Immune (Idiopathic) Thrombocytopenic Purpura
Conditions
Brief summary
The purpose of this study is to determine whether IGIV3I Grifols 10% is effective in the treatment of immune thrombocytopenic purpura.
Detailed description
To determine if IGIV3I Grifols 10% is a consistently effective treatment in patients diagnosed with immune thrombocytopenic purpura with respect to: 1. Increase of platelet count ≥ 50x10\^9/L (primary objective). 2. Time taken for the platelet count to reach ≥ 50x10\^9/L. 3. The length of time the platelet count remains ≥ 50x10\^9/L. 4. The maximum platelet level. 5. Regression of bleeding episodes during the first 10 or 14 days. To determine if IGIV3I Grifols 10% is safe with respect to: Nature, severity and frequency of adverse reactions during and after infusions by percentage of subjects and percentage of infusions.
Interventions
BIOLOGICALIGIV3I Grifols
Immune Globulin Intravenous (Human)
Sponsors
Instituto Grifols, S.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 82 Years
Healthy volunteers
No
Inclusion criteria
1. Be aged between 18 and 82 at the time of written consent. 2. Have confirmed diagnosis of chronic ITP and fulfil all the following criteria: * irrelevant history except for the symptoms of bleeding, * pattern of bleedings associated with platelet disorders, * physical examination irrelevant for the ITP, except for the signs of bleeding, * isolated thrombocytopenia in the blood count; apart from thrombocytopenia, the blood count is normal for the patient's age, or if abnormal, readily explained, * peripheral blood smear consistent with ITP: thrombocytopenia with platelets of normal size or slightly larger than normal, with absence of platelet clumps and giant platelets; normal red blood cell and white blood cell morphology, * confirmed diagnosis of immune thrombocytopenic purpura or, when any abnormal finding is present, additional diagnostic evaluation excludes other causes of thrombocytopenia. * Previous known diagnosis of ITP for at least 3 months. 3. To show a platelet count platelet count ≤ 20x10\^9/L at the moment of the first infusion with the study product. 4. Have read the patient information and consent sheet, agreed to participate in the trial, and signed the consent sheet. 5. Be expected to receive treatment over 5 days and follow-up for 3 months. 6. For women of childbearing age, use adequate contraceptive method such as oral contraceptives, intrauterine device or tubal ligation during one-month period after the first infusion in the study.
Exclusion criteria
1. Have immune thrombocytopenia secondary to other pathologies or drug mediated thrombocytopenia. 2. Have a known diagnosis of other autoimmune diseases, established in the medical history and laboratory findings with positive results for the determination of antinuclear antibodies, anti-cardiolipin antibodies, lupus anticoagulant or direct Coombs test. 3. Present important active bleeding due to other reasons apart from the ITP. 4. Exhibit an identifiable alternative cause of their thrombocytopenia, such as splenomegaly, family thrombocytopenia, bacteraemia, sepsis or active infection requiring or not therapy. 5. Are presenting renal dysfunction. 6. Have non-controlled arterial hypertension. 7. Have documented liver cirrhosis or any hepatic disorder with alanine aminotransferase (ALT) levels 2.5 times or more than the normal upper limit or bilirubin greater than 2 mg/dL. 8. Are presenting a cardiac disease including a history of coronary artery disease, angina pectoris or congestive heart failure. 9. Present known infection due to HIV or hepatitis C virus (HCV). 10. Have been previously treated with IVIG or anti-D immunoglobulin being unresponsive. 11. Have a history of serious adverse reactions or non-serious but frequent adverse reactions to intravenous immune globulin (IVIG) preparations or other products derived from blood. 12. Have known allergies to any IGIV3I Grifols components, such as D-sorbitol. 13. Are simultaneously participating in other clinical studies or have received an investigational drug in the 3 months prior to the start of the study. 14. Have been involved in the present study and being treated with the formulation at 5% (IGIV3I Grifols 5%). 15. Have conditions that might affect patient compliance. 16. Are unable to provide a storage serum sample just before the first dose of IGIV3I Grifols. 17. Are pregnant or nursing an infant child or unwilling to practice adequate birth control in 1-month period after the first infusion in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Responder Patients | At any time during the study period (The platelet count was measured at Days 1-6, 10, 14. 21, 30, 60, 90). | The primary efficacy endpoint was the proportion of patients who reached a platelet count ≥ 50x10\^9/L. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Platelet Count ≥ 50x10^9/L (≤ Days) | At any time during the study period (time points: Days 1-6, 10, 14, 21, 30, 60, 90 post-first infusion day [Day 1]) | The time taken for the platelet count to reach ≥ 50x10\^9/L from first dose |
| Length of Time Platelet Count Remains ≥ 50x10^9/L (≥ Days) | At any time during the study period (up to 3 months [90 days]) | Length of time platelet count remained ≥ 50x10\^9/L from first dose (Day 1) |
| Regression of Hemorrhages. | First 10 to14 days since the first infusion day (Day 1) | Percentage of subjects with regression of hemorrhages of Types 1 to 3: * Type 0: Patients without symptoms of bleeding at the first infusion continue without presenting spontaneous bleeding * Type 1: Patients with bleeding symptoms at the first infusion had a reduction of the size of large ecchymoses, and no spontaneous appearance of new ecchymoses * Type 2: Patients with bleeding symptoms at the first infusion had a decrease in the number of cutaneous petechiae, or the extent of the affected area of the body decreased * Type 3: Patients had active mucosal bleedings at the first infusion, these episodes stopped without re-bleeding, and there was no occurrence of new spontaneous mucosal hemorrhages (e.g., gingival bleeding, epistaxis) |
| Maximum Platelet Level Reached During the Follow-up Period | During the follow-up period (time points: Days 6, 10, 14, 21, 30, 60, 90 post-first infusion day [Day 1]) | Platelet count was measured at various time points in the follow-up period after infusion. |
| Frequency of Adverse Reactions During and After Infusions by Percentage of Infusions | At any time during the study period (from patient's signature of the informed consent form until 3 months of follow-up) | All adverse events (AEs) are tabulated and summarized. The incidence, severity, and causal relationship of the AEs to IGIV3I Grifols are presented by system organ class after medical coding according to the version 15.0 of Medical Dictionary for Regulatory Activities (MedDRA). The frequency of infusions associated with at least one AE and adverse drug reactions are estimated. |
| Changes in Vital Signs and Clinically Relevant Changes in Laboratory Parameters After the Infusions, Including Renal Function (Creatinine Levels) | At any time during the study period (from patient's signature of the informed consent form until 3 months of follow-up) | Laboratory parameters at each treatment day and visit are summarized by patient. Results were marked as normal/abnormal (whether the result is below, within or above the respective reference range) and relevant/irrelevant (as determined by the investigator). The number of abnormal values considered clinically relevant changes (based on the investigator's judgment) was listed. |
| Viral Safety Through the Investigation of Patients Virology Status (Hepatitis A Virus [HA | At any time during the study period (from patient's signature of the informed consent form until 3 months of follow-up) | The results of HIV-1 and -2 antibodies, HCV antibody, HBsAg, HBV antibodies, HAV antibodies, HIV nucleic acid amplification test \[NAT\], and HCV NAT on Day 1, Day 14, and at Month 1, Month 2 and Month 3 were recorded for several of these markers (as appropriate). A comparison of negative viral markers on Day 1 and Month 3 was performed |
| Frequency of Adverse Reactions During and After Infusions by Percentage of Patients | At any time during the study period (from patient's signature of the informed consent form until 3 months of follow-up) | All adverse events (AEs) are tabulated and summarized. The incidence, severity, and causal relationship of the AEs to IGIV3I Grifols are presented by system organ class after medical coding according to the version 15.0 of Medical Dictionary for Regulatory Activities (MedDRA). The frequency of patients with at least one AE and adverse drug reactions are estimated. |
Countries
Russia, Spain, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1 Treatment Group With IGIV3I Open label, non-randomized treatment group with IGIV3I Grifols
IGIV3I Grifols: Immune Globulin Intravenous (Human)
Each patient received a total dose of 2 g/kg IGIV3I Grifols, given intravenously over either 2 days or 5 days in divided doses. | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | 1 Treatment Group With IGIV3I |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 43 years |
| Platelet count | 8.5 platelets x 10^-9/L |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 18 Participants |
| Region of Enrollment Russian Federation | 12 participants |
| Region of Enrollment Spain | 4 participants |
| Region of Enrollment United Kingdom | 2 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 6 Participants |
| Subjects with haemorrhagic history No | 5 participants |
| Subjects with haemorrhagic history Yes | 13 participants |
| Subjects with medical history of splenectomy No | 9 participants |
| Subjects with medical history of splenectomy Yes | 9 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 18 |
| serious Total, serious adverse events | 2 / 18 |
Outcome results
Primary
Responder Patients
The primary efficacy endpoint was the proportion of patients who reached a platelet count ≥ 50x10\^9/L.
Time frame: At any time during the study period (The platelet count was measured at Days 1-6, 10, 14. 21, 30, 60, 90).
Population: All 18 subjects received at least one infusion (at any dose) of IGIV3I Grifols and were included in the intent-to-treat (ITT) population for efficacy and safety analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1 Treatment Group With IGIV3I | Responder Patients | 72.2 percentage of subjects |
Secondary
Changes in Vital Signs and Clinically Relevant Changes in Laboratory Parameters After the Infusions, Including Renal Function (Creatinine Levels)
Laboratory parameters at each treatment day and visit are summarized by patient. Results were marked as normal/abnormal (whether the result is below, within or above the respective reference range) and relevant/irrelevant (as determined by the investigator). The number of abnormal values considered clinically relevant changes (based on the investigator's judgment) was listed.
Time frame: At any time during the study period (from patient's signature of the informed consent form until 3 months of follow-up)
Population: Intent-to-treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1 Treatment Group With IGIV3I | Changes in Vital Signs and Clinically Relevant Changes in Laboratory Parameters After the Infusions, Including Renal Function (Creatinine Levels) | Clinically relevant changes in vital signs | 0 participants |
| 1 Treatment Group With IGIV3I | Changes in Vital Signs and Clinically Relevant Changes in Laboratory Parameters After the Infusions, Including Renal Function (Creatinine Levels) | Clinically relevant changes in lab parameters | 7 participants |
Secondary
Frequency of Adverse Reactions During and After Infusions by Percentage of Infusions
All adverse events (AEs) are tabulated and summarized. The incidence, severity, and causal relationship of the AEs to IGIV3I Grifols are presented by system organ class after medical coding according to the version 15.0 of Medical Dictionary for Regulatory Activities (MedDRA). The frequency of infusions associated with at least one AE and adverse drug reactions are estimated.
Time frame: At any time during the study period (from patient's signature of the informed consent form until 3 months of follow-up)
Population: ITT population: patient who received at least one infusion with the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1 Treatment Group With IGIV3I | Frequency of Adverse Reactions During and After Infusions by Percentage of Infusions | Frequency of infusions with adverse events | 26.3 percentage of infusions |
| 1 Treatment Group With IGIV3I | Frequency of Adverse Reactions During and After Infusions by Percentage of Infusions | Frequency of infusions with adverse drug reactions | 24.6 percentage of infusions |
Secondary
Frequency of Adverse Reactions During and After Infusions by Percentage of Patients
All adverse events (AEs) are tabulated and summarized. The incidence, severity, and causal relationship of the AEs to IGIV3I Grifols are presented by system organ class after medical coding according to the version 15.0 of Medical Dictionary for Regulatory Activities (MedDRA). The frequency of patients with at least one AE and adverse drug reactions are estimated.
Time frame: At any time during the study period (from patient's signature of the informed consent form until 3 months of follow-up)
Population: ITT population: patient who received one infusion with the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 1 Treatment Group With IGIV3I | Frequency of Adverse Reactions During and After Infusions by Percentage of Patients | Frequency of patients with AEs | 88.9 percentage of patients |
| 1 Treatment Group With IGIV3I | Frequency of Adverse Reactions During and After Infusions by Percentage of Patients | Frequency of patients with adverse drug reactions | 38.9 percentage of patients |
Secondary
Length of Time Platelet Count Remains ≥ 50x10^9/L (≥ Days)
Length of time platelet count remained ≥ 50x10\^9/L from first dose (Day 1)
Time frame: At any time during the study period (up to 3 months [90 days])
Population: From all 18 subjects who received at least one infusion and were included in the intent-to-treat (ITT) population only 13 responded to the treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1 Treatment Group With IGIV3I | Length of Time Platelet Count Remains ≥ 50x10^9/L (≥ Days) | 9 days |
Secondary
Maximum Platelet Level Reached During the Follow-up Period
Platelet count was measured at various time points in the follow-up period after infusion.
Time frame: During the follow-up period (time points: Days 6, 10, 14, 21, 30, 60, 90 post-first infusion day [Day 1])
Population: The maximum platelet counts were taken from the population who responded to treatment (platelet count ≥ 50x10\^9/L). If any patient received banned medication due to ITP progression during the study, the values obtained after patients received treatment were excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1 Treatment Group With IGIV3I | Maximum Platelet Level Reached During the Follow-up Period | 146.0 platelets x 10^-9/L |
Secondary
Regression of Hemorrhages.
Percentage of subjects with regression of hemorrhages of Types 1 to 3: * Type 0: Patients without symptoms of bleeding at the first infusion continue without presenting spontaneous bleeding * Type 1: Patients with bleeding symptoms at the first infusion had a reduction of the size of large ecchymoses, and no spontaneous appearance of new ecchymoses * Type 2: Patients with bleeding symptoms at the first infusion had a decrease in the number of cutaneous petechiae, or the extent of the affected area of the body decreased * Type 3: Patients had active mucosal bleedings at the first infusion, these episodes stopped without re-bleeding, and there was no occurrence of new spontaneous mucosal hemorrhages (e.g., gingival bleeding, epistaxis)
Time frame: First 10 to14 days since the first infusion day (Day 1)
Population: ITT population: patients who received at least one infusion of the study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1 Treatment Group With IGIV3I | Regression of Hemorrhages. | 83.3 percentage of subjects |
Secondary
Time to Reach Platelet Count ≥ 50x10^9/L (≤ Days)
The time taken for the platelet count to reach ≥ 50x10\^9/L from first dose
Time frame: At any time during the study period (time points: Days 1-6, 10, 14, 21, 30, 60, 90 post-first infusion day [Day 1])
Population: From all 18 subjects who received at least one infusion and were included in the intent-to-treat (ITT) population but only 13 responded to the treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1 Treatment Group With IGIV3I | Time to Reach Platelet Count ≥ 50x10^9/L (≤ Days) | 2 days |
Secondary
Viral Safety Through the Investigation of Patients Virology Status (Hepatitis A Virus [HA
The results of HIV-1 and -2 antibodies, HCV antibody, HBsAg, HBV antibodies, HAV antibodies, HIV nucleic acid amplification test \[NAT\], and HCV NAT on Day 1, Day 14, and at Month 1, Month 2 and Month 3 were recorded for several of these markers (as appropriate). A comparison of negative viral markers on Day 1 and Month 3 was performed
Time frame: At any time during the study period (from patient's signature of the informed consent form until 3 months of follow-up)
Population: Intent-to-treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1 Treatment Group With IGIV3I | Viral Safety Through the Investigation of Patients Virology Status (Hepatitis A Virus [HA | 0 seroconversions |