Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
Conditions
Keywords
AMG 531, ITP, Long term treatment, Japanese, Romiplostim
Brief summary
The purpose of this study is to assess the safety and efficacy of long term dosing of AMG 531 in thrombocytopenic Japanese subjects with ITP. It is anticipated that AMG 531 will be a safe and well tolerated in long term treatment and that AMG 531 will effectively raise and maintain platelet counts to a desired therapeutic range, when individual dose adjustments based on platelet counts are permitted. This study is available to subjects who have completed any previous AMG 531 ITP study in Japan and meet the eligibility criteria of this study.
Detailed description
Romiplostim was administered by subcutaneous (SC) injection once per week. If subjects entered the extension study within 12 weeks from the last investigational product administration in the previous study and had shown an increase in platelet counts ≥ 20 x 109/L from baseline at least once during the 13-week treatment period (excluding 4 weeks after receiving rescue medication), they were treated with romiplostim at the same weekly dose (last dose on study) received in the previous study. Otherwise, subjects were treated with romiplostim at a starting dose of 3 μg/kg. Dose adjustment based on platelet counts was allowed throughout the treatment period to allow subjects to maintain platelet counts in the target range of ≥ 50 to ≤ 200 x 109/L, up to a maximum permitted dose of 10 μg/kg.
Interventions
BIOLOGICALAMG 531
AMG 531 will be administered by SC injection once per week from Week 1 (Day 1). The maximum permitted dose of AMG 531 is 10 μg/kg. AMG 531 will be supplied as a sterile, white, preservative-free, lyophilized powder in 5 mL glass vials containing 0.6 mg of protein per vial, and a protein concentration of 0.5 mg/mL when reconstituted with 1.2 mL of sterile water for injection.
Sponsors
Kyowa Kirin Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must have previously completed an AMG 531 ITP study in Japan. * Platelet count taken at the screening visit must be \< 50 x 109/L. * Before any study-specific procedure, the appropriate written informed consent must be obtained.
Exclusion criteria
* Any significant change in medical history since completion of the previous AMG 531 ITP study including bone marrow stem cell disorders or new active malignancies * known positive result from a test for neutralizing antibodies to AMG 531 in the previous AMG 531 ITP study * 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 screening visit * received intravenous immunoglobulin, anti-D immunoglobulin, or any drug administered to increase platelet counts (eg, immunosuppressants etc) within 1 week before the screening visit * received anti-malignancy agents (eg, cyclophosphamide, 6-mercaptopurine, vincristine, vinblastine, Interferon-alfa etc) within 4 weeks before the screening visit * received any monoclonal antibody drugs (eg, rituximab etc) within 8 weeks before the screening visit * Less than 4 weeks since receipt of any therapeutic drug or device that is not Ministry of Health, Labor and Welfare (MHLW) approved for any indication before the screening visit (excluding AMG 531) * 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 |
|---|---|---|
| Percentage of Participants With Adverse Events Including Clinically Significant Changes in Laboratory Values. | Through study completion, the median treatment duration (time between first dose and last dose) was 146.0 weeks (range: 12 to 243 weeks) | Subjects who reported at least 1 adverse event after beginning treatment with romiplostim in this study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Anti AMG 531 Antibody Formation | Through study completion, the median treatment duration (time between first dose and last dose) was 146.0 weeks (range: 12 to 243 weeks) | Subjects with positive anti-AMG 531 antibodies (either to the peptide portion of AMG 531 or to the intact molecule) and antibodies that cross-react with endogenous thrombopoietin (TPO) |
| Incidence of Platelet Response (Platelet Response is Defined as a Doubling of Baseline Platelet Counts and More Than 50 x 10^9/L; Baseline Platelet Counts is That Obtained in the Previous Study) | Through study completion, the median treatment duration (time between first dose and last dose) was 146.0 weeks (range: 12 to 243 weeks) | — |
| Percentage of Subjects Able to Reduce or Discontinue Their Concurrent ITP Therapies (for Subjects That Are Receiving Oral Corticosteroids at a Constant Dose and Schedule at the Screening Visit) | Through study completion, the median treatment duration (time between first dose and last dose) was 146.0 weeks (range: 12 to 243 weeks) | — |
| Change From Baseline in Patient-reported Outcome (PRO) Endpoints at Each Time Point (Baseline PRO is Obtained at Day 1 Predose) | By Week 48 | Short Form 36 (SF-36): The SF-36 has 36 questions with 8 domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health. In addition to deriving a score for each of the domains, the SF-36 generates 2 summary scores: a physical component summary (PCS) and a mental component summary (MCS). These 8 domains and 2 summary scores are scored from 0 to 100, with higher scores indicating better health status. The official version in Japanese was used in this study. Euroqol-5 Dimensions (EQ-5D): The EQ-5D is a patient-completed, multidimensional measure of HRQOL. EQ-5D index values range from -0.59 to 1.00. The EQ-5D visual analogue scale (VAS) records the respondents' self-rated health status on a vertical graduated (0 to 100) visual analogue scale. Higher EQ-5D Index and VAS scores represent better health status. The official version in Japanese was used in this study. |
Countries
Japan
Participant flow
Recruitment details
Subjects who had completed any previous romiplostim ITP study in Japan (Studies 20050162/NCT00305435 or 20060216/NCT00603642) were eligible to screen for this study. The study began in October 2006 and continued until romiplostim was commercially available in Japan.
Participants by arm
| Arm | Count |
|---|---|
| AMG 531 AMG531 was administered by SC injection once per week from Week 1 (Day 1). The maximum permitted dose of AMG531 was 10 μg/kg. | 44 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative decision | 3 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | AMG 531 |
|---|---|
| Age, Continuous | 54.9 years STANDARD_DEVIATION 12.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 44 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Japan | 44 participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 44 |
| other Total, other adverse events | 44 / 44 |
| serious Total, serious adverse events | 12 / 44 |
Outcome results
Primary
Percentage of Participants With Adverse Events Including Clinically Significant Changes in Laboratory Values.
Subjects who reported at least 1 adverse event after beginning treatment with romiplostim in this study
Time frame: Through study completion, the median treatment duration (time between first dose and last dose) was 146.0 weeks (range: 12 to 243 weeks)
Population: Subjects in Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AMG 531 | Percentage of Participants With Adverse Events Including Clinically Significant Changes in Laboratory Values. | 100 percentage of participants |
Secondary
Change From Baseline in Patient-reported Outcome (PRO) Endpoints at Each Time Point (Baseline PRO is Obtained at Day 1 Predose)
Short Form 36 (SF-36): The SF-36 has 36 questions with 8 domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health. In addition to deriving a score for each of the domains, the SF-36 generates 2 summary scores: a physical component summary (PCS) and a mental component summary (MCS). These 8 domains and 2 summary scores are scored from 0 to 100, with higher scores indicating better health status. The official version in Japanese was used in this study. Euroqol-5 Dimensions (EQ-5D): The EQ-5D is a patient-completed, multidimensional measure of HRQOL. EQ-5D index values range from -0.59 to 1.00. The EQ-5D visual analogue scale (VAS) records the respondents' self-rated health status on a vertical graduated (0 to 100) visual analogue scale. Higher EQ-5D Index and VAS scores represent better health status. The official version in Japanese was used in this study.
Time frame: By Week 48
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AMG 531 | Change From Baseline in Patient-reported Outcome (PRO) Endpoints at Each Time Point (Baseline PRO is Obtained at Day 1 Predose) | Change in SF-36 Physical Component at Week 48 | 1.13 score on a scale | Standard Deviation 6.85 |
| AMG 531 | Change From Baseline in Patient-reported Outcome (PRO) Endpoints at Each Time Point (Baseline PRO is Obtained at Day 1 Predose) | Change in SF-36 bodily pain at Week 48 | -0.87 score on a scale | Standard Deviation 13.42 |
| AMG 531 | Change From Baseline in Patient-reported Outcome (PRO) Endpoints at Each Time Point (Baseline PRO is Obtained at Day 1 Predose) | Change in SF-36 General Health Perception at W48 | 1.30 score on a scale | Standard Deviation 5.14 |
| AMG 531 | Change From Baseline in Patient-reported Outcome (PRO) Endpoints at Each Time Point (Baseline PRO is Obtained at Day 1 Predose) | Change in SF-36 Vitality at Week 48 | 1.12 score on a scale | Standard Deviation 8.42 |
| AMG 531 | Change From Baseline in Patient-reported Outcome (PRO) Endpoints at Each Time Point (Baseline PRO is Obtained at Day 1 Predose) | Change in SF-36 Social Functioning at Week 48 | 1.22 score on a scale | Standard Deviation 8.56 |
| AMG 531 | Change From Baseline in Patient-reported Outcome (PRO) Endpoints at Each Time Point (Baseline PRO is Obtained at Day 1 Predose) | Change in SF-36 Role Emotional at Week 48 | 1.84 score on a scale | Standard Deviation 12.82 |
| AMG 531 | Change From Baseline in Patient-reported Outcome (PRO) Endpoints at Each Time Point (Baseline PRO is Obtained at Day 1 Predose) | Change in SF-36 Mental Health at Week 48 | -1.42 score on a scale | Standard Deviation 9.04 |
| AMG 531 | Change From Baseline in Patient-reported Outcome (PRO) Endpoints at Each Time Point (Baseline PRO is Obtained at Day 1 Predose) | Change in SF-36 Mental Component at Week 48 | 0.33 score on a scale | Standard Deviation 9.19 |
| AMG 531 | Change From Baseline in Patient-reported Outcome (PRO) Endpoints at Each Time Point (Baseline PRO is Obtained at Day 1 Predose) | Change in EQ-5D Index score at Week 48 | 0.02 score on a scale | Standard Deviation 0.12 |
| AMG 531 | Change From Baseline in Patient-reported Outcome (PRO) Endpoints at Each Time Point (Baseline PRO is Obtained at Day 1 Predose) | Change in EQ-5D VAS score at Week 48 | 6.13 score on a scale | Standard Deviation 16.48 |
| AMG 531 | Change From Baseline in Patient-reported Outcome (PRO) Endpoints at Each Time Point (Baseline PRO is Obtained at Day 1 Predose) | Change in SF-36 physical functioning at Week 48 | 0.68 score on a scale | Standard Deviation 7.19 |
| AMG 531 | Change From Baseline in Patient-reported Outcome (PRO) Endpoints at Each Time Point (Baseline PRO is Obtained at Day 1 Predose) | Change in SF-36 role physical at Week 48 | 2.30 score on a scale | Standard Deviation 10.43 |
Secondary
Incidence of Anti AMG 531 Antibody Formation
Subjects with positive anti-AMG 531 antibodies (either to the peptide portion of AMG 531 or to the intact molecule) and antibodies that cross-react with endogenous thrombopoietin (TPO)
Time frame: Through study completion, the median treatment duration (time between first dose and last dose) was 146.0 weeks (range: 12 to 243 weeks)
Population: Subjects with at least 1 immunoassay available
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AMG 531 | Incidence of Anti AMG 531 Antibody Formation | Positive for romiplostim-neutralizing antibodies | 0 percentage of participants |
| AMG 531 | Incidence of Anti AMG 531 Antibody Formation | Positive for TPO-neutralizing antibodies | 0 percentage of participants |
Secondary
Incidence of Platelet Response (Platelet Response is Defined as a Doubling of Baseline Platelet Counts and More Than 50 x 10^9/L; Baseline Platelet Counts is That Obtained in the Previous Study)
Time frame: Through study completion, the median treatment duration (time between first dose and last dose) was 146.0 weeks (range: 12 to 243 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AMG 531 | Incidence of Platelet Response (Platelet Response is Defined as a Doubling of Baseline Platelet Counts and More Than 50 x 10^9/L; Baseline Platelet Counts is That Obtained in the Previous Study) | 95.5 percentage of participants |
Secondary
Percentage of Subjects Able to Reduce or Discontinue Their Concurrent ITP Therapies (for Subjects That Are Receiving Oral Corticosteroids at a Constant Dose and Schedule at the Screening Visit)
Time frame: Through study completion, the median treatment duration (time between first dose and last dose) was 146.0 weeks (range: 12 to 243 weeks)
Population: Subjects who were receiving concurrent ITP therapy at baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AMG 531 | Percentage of Subjects Able to Reduce or Discontinue Their Concurrent ITP Therapies (for Subjects That Are Receiving Oral Corticosteroids at a Constant Dose and Schedule at the Screening Visit) | 100 percentage of participants |