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Clinical Trial in Patients Diagnosed With Immune Thrombocytopenic Purpura (ITP)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Grifols Biologicals Inc. ( Instituto Grifols, S.A. )
ClinicalTrials.gov Identifier:
NCT00699140
First received: June 16, 2008
Last updated: January 9, 2016
Last verified: January 2016
  Purpose
The purpose of this study is to determine whether IGIV3I Grifols 10% is effective in the treatment of immune thrombocytopenic purpura.

Condition Intervention Phase
Immune (Idiopathic) Thrombocytopenic Purpura
Biological: IGIV3I Grifols
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clinical Trial to Evaluate the Efficacy and the Safety of IGIV3I Grifols 10% (Human Intravenous Immunoglobulin) in Patients Diagnosed With Immune Thrombocytopenic Purpura

Resource links provided by NLM:


Further study details as provided by Grifols Biologicals Inc.:

Primary Outcome Measures:
  • Responder Patients [ Time Frame: At any time during the study period (The platelet count was measured at Days 1-6, 10, 14. 21, 30, 60, 90). ] [ Designated as safety issue: No ]
    The primary efficacy endpoint was the proportion of patients who reached a platelet count ≥ 50x10^9/L.


Secondary Outcome Measures:
  • Maximum Platelet Level Reached During the Follow-up Period [ Time Frame: During the follow-up period (time points: Days 6, 10, 14, 21, 30, 60, 90 post-first infusion day [Day 1]) ] [ Designated as safety issue: No ]
    Platelet count was measured at various time points in the follow-up period after infusion.

  • Time to Reach Platelet Count ≥ 50x10^9/L (≤ Days) [ 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]) ] [ Designated as safety issue: No ]
    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) [ Time Frame: At any time during the study period (up to 3 months [90 days]) ] [ Designated as safety issue: No ]
    Length of time platelet count remained ≥ 50x10^9/L from first dose (Day 1)

  • Regression of Hemorrhages. [ Time Frame: First 10 to14 days since the first infusion day (Day 1) ] [ Designated as safety issue: Yes ]

    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)

  • Frequency of Adverse Reactions During and After Infusions by Percentage of Patients [ Time Frame: At any time during the study period (from patient's signature of the informed consent form until 3 months of follow-up) ] [ Designated as safety issue: Yes ]
    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.

  • Frequency of Adverse Reactions During and After Infusions by Percentage of Infusions [ Time Frame: At any time during the study period (from patient's signature of the informed consent form until 3 months of follow-up) ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: At any time during the study period (from patient's signature of the informed consent form until 3 months of follow-up) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: At any time during the study period (from patient's signature of the informed consent form until 3 months of follow-up) ] [ Designated as safety issue: Yes ]
    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


Enrollment: 18
Study Start Date: February 2008
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 treatment group with IGIV3I Grifols

Open label, non-randomized treatment group with IGIV3I Grifols

Each patient received a total dose of 2 g/kg IGIV3I Grifols, given intravenously over either 2 days or 5 days in divided doses.

Biological: IGIV3I Grifols
Immune Globulin Intravenous (Human)
Other Name: IGIV

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.

  Eligibility

Ages Eligible for Study:   18 Years to 82 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00699140

Locations
Russian Federation
Federal Research Clinical Centre of Pediatric Hematology, Oncology and Immunology Roszdrava
Moscow, Russian Federation
Haematology Research Centre of Russian Academy of Medical Science
Moscow, Russian Federation
Spain
Hospital General Vall d´Hebron
Barcelona, Spain
. Hospital de León
Leon, Spain
Hospital General Universitario La Paz
Madrid, Spain
Hospital Universitario La Fe
Valencia, Spain
United Kingdom
Hillingdon Hospital
Middlesex, United Kingdom, UB8 3NN
Sponsors and Collaborators
Instituto Grifols, S.A.
Investigators
Principal Investigator: María Teresa Álvarez, MD Hospital General Universitario La Paz
  More Information

Responsible Party: Instituto Grifols, S.A.
ClinicalTrials.gov Identifier: NCT00699140     History of Changes
Other Study ID Numbers: IG202 
Study First Received: June 16, 2008
Results First Received: June 16, 2015
Last Updated: January 9, 2016
Health Authority: Russia: Ministry of Health of the Russian Federation
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Purpura, Thrombocytopenic
Purpura
Purpura, Thrombocytopenic, Idiopathic
Blood Coagulation Disorders
Hematologic Diseases
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders
Immune System Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Hemorrhagic Disorders
Autoimmune Diseases
Immunoglobulins, Intravenous
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 06, 2016