Idiopathic Thrombocytopenic Purpura
Conditions
Keywords
ITP
Brief summary
The purpose of this study is to describe the number of months with a platelet response over a 12 month treatment period and to describe ITP remission rates in adults with ITP receiving romiplostim.
Detailed description
The study includes a 4-week screening period, a 12-month romiplostim treatment period, and a romiplostim dose-tapering period. During the 12-month treatment period romiplostim doses could be increased or decreased to maintain a platelet count between ≥ 50 x 10\^9/L and ≤ 200 x 10\^9/L. Participants who dose reduce such that they no longer require treatment with romiplostim during the 12-month treatment period will continue with all required study procedures up to 12 months and will be monitored for ITP remission for at least 6 months. At the completion of the 12-month treatment period, participants receiving only romiplostim and with a platelet count ≥ 50 x 10\^9/L will enter the tapering period, during which the romiplostim dose will be decreased by 1 µg/kg every 2 weeks, for up to 19 weeks. If a participant maintains a platelet count of ≥ 50 x 10\^9/L in the absence of romiplostim and all medications for ITP (concomitant or rescue), the participant will be followed for at least 6 months to confirm the incidence of ITP remission. If a participant's platelet count falls below 50 x 10\^9/L and the participant has tapered off treatment with romiplostim, the participant will enter the stabilization period and reinitiate romiplostim for up to 8 weeks.
Interventions
BIOLOGICALRomiplostim
Romiplostim will be administered weekly by subcutaneous injection
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 has been diagnosed with primary ITP according to the American Society of Hematology (ASH) guidelines (George et al, 1996) and previously received only 1st line therapies. First line therapy is defined as corticosteroids, immunoglobulin G (IVIG), anti-D and vinca alkaloids (used for the treatment of ITP related thrombocytopenia only). A platelet transfusion at any time during the six month period since the original diagnosis would not exclude the subject from study participation * Initial diagnosis of primary ITP within 6 months of enrollment * Age ≥ 18 years at screening * A single platelet count ≤ 30 x 10⁹/L at any time during the screening period * Subject or subject's legally acceptable representative has provided informed consent
Exclusion criteria
* Known history of a bone marrow stem cell disorder * Surgical resection of the spleen * Subject has a history of cancer or current malignancy other than basal cell carcinoma or cervical cancer in-situ with active treatment or disease within 5 years of screening * Known history of congenital thrombocytopenia * Known history of hepatitis B, hepatitis C, or human immunodeficiency virus * Positive H. pylori by urea breath test or stool antigen test at screening * Known history of systemic lupus erythematosus, Evans syndrome, or autoimmune neutropenia * Known history of antiphospholipid antibody syndrome or positive for lupus anticoagulant * Known history of disseminated intravascular coagulation, hemolytic uremic syndrome, or thrombotic thrombocytopenic purpura * Previous history of recurrent venous thromboembolism or thrombotic events or an occurrence within 5 years of enrollment. * Previous use of romiplostim, pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), eltrombopag, recombinant human thrombopoietin (rHuTPO) or any platelet producing agent * Rituximab (for any indication) or mercaptopurine (6-MP) or anticipated use during the time of the proposed study * All hematopoietic growth factors including interleukin-11 (IL-11) (oprelvekin) within 4 weeks before the screening visit * Alkylating agents use at any time before or during the screening visit or anticipated during the time of the proposed study * Known hypersensitivity to any recombinant E. coli-derived product (eg, Infergen, Neupogen, Somatropin, and Actimmune) * Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s) * Subject will have any other investigational procedures performed while enrolled in this clinical study * Subject is pregnant or breast feeding, or planning to become pregnant within 5 weeks after the end of treatment * Female subject of child bearing potential is not willing to use, in combination with her partner, highly effective contraception during treatment and for 4 weeks after the end of treatment * Subject has previously enrolled into a romiplostim study * Subject will not be available for protocol required study visits, to the best of the subject's and investigator's knowledge * Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Months With Platelet Response During the 12-Month Treatment Period | 12 months | The primary endpoint was the number of months a participant achieved a platelet response during the 12-month treatment period. A platelet response for any 1 month was defined as the median of platelet counts measured in the month ≥ 50 x 10\^9/L. Platelet counts within 4 weeks following a rescue medication use or following splenectomy were considered non-response. Months without any platelet count measurement were considered as months with no platelet response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ITP Remission | Up to 24 months | ITP remission was defined as maintaining every platelet count ≥ 50 x 10\^9/L for at least 6 months in the absence of romiplostim and any other therapies to treat ITP. |
| Percentage of Participants With Splenectomy During the 12-month Treatment Period | 12 months | If treatment with romiplostim was deemed ineffective or intolerable by the investigator, a splenectomy may have been performed. |
| Number of Participants With Adverse Events | From first dose date of romiplostim to end of study (up to 24 months). | An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. A serious adverse event is defined as an adverse event that meets at least one of the following serious criteria: • fatal • life threatening • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • congenital anomaly/birth defect • other significant medical hazard. Whether an adverse event was treatment-related (TRAE) or not was determined by investigator. |
| Number of Participants Who Developed Antibodies to Romiplostim | Baseline and at end of treatment (based on response to treatment, this could occur between 12 months and approximately 18 months) | The number of participants who developed antibody formation (defined as negative at baseline and positive at post-baseline, transient or persistent) to romiplostim, endogenous thrombopoietin (eTPO), and thrombopoietin mimetic peptide (TMP, the peptide component of romiplostim) was summarized. |
Countries
Australia, Czechia, France, Germany, Italy, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
Ninety-eight adults with immune thrombocytopenia purpura (ITP) were screened for the study; 23 were considered screen failures. Seventy-five participants were enrolled at 32 study centers in Australia, the European Union, and North America from 30 November 2010 to 21 September 2012.
Pre-assignment details
The study included a 12-month romiplostim treatment period, and a romiplostim dose-tapering period. Participants who maintained a platelet count of ≥ 50 x 10\^9/L in the absence of romiplostim and all medications for ITP (concomitant or rescue) were followed for at least 6 months to confirm the incidence of ITP remission.
Participants by arm
| Arm | Count |
|---|---|
| Romiplostim Participants received romiplostim administered weekly by subcutaneous injection during the 12-month treatment period. The starting dose was 1 μg/kg with weekly dose increases in increments of 1 μg/kg/week to a maximum dose of 10 μg/kg to reach a target platelet count of ≥ 50 x 10\^9/L. At the completion of the 12-month treatment period, participants receiving only romiplostim and with a platelet count ≥ 50 x 10\^9/L entered the tapering period, during which the romiplostim dose was decreased by 1 µg/kg every 2 weeks, for up to 19 weeks. Participants who had tapered off treatment with romiplostim and whose platelet count dropped below 50 x 10\^9/L could reinitiate romiplostim for up to 8 weeks. | 75 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Protocol Deviation | 1 |
| Overall Study | Requirement for alternative therapy | 5 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Romiplostim |
|---|---|
| Age, Continuous | 44.5 years STANDARD_DEVIATION 18.7 |
| Ethnicity Hispanic/Latino | 6 participants |
| Ethnicity Not Hispanic/Latino | 69 participants |
| Platelet Count at Screening | 19.78 x 10^9/L STANDARD_DEVIATION 15.8 |
| Race American Indian or Alaska Native | 0 participants |
| Race Asian | 1 participants |
| Race Black (or African American) | 1 participants |
| Race Native Hawaiian or Other Pacific Islander | 0 participants |
| Race Other | 0 participants |
| Race Unknown | 1 participants |
| Race White | 72 participants |
| Sex: Female, Male Female | 44 Participants |
| Sex: Female, Male Male | 31 Participants |
| Time since ITP diagnosis | 2.2 months |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 50 / 75 |
| serious Total, serious adverse events | 17 / 75 |
Outcome results
Primary
Number of Months With Platelet Response During the 12-Month Treatment Period
The primary endpoint was the number of months a participant achieved a platelet response during the 12-month treatment period. A platelet response for any 1 month was defined as the median of platelet counts measured in the month ≥ 50 x 10\^9/L. Platelet counts within 4 weeks following a rescue medication use or following splenectomy were considered non-response. Months without any platelet count measurement were considered as months with no platelet response.
Time frame: 12 months
Population: Safety Analysis Set includes all participants who received at least 1 dose of romiplostim.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Romiplostim | Number of Months With Platelet Response During the 12-Month Treatment Period | 9.2 months | Standard Error 0.4 |
95% CI: [8.3, 10.1]
Comparison: Bootstrap analysis95% CI: [8.3, 10]
Secondary
Number of Participants Who Developed Antibodies to Romiplostim
The number of participants who developed antibody formation (defined as negative at baseline and positive at post-baseline, transient or persistent) to romiplostim, endogenous thrombopoietin (eTPO), and thrombopoietin mimetic peptide (TMP, the peptide component of romiplostim) was summarized.
Time frame: Baseline and at end of treatment (based on response to treatment, this could occur between 12 months and approximately 18 months)
Population: Safety analysis set participants with available results
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Romiplostim | Number of Participants Who Developed Antibodies to Romiplostim | Antibodies to romiplostim | 2 participants |
| Romiplostim | Number of Participants Who Developed Antibodies to Romiplostim | Antibodies to TPO | 1 participants |
| Romiplostim | Number of Participants Who Developed Antibodies to Romiplostim | Antibodies to TMP | 2 participants |
| Romiplostim | Number of Participants Who Developed Antibodies to Romiplostim | Neutralizing antibodies to romiplostim | 1 participants |
| Romiplostim | Number of Participants Who Developed Antibodies to Romiplostim | Neutralizing antibodies to TPO | 0 participants |
| Romiplostim | Number of Participants Who Developed Antibodies to Romiplostim | Neutralizing antibodies to TMP | 0 participants |
Secondary
Number of Participants With Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. A serious adverse event is defined as an adverse event that meets at least one of the following serious criteria: • fatal • life threatening • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • congenital anomaly/birth defect • other significant medical hazard. Whether an adverse event was treatment-related (TRAE) or not was determined by investigator.
Time frame: From first dose date of romiplostim to end of study (up to 24 months).
Population: Safety analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Romiplostim | Number of Participants With Adverse Events | All adverse events | 63 participants |
| Romiplostim | Number of Participants With Adverse Events | Treatment-related adverse event | 21 participants |
| Romiplostim | Number of Participants With Adverse Events | Serious adverse events | 17 participants |
| Romiplostim | Number of Participants With Adverse Events | Leading to discontinuation of romiplostim | 4 participants |
| Romiplostim | Number of Participants With Adverse Events | Leading to discontinuation from study | 3 participants |
| Romiplostim | Number of Participants With Adverse Events | Fatal adverse events | 0 participants |
| Romiplostim | Number of Participants With Adverse Events | Treatment-related serious adverse events | 3 participants |
| Romiplostim | Number of Participants With Adverse Events | TRAE leading to discontinuation of romiplostim | 2 participants |
| Romiplostim | Number of Participants With Adverse Events | TRAE leading to discontinuation from study | 2 participants |
| Romiplostim | Number of Participants With Adverse Events | Treatment-related fatal adverse events | 0 participants |
Secondary
Percentage of Participants With ITP Remission
ITP remission was defined as maintaining every platelet count ≥ 50 x 10\^9/L for at least 6 months in the absence of romiplostim and any other therapies to treat ITP.
Time frame: Up to 24 months
Population: Safety analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Romiplostim | Percentage of Participants With ITP Remission | 32.0 percentage of participants |
Secondary
Percentage of Participants With Splenectomy During the 12-month Treatment Period
If treatment with romiplostim was deemed ineffective or intolerable by the investigator, a splenectomy may have been performed.
Time frame: 12 months
Population: Safety analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Romiplostim | Percentage of Participants With Splenectomy During the 12-month Treatment Period | 1.3 percentage of participants |