 |
| Romiplostim | Weeks With Platelet Count Between 50 and 200 | 6.3 Weeks | Standard Deviation 3.2 |
p-value: <0.0001Wilcoxon (Mann-Whitney)