Aplastic Anemia
Conditions
Keywords
Aplastic Anemia, globulin, ATG, Anti-human Thymocyte Immunogloblin
Brief summary
The purpose of the study is to assess the efficacy and safety of PF-06462700 administered intravenously at 40 mg/kg/day for 4 days in Japanese participants with moderate and above aplastic anemia for making an approval application in Japan.
Interventions
BIOLOGICALPF-06462700
PF-06462700 is classified as an immunosuppressant/ immunosuppressive agent. It is the purified, concentrated, and sterile gamma globulin, primarily monomeric immunoglobulin G (IgG), from hyperimmune serum of horses that are immunized with human thymus lymphocytes.
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female participants between the ages of 2 years and more, inclusive, at Visit 1 (Screening). * Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. * Have a clinical diagnosis of aplastic anemia by bone marrow aspiration/biopsy findings and/or magnetic resonance imaging (MRI) etc. * Must meet the following criteria of moderate and above aplastic anemia * Capable of giving signed informed consent/assent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD)/assent document and in this protocol.
Exclusion criteria
* Eligible and willing to have a sibling allogeneic stem cell transplantation. * Evidence of a myelodysplastic syndrome (except for refractory cytopenia in children), as well as other primitive marrow disease. * History or clinical suspicion of congenital aplastic anemia (Fanconi anemia, Congenital keratosis, etc). * History of malignant tumors with active disease within 5 years from study participation. * Participants who are clearly infected with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and human T-cell leukemia virus type 1 (HTLV-1). * Pregnant or breast-feeding participants. * Participants with severe hepatic, renal or cardiac failure, or any other life-threatening concurrent \[aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or total bilirubin values \>5 × upper limit of normal (ULN), and/or creatinine value \>2 × ULN\]. * Participants with hypersensitivity such as shock after skin test of this study drug. * Participants with uncontrolled severe infection (pneumonia, sepsis, etc). * Participants who received live vaccine or live attenuated vaccine within 6 weeks prior to the first dose of study drug. * Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. * Prior immunosuppressive therapy with lymphocyte-depleting agents/therapies, including both non-B-cell selective and B-cell-depleting agents (e.g., alefacept, alemtuzumab, rituximab). However, participants previously treated with rATG may enroll. * Previous history of stem cell transplantation. * Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of investigational product used in this study (whichever is longer). * Baseline 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (e.g., baseline corrected QT \[QTc\] interval \>450 msec, complete left bundle branch block \[LBBB\], signs of an acute or indeterminate-age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second- or third-degree atrioventricular \[AV\] block, or serious bradyarrhythmias or tachyarrhythmias). If the baseline uncorrected QT interval is \>450 msec, this interval should be rate-corrected using the Fridericia method and the resulting QTcF should be used for decision making and reporting. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or QRS values should be used to determine the participant's eligibility. Computer-interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding participants. * Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Hematologic Response at Week 12 | Week 12 Follow-up Visit | Hematologic response was considered to be effective when 2 or more of the following criteria were met: absolute neutrophil count greater than or equal to (\>=) 500 per microliters, platelet count \>=20,000 per microliters and reticulocyte count \>=60,000 per microliters was observed. In this outcome measure, number of participants with hematologic response classified as effective and not effective were reported. Improvement in counts that were dependent upon exogenously administered growth factors or transfusion, was not considered as fulfilling response criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reticulocyte Count at Day 4, Weeks 1, 2, 4, 6, 8, 10, 12, 24 | Treatment: Day 4; Follow-up: Week 1, 2, 4, 6, 8, 10, 12, 24 | — |
| Number of Participants With Hematologic Response at Week 24 | Week 24 Follow-up Visit | Hematologic response was considered to be effective when 2 or more of the following criteria were met: absolute neutrophil count \>=500 per microliters, platelet count \>=20,000 per microliters and reticulocyte count \>=60,000 per microliters was observed. In this outcome measure, number of participants with hematologic response classified as effective and not effective were reported. Improvement in counts that were dependent upon exogenously administered growth factors or transfusion, was not been considered as fulfilling response criteria. |
| Platelet Count at Day 4, Weeks 1, 2, 4, 6, 8, 10, 12, 24 | Treatment: Day 4; Follow-up: Week 1, 2, 4, 6, 8, 10, 12, 24 | — |
| Number of Participants Who Survived During the Study | Screening (up to 28 days prior to Day 1 of treatment) up to 24 weeks of follow-up (approximately up to 28 weeks) | In this outcome measure, number of participants who survived during the study were observed. |
| Number of Participants With Transfusion Independence at Weeks 12 and 24 | Week 12 Transfusion Independence: Day 1 of Treatment up to Week 12 Follow-up Visit (approximately 12 weeks); Week 24 Transfusion Independence: Day after Week 12 Follow-up visit to Week 24 Follow-up Visit (approximately 12 weeks) | Transfusion independence at Week 12 was defined as when participants did not have any transfusion records from the time of the first dose of the investigational product at Day 1 to the day of Week 12 follow-up visit (inclusive). Transfusion independence at Week 24 was defined as when participants did not have any transfusion records from the day after Week 12 follow-up visit to the day of Week 24 follow-up visit (inclusive). |
| Absolute Neutrophil Count at Day 4, Weeks 1, 2, 4, 6, 8, 10, 12, 24 | Treatment: Day 4; Follow-up: Week 1, 2, 4, 6, 8, 10, 12, 24 | — |
Countries
Japan
Participant flow
Pre-assignment details
Total 3 participants signed the inform consent form (ICF). Out of which 0 participants were screen failures, 3 actually enrolled into the study and assigned to a study treatment.
Participants by arm
| Arm | Count |
|---|---|
| PF-06462700 Participants aged 2 years or \>2 years with moderate and above severity aplastic anemia received PF-06462700 at a dose of 40 mg/kg/day, IV for 4 days. Participants after treatment were followed up for 24 weeks. | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | PF-06462700 |
|---|---|
| Age, Continuous | 29.67 Years STANDARD_DEVIATION 16.56 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 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 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Number of Participants With Hematologic Response at Week 12
Hematologic response was considered to be effective when 2 or more of the following criteria were met: absolute neutrophil count greater than or equal to (\>=) 500 per microliters, platelet count \>=20,000 per microliters and reticulocyte count \>=60,000 per microliters was observed. In this outcome measure, number of participants with hematologic response classified as effective and not effective were reported. Improvement in counts that were dependent upon exogenously administered growth factors or transfusion, was not considered as fulfilling response criteria.
Time frame: Week 12 Follow-up Visit
Population: Full analysis set (FAS) included participants were assigned to investigational product and who took at least 1 dose of investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06462700 | Number of Participants With Hematologic Response at Week 12 | Effective | 2 Participants |
| PF-06462700 | Number of Participants With Hematologic Response at Week 12 | Not Effective | 1 Participants |
Secondary
Absolute Neutrophil Count at Day 4, Weeks 1, 2, 4, 6, 8, 10, 12, 24
Time frame: Treatment: Day 4; Follow-up: Week 1, 2, 4, 6, 8, 10, 12, 24
Population: FAS included participants who were assigned to investigational product and who took at least 1 dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-06462700 | Absolute Neutrophil Count at Day 4, Weeks 1, 2, 4, 6, 8, 10, 12, 24 | NA Neutrophil cells per microliter |
Secondary
Number of Participants Who Survived During the Study
In this outcome measure, number of participants who survived during the study were observed.
Time frame: Screening (up to 28 days prior to Day 1 of treatment) up to 24 weeks of follow-up (approximately up to 28 weeks)
Population: FAS included participants who were assigned to investigational product and who took at least 1 dose of investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-06462700 | Number of Participants Who Survived During the Study | 3 Participants |
Secondary
Number of Participants With Hematologic Response at Week 24
Hematologic response was considered to be effective when 2 or more of the following criteria were met: absolute neutrophil count \>=500 per microliters, platelet count \>=20,000 per microliters and reticulocyte count \>=60,000 per microliters was observed. In this outcome measure, number of participants with hematologic response classified as effective and not effective were reported. Improvement in counts that were dependent upon exogenously administered growth factors or transfusion, was not been considered as fulfilling response criteria.
Time frame: Week 24 Follow-up Visit
Population: FAS included participants who were assigned to investigational product and who took at least 1 dose of investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06462700 | Number of Participants With Hematologic Response at Week 24 | Effective | 2 Participants |
| PF-06462700 | Number of Participants With Hematologic Response at Week 24 | Not Effective | 1 Participants |
Secondary
Number of Participants With Transfusion Independence at Weeks 12 and 24
Transfusion independence at Week 12 was defined as when participants did not have any transfusion records from the time of the first dose of the investigational product at Day 1 to the day of Week 12 follow-up visit (inclusive). Transfusion independence at Week 24 was defined as when participants did not have any transfusion records from the day after Week 12 follow-up visit to the day of Week 24 follow-up visit (inclusive).
Time frame: Week 12 Transfusion Independence: Day 1 of Treatment up to Week 12 Follow-up Visit (approximately 12 weeks); Week 24 Transfusion Independence: Day after Week 12 Follow-up visit to Week 24 Follow-up Visit (approximately 12 weeks)
Population: FAS included participants who were assigned to investigational product and who took at least 1 dose of investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-06462700 | Number of Participants With Transfusion Independence at Weeks 12 and 24 | Week 12 Transfusion Independence | 0 Participants |
| PF-06462700 | Number of Participants With Transfusion Independence at Weeks 12 and 24 | Week 24 Transfusion Independence | 2 Participants |
Secondary
Platelet Count at Day 4, Weeks 1, 2, 4, 6, 8, 10, 12, 24
Time frame: Treatment: Day 4; Follow-up: Week 1, 2, 4, 6, 8, 10, 12, 24
Population: FAS included participants who were assigned to investigational product and who took at least 1 dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-06462700 | Platelet Count at Day 4, Weeks 1, 2, 4, 6, 8, 10, 12, 24 | NA Platelet cells per microliter |
Secondary
Reticulocyte Count at Day 4, Weeks 1, 2, 4, 6, 8, 10, 12, 24
Time frame: Treatment: Day 4; Follow-up: Week 1, 2, 4, 6, 8, 10, 12, 24
Population: FAS included participants who were assigned to investigational product and who took at least 1 dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-06462700 | Reticulocyte Count at Day 4, Weeks 1, 2, 4, 6, 8, 10, 12, 24 | NA Reticulocyte cells per microliter |