Immune Thrombocytopenia
Conditions
Keywords
ITP
Brief summary
Evaluate the efficacy, safety, and PK of avatrombopag given for 26 weeks in Japanese adults with chronic immune thrombocytopenia (ITP).
Detailed description
This Phase 3, multicenter, open label study will evaluate the efficacy, safety, and population pharmacokinetics (PK) of avatrombopag in Japanese adults with chronic ITP. At least 19 subjects will be enrolled. The study will consist of 3 phases: Pre-enrollment, Primary Investigation, and Extension Phase until market authorization in Japan.
Interventions
Avatrombopag 20 mg given once daily (initial dose). Dosage adjustments were determined by the physician to maintain a platelet count between 50 x 10\^9 to 200 x 10\^9 as defined in the protocol and in accordance with overseas labeling.
Sponsors
Sobi, Inc.
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 a confirmed diagnosis of chronic immune thrombocytopenia (ITP) (≥12 months duration) and has had an insufficient response to a previous ITP treatment, in the opinion of the Investigator. * Subject has an average of 2 platelet counts \<30×10\^9/L (no single count can be \>35×10\^9/L). The 2 samples must be obtained ≥48 hours and ≤2 weeks apart.
Exclusion criteria
* Subjects with known secondary immune thrombocytopenia (e.g., with known Helicobacter pylori-induced ITP, subjects infected with known human immunodeficiency virus (HIV) or hepatitis C virus (HCV) or subjects with known systemic lupus erythematosus). * Subjects with known inherited thrombocytopenia (e.g., Myosin Heavy Chain 9 (MYH-9) disorders) or hereditary thrombophilic disorders (e.g., Factor V Leiden, antithrombin III deficiency). * History of myelodysplastic syndrome (MDS). * History of arterial or venous thrombosis. * Subjects with a history of significant cardiovascular disease (e.g., congestive heart failure (CHF) New York Heart Association Grade III/IV, arrhythmia known to increase the risk of thromboembolic events \[e.g., atrial fibrillation\], angina, coronary artery stent placement, angioplasty, coronary artery bypass grafting). * Subjects with a history of cirrhosis, portal hypertension, or chronic active hepatitis. * Subjects with concurrent malignant disease or receiving cytotoxic chemotherapy for a reason other than ITP treatment. * Use of immunoglobulins (IVIg and anti-D) or corticosteroid rescue therapy within 1 week of Day 1/Baseline. * Splenectomy or use of rituximab within 12 weeks of Day 1/Baseline. * Use of romiplostim or eltrombopag within 1 week of Day 1/Baseline. * Use of chronic corticosteroid treatment or azathioprine within 4 weeks of Day 1/Baseline, unless receiving a stable dose for at least 4 weeks. * Use of mycophenolate mofetil, cyclosporin A, or danazol within 4 weeks of Day 1/Baseline, unless receiving a stable dose for at least 12 weeks. * Use of cyclophosphamide or vinca alkaloid regimens within 4 weeks of Baseline Visit. * Currently receiving moderate or strong dual inhibitors/inducers of CYP2C9 and CYP3A4. * Serum creatinine ≥1.5× the upper limit of normal (ULN). * Serum bilirubin ≥2×ULN. * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3×ULN. * Females who are pregnant (positive beta-human chorionic gonadotropin (β-hCG) test) or breastfeeding. * Received treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) before Day 1/Baseline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Number of Weeks of Platelet Response | 26 weeks of active treatment | Cumulative number of weeks in which the platelet count is ≥50×10\^9/L during 26 weeks of treatment in the absence of rescue therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate at Day 8 | Day 8 | Proportion of subjects with a platelet response ≥50×10\^9/L at Day 8 in the absence of rescue therapy |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Avatrombopag Avatrombopag 20 mg oral tablet
Avatrombopag 20 mg given once daily (initial dose). Dose adjustments were determined by the physician to maintain a platelet count between 50 x 10\^9 to 200 x 10\^9 as defined in the protocol and in accordance with the overseas labeling. | 19 |
| Total | 19 |
Baseline characteristics
| Characteristic | Avatrombopag |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 56.0 years STANDARD_DEVIATION 16.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 19 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 | 19 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 19 |
| other Total, other adverse events | 18 / 19 |
| serious Total, serious adverse events | 3 / 19 |
Outcome results
Primary
Cumulative Number of Weeks of Platelet Response
Cumulative number of weeks in which the platelet count is ≥50×10\^9/L during 26 weeks of treatment in the absence of rescue therapy.
Time frame: 26 weeks of active treatment
Population: Full analysis set of core phase
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Avatrombopag | Cumulative Number of Weeks of Platelet Response | 13.47 cumulative number of weeks | Standard Deviation 9.002 |
Secondary
Response Rate at Day 8
Proportion of subjects with a platelet response ≥50×10\^9/L at Day 8 in the absence of rescue therapy
Time frame: Day 8
Population: Full analysis set of core phase
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Avatrombopag | Response Rate at Day 8 | 12 Participants |