A Safety Study of Intravenous Immunoglobulin in Patients With Chronic Immune Thrombocytopenic Purpura (ITP)

• Sponsor: CSL Behring (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01390649
• Collaborator: (none)
• Enrollment: 57
• Locations: 17
• Arm: 1
• Duration (Months): 34
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

It is known that intravenous immunoglobulins can induce hemolysis, but the mechanism is not known in detail. The primary objective of this study was to investigate the specificity of antigens on red blood cells in patients with chronic immune thrombocytopenic purpura (ITP) who have shown signs of clinically relevant hemolysis following treatment with the intravenous immunoglobin Privigen®. The study was to explore potential mechanisms of hemolysis by analysis of the specificity of the antibodies possibly involved. To distinguish between clinically non-relevant hemolysis and a relevant intravascular hemolysis, an independent adjudication by a committee was performed for each patient with signs of hemolysis determined in the laboratory or in the clinic.

This study was requested as a post-marketing commitment study by the United States Food and Drug Administration (FDA). By September 2014, no case of clinically significant intravascular hemolysis was found, and the FDA agreed to halt the study and analyze all hemolysis-relevant endpoints using FDA criteria for hemolysis in addition to analyses planned in the protocol. The study was not restarted.

Condition or Disease	Intervention/Treatment	Phase
Immune Thrombocytopenic Purpura	Biological: IgPro10	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Prospective, Multicenter Study to Investigate the Specificity of in Vivo Antibody Binding to Red Blood Cells in Subjects With Chronic Immune Thrombocytopenic Purpura (ITP) Treated With IgPro10 (Privigen®) Who Have Shown Signs of Hemolysis
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IgPro10	Biological: IgPro10; IgPro10 will be administrated by IV infusion either a single dose of 1 g/kg bw on 1 day or 2 doses of 1 g/kg bw on 2 days (2 g/kg bw total dose) dependent on the response to the first treatment.; Other Names: Privigen

Outcome Measures

Primary Outcome Measures

1. Set of Antibodies Most Frequently Bound to Red Blood Cells (RBCs) in Subjects Experiencing Clinically Significant Intravascular Hemolysis [Within 3 days of infusion]

   The occurrence of clinically significant intravascular hemolysis was determined by an independent Adjudication Committee. No subject experienced clinically significant intravascular hemolysis; therefore, the primary safety endpoint could not be analyzed.

Secondary Outcome Measures

1. Responder Rate [Within 6 days after the first infusion]

   The responder rate is the percentage of subjects who have a platelet response (defined as a platelet count increase at least once to ≥ 50 x 10^9/L after the first IgPro10 administration).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of chronic ITP

• Age of 18 to 65 years

• Platelet count of ≤ 30 x 10^9/L at screening

Exclusion Criteria:

• Planned splenectomy throughout the study period

• Treatment with immunoglobulin G for intravenous administration (IVIG) or anti-D immunoglobulin within 3 weeks prior to screening

• Use of drugs that have any pharmacological effect on the blood clotting system within 3 weeks prior to screening

• Known allergy or other severe reactions to blood products including intolerability to previous IVIG

• Known hyperprolinemia

• Red blood cell transfusion or erythropoietin treatment within the last 14 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UMHAT "Dr. Georgi Stranski" Clinic of Haematology	Pleven		Bulgaria
2	UMHAT "Sv. Georgi" Clinic of Haematology	Plovdiv		Bulgaria
3	Tokuda Hospital	Sofia		Bulgaria
4	Emergency Clinical County Hospital Baia Mare	Baia Mare		Romania
5	Emergency Clinical County Hospital Brasov	Brasov		Romania
6	Clinical Institute "Fundeni"	Bucharest		Romania
7	Universitary Hospital	Bucharest		Romania
8	Clinical City Hospital "Filantropia"	Craiova		Romania
9	City Hospital Oradea	Oradea		Romania
10	Emergency Clinical County Hospital Tg. Mures	Tg. Mures		Romania
11	Emergency Clinical City Hospital Timisoara	Timisoara		Romania
12	Oncomed SRL	Timisoara		Romania
13	Salvo-San-Ciobanca SRL	Zalau		Romania
14	Clinical Center of Serbia	Belgrade		Serbia
15	Clinical Hospital Bezanijska Kosa	Belgrade		Serbia
16	Clinical Hospital Zemun	Belgrade		Serbia
17	Clinical Center Nis	Nis		Serbia

Sponsors and Collaborators

• CSL Behring

Investigators

• Principal Investigator: Wieslaw Jedrzejczak, Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: CSL Behring
• ClinicalTrials.gov Identifier: NCT01390649
• Other Study ID Numbers: IgPro10_4001; 2011-000263-27
• First Posted: Jul 11, 2011
• Last Update Posted: Apr 8, 2016
• Last Verified: Sep 1, 2015

• Keywords provided by CSL Behring: ITP
• Additional relevant MeSH terms: Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic; Immunoglobulins, Intravenous

Study Results

Participant Flow

Pre-assignment Detail	Screening occurred within 6 days before treatment with IgPro10 (Privigen). Subjects who met all of the inclusion criteria and none of the exclusion criteria could be enrolled into the study. Of 58 eligible subjects, one withdrew consent before treatment and 57 subjects received at least 1 dose of Privigen.

Arm/Group Title	IgPro10
Arm/Group Description	IgPro10 was administered by IV infusion either as a single dose of 1 g/kg bw on 1 day or 2 doses of 1 g/kg bw on 2 days (2 g/kg bw total dose) dependent on the response to the first IgPro10 dose.
Period Title: Overall Study
STARTED	57
COMPLETED	56
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	IgPro10
Arm/Group Description	IgPro10 was administered by IV infusion either as a single dose of 1 g/kg bw on 1 day or 2 doses of 1 g/kg bw on 2 days (2 g/kg bw total dose) dependent on the response to the first IgPro10 dose.
Overall Participants	57
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	55 96.5%
>=65 years	2 3.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.5 (13.10)
Sex: Female, Male (Count of Participants)
Female	37 64.9%
Male	20 35.1%

Outcome Measures

1. Primary Outcome

Title	Set of Antibodies Most Frequently Bound to Red Blood Cells (RBCs) in Subjects Experiencing Clinically Significant Intravascular Hemolysis
Description	The occurrence of clinically significant intravascular hemolysis was determined by an independent Adjudication Committee. No subject experienced clinically significant intravascular hemolysis; therefore, the primary safety endpoint could not be analyzed.
Time Frame	Within 3 days of infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IgPro10
Arm/Group Description	IgPro10 was administered by IV infusion either as a single dose of 1 g/kg bw on 1 day or 2 doses of 1 g/kg bw on 2 days (2 g/kg bw total dose) dependent on the response to the first IgPro10 dose.
Measure Participants	0

2. Secondary Outcome

Title	Responder Rate
Description	The responder rate is the percentage of subjects who have a platelet response (defined as a platelet count increase at least once to ≥ 50 x 10^9/L after the first IgPro10 administration).
Time Frame	Within 6 days after the first infusion

Outcome Measure Data

Analysis Population Description

Full analysis set: all subjects who received at least 1 IgPro10 infusion.

Arm/Group Title	IgPro10
Arm/Group Description	IgPro10 was administered by IV infusion either as a single dose of 1 g/kg bw on 1 day or 2 doses of 1 g/kg bw on 2 days (2 g/kg bw total dose) dependent on the response to the first IgPro10 dose.
Measure Participants	57
Number (95% Confidence Interval) [percentage of participants]	74 129.8%

Adverse Events

Time Frame	For the duration of individual subject participation in the study, up to approximately 35 days.
Arm/Group Title	IgPro10
Arm/Group Description	IgPro10 was administered by IV infusion either as a single dose of 1 g/kg bw on 1 day or 2 doses of 1 g/kg bw on 2 days (2 g/kg bw total dose) dependent on the response to the first IgPro10 dose.
All Cause Mortality
	IgPro10
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	IgPro10
	Affected / at Risk (%)	# Events
Total	1/57 (1.8%)
Blood and lymphatic system disorders
Immune Thrombocytopenic Purpura	1/57 (1.8%)	1
Other (Not Including Serious) Adverse Events
	IgPro10
	Affected / at Risk (%)	# Events
Total	19/57 (33.3%)
General disorders
Pyrexia	3/57 (5.3%)	6
Nervous system disorders
Headache	17/57 (29.8%)	23

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

CSL agreements and restrictions on publishing may vary with individual investigators; however, CSL will not prohibit any investigator from publishing. CSL supports the publication of results from all centers of a multi-center trial and generally requires that reports based on single-site data not precede the primary publication of the entire clinical trial.