Efficacy and Safety of Immunoglobulin Intravenous (Human) 10% (NewGam) in Primary Immune Thrombocytopenia

• Sponsor: Octapharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01349790
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arm: 1
• Duration (Months): 21
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

NewGam is a newly developed human normal immunoglobulin solution for intravenous administration (IGIV). This study will evaluate the safety and efficacy of NewGam 10% in patients with primary immune thrombocytopenia.

Condition or Disease	Intervention/Treatment	Phase
Primary Thrombocytopenia	Drug: NewGam	Phase 3

Detailed Description

The primary objective of the study is to assess the efficacy of NewGam in correcting the platelet count. The secondary objective of the study is to evaluate the safety of NewGam. Safety will be assessed by monitoring vital signs, physical examination, evaluation of adverse events (AE) and laboratory parameters, and viral safety testing.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prospective, Open-label, Non-controlled, Multicenter, Phase III Clinical Study to Evaluate the Efficacy and Safety of Immunoglobulin Intravenous (Human) 10% (NewGam) in Primary Immune Thrombocytopenia
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NewGam Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.	Drug: NewGam; NewGam is a solution of human normal immunoglobulin 10% treated with solvent/detergent and nanofiltered for intravenous administration.

Outcome Measures

Primary Outcome Measures

1. Percentage of Responders [Day 1 to Day 8]

   A responder is a study participant with an increase in platelets to ≥ 50x10^9/L within 7 days after the first infusion, ie, by study Day 8.

Secondary Outcome Measures

1. Percentage of Alternative Responders [Day 1 to Day 22]

   An alternative responder is a study participant with an increase in platelets to ≥ 30x10^9/L and to at least double the baseline platelet count, confirmed on at least 2 occasions at least 7 days apart, and absence of bleeding.

2. Percentage of Complete Responders [Day 1 to Day 22]

   A complete responder is a study participant with an increase in platelets to ≥ 100x10^9/L, confirmed on at least 2 occasions at least 7 days apart, and absence of bleeding.

3. Percentage of Alternative Responders Who Lost the Response [Day 1 to Day 22]

   An alternative responder who lost the response is a study participant who met the criterion for an alternative response but who then deteriorated, ie, their platelet count decreased to < 30x10^9/L, their platelet count decreased to less than double the baseline count, or bleeding occurred.

4. Percentage of Complete Responders Who Lost the Response [Day 1 to Day 22]

   A complete responder who lost the response is a study participant who met the criterion for a complete response but who then deteriorated, ie, their platelet count decreased to < 100x10^9/L or bleeding occurred.

5. Time to a Response [Day 1 to Day 8]

   A study participant had a response if their platelets increased to ≥ 50x10^9/L within 7 days after the first infusion, ie, by study Day 8.

6. Time to an Alternative Response [Day 1 to Day 22]

   A study participant had a response if their platelets increased to ≥ 30x10^9/L and to at least double the baseline platelet count, confirmed on at least 2 occasions at least 7 days apart, and absence of bleeding.

7. Time to a Complete Response [Day 1 to Day 22]

   A study participant had a complete response if their platelets increased to ≥ 100x10^9/L, confirmed on at least 2 occasions at least 7 days apart, and absence of bleeding.

8. Duration of a Response [Day 1 to Day 22]

   The duration of a response was defined as the time from when a response was achieved until the platelet count fell below 50x10^9/L.

9. Duration of an Alternative Response [Day 1 to Day 22]

   The duration of an alternative response was defined as the time from when an alternative response was achieved until the platelet count fell below 50x10^9/L.

10. Duration of a Complete Response [Day 1 to Day 22]

    The duration of a complete response was defined as the time from when a complete response was achieved until the platelet count fell below 50x10^9/L.

11. Platelet Count by Visit [Day 1 to Day 22]

    The platelet count at each study visit are presented.

12. Maximum Platelet Count [Day 1 to Day 22]

    The maximum platelet count achieved during the study is presented.

13. Percentage of Responders Who Achieved a Normal Platelet Count [Day 1 to Day 22]

    The percentage of responders who achieved a normal platelet count is presented.

14. Bleeding Intensity [Day 1 to Day 22]

    The percentage of participants with various intensities of overall bleeding, epistaxis (bleeding of the nose), oral bleeding, and skin bleeding graded as none, minor, mild, moderate, or severe at Baseline and Day 22 are reported.

15. Percentage of Participants Who Achieved a Platelet Count > 30x10^9/L [Day 1 to Day 2]

    The percentage of participants who achieved a platelet count > 30x10^9/L within 1 and 2 days after infusion is reported.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Age of ≥ 18 and ≤ 65 years.

2. Confirmed diagnosis of chronic primary immune thrombocytopenia (ITP) (diagnosed with a threshold platelet count < 100x10^9/L) of at least 12 months duration.

3. Platelet count of no more than 20x10^9/L with or without bleeding manifestations.

4. Freely given written informed consent from patient.

5. Women of childbearing potential must have a negative result on a pregnancy test (human chorionic gonadotropin [HCG]-based assay) and need to practice contraception using a method of proven reliability for the duration of the study.

Exclusion Criteria:

1. Thrombocytopenia secondary to other diseases (such as acquired immunodeficiency syndrome [AIDS] or systemic lupus erythematosus [SLE]), or drug-related thrombocytopenia.

2. Administration of intravenous immunoglobulin (IGIV), anti-D immunoglobulin or thrombopoietin receptor agonists, or other platelet enhancing drugs (including immunosuppressive or other immunomodulatory drugs) within 3 weeks before enrollment, except for:

• Long-term corticosteroid therapy when the dose has been stable during the preceding 3 weeks and no dosage change is planned until study Day 22.

• Long-term azathioprine, cyclophosphamide, or attenuated androgen therapy when the dose has been stable during the preceding 3 months and no dosage change is planned until study Day 22.

1. Unresponsive to previous treatment with IGIV or anti-D immunoglobulin.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Abdulgabar Salama	Berlin		Germany

Sponsors and Collaborators

• Octapharma

Investigators

• Principal Investigator: Abdulgabar Salama, MD, Universitätsklinikum Charite, Med. Fakultät der Humboldt-Universität Berlin
• Study Director: Wolfgang Frenzel, MD, Octapharma AG

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Octapharma
• ClinicalTrials.gov Identifier: NCT01349790
• Other Study ID Numbers: NGAM-02; 2009-014589-24
• First Posted: May 9, 2011
• Last Update Posted: Jun 7, 2017
• Last Verified: May 1, 2017

• Keywords provided by Octapharma: ITP; Primary immune thrombocytopenia
• Additional relevant MeSH terms: Thrombocytopenia; Purpura, Thrombocytopenic, Idiopathic

Study Results

Participant Flow

Arm/Group Title	NewGam
Arm/Group Description	Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.
Period Title: Overall Study
STARTED	40
COMPLETED	31
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	NewGam
Arm/Group Description	Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.
Overall Participants	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.7 (15.34)
Sex: Female, Male (Count of Participants)
Female	17 42.5%
Male	23 57.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Responders
Description	A responder is a study participant with an increase in platelets to ≥ 50x10^9/L within 7 days after the first infusion, ie, by study Day 8.
Time Frame	Day 1 to Day 8

Outcome Measure Data

Analysis Population Description

Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam and who had at least 1 post-baseline measurement of platelet concentration.

Arm/Group Title	NewGam
Arm/Group Description	Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.
Measure Participants	36
Number (95% Confidence Interval) [Percentage of participants]	80.6 201.5%

2. Secondary Outcome

Title	Percentage of Alternative Responders
Description	An alternative responder is a study participant with an increase in platelets to ≥ 30x10^9/L and to at least double the baseline platelet count, confirmed on at least 2 occasions at least 7 days apart, and absence of bleeding.
Time Frame	Day 1 to Day 22

Outcome Measure Data

Analysis Population Description

Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam and who had at least 1 post-baseline measurement of platelet concentration.

Arm/Group Title	NewGam
Arm/Group Description	Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.
Measure Participants	36
Number (95% Confidence Interval) [Percentage of participants]	66.7 166.8%

3. Secondary Outcome

Title	Percentage of Complete Responders
Description	A complete responder is a study participant with an increase in platelets to ≥ 100x10^9/L, confirmed on at least 2 occasions at least 7 days apart, and absence of bleeding.
Time Frame	Day 1 to Day 22

Outcome Measure Data

Analysis Population Description

Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam and who had at least 1 post-baseline measurement of platelet concentration.

Arm/Group Title	NewGam
Arm/Group Description	Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.
Measure Participants	36
Number (95% Confidence Interval) [Percentage of participants]	50.0 125%

4. Secondary Outcome

Title	Percentage of Alternative Responders Who Lost the Response
Description	An alternative responder who lost the response is a study participant who met the criterion for an alternative response but who then deteriorated, ie, their platelet count decreased to < 30x10^9/L, their platelet count decreased to less than double the baseline count, or bleeding occurred.
Time Frame	Day 1 to Day 22

Outcome Measure Data

Analysis Population Description

Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam and who had at least 1 post-baseline measurement of platelet concentration. Only participants with an alternative response were included in the analysis.

Arm/Group Title	NewGam
Arm/Group Description	Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.
Measure Participants	24
Number (95% Confidence Interval) [Percentage of participants]	45.8 114.5%

5. Secondary Outcome

Title	Percentage of Complete Responders Who Lost the Response
Description	A complete responder who lost the response is a study participant who met the criterion for a complete response but who then deteriorated, ie, their platelet count decreased to < 100x10^9/L or bleeding occurred.
Time Frame	Day 1 to Day 22

Outcome Measure Data

Analysis Population Description

Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam and who had at least 1 post-baseline measurement of platelet concentration. Only participants with a complete response were included in the analysis.

Arm/Group Title	NewGam
Arm/Group Description	Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.
Measure Participants	18
Number (95% Confidence Interval) [Percentage of participants]	77.8 194.5%

6. Secondary Outcome

Title	Time to a Response
Description	A study participant had a response if their platelets increased to ≥ 50x10^9/L within 7 days after the first infusion, ie, by study Day 8.
Time Frame	Day 1 to Day 8

Outcome Measure Data

Analysis Population Description

Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration. Only responders were included in the analysis.

Arm/Group Title	NewGam
Arm/Group Description	Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.
Measure Participants	29
Median (95% Confidence Interval) [Days]	2.0

7. Secondary Outcome

Title	Time to an Alternative Response
Description	A study participant had a response if their platelets increased to ≥ 30x10^9/L and to at least double the baseline platelet count, confirmed on at least 2 occasions at least 7 days apart, and absence of bleeding.
Time Frame	Day 1 to Day 22

Outcome Measure Data

Analysis Population Description

Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration. Only participants with an alternative response were included in the analysis.

Arm/Group Title	NewGam
Arm/Group Description	Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.
Measure Participants	24
Median (95% Confidence Interval) [Days]	1.0

8. Secondary Outcome

Title	Time to a Complete Response
Description	A study participant had a complete response if their platelets increased to ≥ 100x10^9/L, confirmed on at least 2 occasions at least 7 days apart, and absence of bleeding.
Time Frame	Day 1 to Day 22

Outcome Measure Data

Analysis Population Description

Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration. Only participants with a complete response were included in the analysis.

Arm/Group Title	NewGam
Arm/Group Description	Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.
Measure Participants	18
Median (95% Confidence Interval) [Days]	2.0

9. Secondary Outcome

Title	Duration of a Response
Description	The duration of a response was defined as the time from when a response was achieved until the platelet count fell below 50x10^9/L.
Time Frame	Day 1 to Day 22

Outcome Measure Data

Analysis Population Description

Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration. Only responders were included in the analysis.

Arm/Group Title	NewGam
Arm/Group Description	Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.
Measure Participants	29
Median (95% Confidence Interval) [Days]	14.0

10. Secondary Outcome

Title	Duration of an Alternative Response
Description	The duration of an alternative response was defined as the time from when an alternative response was achieved until the platelet count fell below 50x10^9/L.
Time Frame	Day 1 to Day 22

Outcome Measure Data

Analysis Population Description

Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration. Only participants with an alternative response were included in the analysis.

Arm/Group Title	NewGam
Arm/Group Description	Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.
Measure Participants	24
Median (95% Confidence Interval) [Days]	18.5

11. Secondary Outcome

Title	Duration of a Complete Response
Description	The duration of a complete response was defined as the time from when a complete response was achieved until the platelet count fell below 50x10^9/L.
Time Frame	Day 1 to Day 22

Outcome Measure Data

Analysis Population Description

Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration. Only participants with a complete response were included in the analysis.

Arm/Group Title	NewGam
Arm/Group Description	Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.
Measure Participants	18
Median (95% Confidence Interval) [Days]	12.5

12. Secondary Outcome

Title	Platelet Count by Visit
Description	The platelet count at each study visit are presented.
Time Frame	Day 1 to Day 22

Outcome Measure Data

Analysis Population Description

Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration.

Arm/Group Title	NewGam
Arm/Group Description	Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.
Measure Participants	36
Baseline	8.8 (5.76)
Day 2	41.6 (31.41)
Day 3	115.0 (85.58)
Day 4	154.6 (118.04)
Day 5	168.2 (149.89)
Day 6	179.3 (178.64)
Day 7	206.3 (195.75)
Day 8	186.5 (205.44)
Day 15	88.1 (130.07)
Day 22/End of treatment	41.4 (65.48)

13. Secondary Outcome

Title	Maximum Platelet Count
Description	The maximum platelet count achieved during the study is presented.
Time Frame	Day 1 to Day 22

Outcome Measure Data

Analysis Population Description

Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration.

Arm/Group Title	NewGam
Arm/Group Description	Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.
Measure Participants	36
Mean (Standard Deviation) [10^9 platelets/L]	236.9 (205.18)

14. Secondary Outcome

Title	Percentage of Responders Who Achieved a Normal Platelet Count
Description	The percentage of responders who achieved a normal platelet count is presented.
Time Frame	Day 1 to Day 22

Outcome Measure Data

Analysis Population Description

Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration. Only responders were included in the analysis.

Arm/Group Title	NewGam
Arm/Group Description	Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.
Measure Participants	29
Number (95% Confidence Interval) [Percentage of participants]	79.3 198.3%

15. Secondary Outcome

Title	Bleeding Intensity
Description	The percentage of participants with various intensities of overall bleeding, epistaxis (bleeding of the nose), oral bleeding, and skin bleeding graded as none, minor, mild, moderate, or severe at Baseline and Day 22 are reported.
Time Frame	Day 1 to Day 22

Outcome Measure Data

Analysis Population Description

Full analysis set: All participants enrolled in the study who received at least part of 1 dose of NewGam who had at least 1 post-baseline measurement of platelet concentration.

Arm/Group Title	NewGam
Arm/Group Description	Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.
Measure Participants	36
Overall - Total - Baseline	100.0 250%
Overall - Total - Day 8	100.0 250%
Overall - Total - Day 22	100.0 250%
Overall - None - Baseline	36.1 90.3%
Overall - None - Day 8	91.2 228%
Overall - None - Day 22	72.2 180.5%
Overall - Minor - Baseline	38.9 97.3%
Overall - Minor - Day 8	5.9 14.8%
Overall - Minor - Day 22	19.4 48.5%
Overall - Mild - Baseline	5.6 14%
Overall - Mild - Day 8	2.9 7.3%
Overall - Mild - Day 22	2.8 7%
Overall - Moderate - Baseline	19.4 48.5%
Overall - Moderate - Day 8	0.0 0%
Overall - Moderate - Day 22	2.8 7%
Overall - Severe - Baseline	0.0 0%
Overall - Severe - Day 8	0 0%
Overall - Severe - Day 22	2.8 7%
Epistaxis - Total - Baseline	100.0 250%
Epistaxis - Total - Day 22	100.0 250%
Epistaxis - None - Baseline	83.3 208.3%
Epistaxis - None - Day 22	91.7 229.3%
Epistaxis - Minor - Baseline	8.3 20.8%
Epistaxis - Minor - Day 22	8.3 20.8%
Epistaxis - Mild - Baseline	5.6 14%
Epistaxis - Mild - Day 22	0.0 0%
Epistaxis - Moderate - Baseline	2.8 7%
Epistaxis - Moderate - Day 22	0.0 0%
Epistaxis - Severe - Baseline	0.0 0%
Epistaxis - Severe - Day 22	0.0 0%
Oral bleeding - Total - Baseline	100.0 250%
Oral bleeding - Total - Day 22	100.0 250%
Oral bleeding - None - Baseline	75.0 187.5%
Oral bleeding - None - Day 22	86.1 215.3%
Oral bleeding - Minor - Baseline	13.9 34.8%
Oral bleeding - Minor - Day 22	8.3 20.8%
Oral bleeding - Mild - Baseline	0.0 0%
Oral bleeding - Mild - Day 22	2.8 7%
Oral bleeding - Moderate - Baseline	5.6 14%
Oral bleeding - Moderate - Day 22	2.8 7%
Oral bleeding - Severe - Baseline	5.6 14%
Oral bleeding - Severe - Day 22	0.0 0%
Skin bleeding - Total - Baseline	100.0 250%
Skin bleeding - Total - Day 22	100.0 250%
Skin bleeding - None - Baseline	41.7 104.3%
Skin bleeding - None - Day 22	77.8 194.5%
Skin bleeding - Minor - Baseline	25.0 62.5%
Skin bleeding - Minor - Day 22	22.2 55.5%
Skin bleeding - Mild - Baseline	27.8 69.5%
Skin bleeding - Mild - Day 22	0.0 0%
Skin bleeding - Moderate - Baseline	5.6 14%
Skin bleeding - Moderate - Day 22	0.0 0%
Skin bleeding - Severe - Baseline	0.0 0%
Skin bleeding - Severe - Day 22	0.0 0%

16. Secondary Outcome

Title	Percentage of Participants Who Achieved a Platelet Count > 30x10^9/L
Description	The percentage of participants who achieved a platelet count > 30x10^9/L within 1 and 2 days after infusion is reported.
Time Frame	Day 1 to Day 2

Outcome Measure Data

Analysis Population Description

Safety set: All participants enrolled in the study who received at least part of 1 dose of NewGam.

Arm/Group Title	NewGam
Arm/Group Description	Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.
Measure Participants	40
Day 1	55.0 137.5%
Day 2	77.5 193.8%

Adverse Events

Adverse Event Reporting Description	Safety set: All participants enrolled in the study who received at least part of 1 dose of NewGam.
Arm/Group Title	NewGam
Arm/Group Description	Each participant received 1 g/kg NewGam intravenously on 2 consecutive days.
All Cause Mortality
	NewGam
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	NewGam
	Affected / at Risk (%)	# Events
Total	6/40 (15%)
Blood and lymphatic system disorders
Autoimmune thrombocytopenia	3/40 (7.5%)
Gastrointestinal disorders
Dysphagia	1/40 (2.5%)
Infections and infestations
Pneumonia	1/40 (2.5%)
Sepsis	1/40 (2.5%)
Nervous system disorders
Cerebral haematoma	1/40 (2.5%)
Meningitis aseptic	1/40 (2.5%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/40 (2.5%)
Respiratory failure	1/40 (2.5%)
Other (Not Including Serious) Adverse Events
	NewGam
	Affected / at Risk (%)	# Events
Total	30/40 (75%)
Blood and lymphatic system disorders
Autoimmune thrombocytopenia	6/40 (15%)
Anaemia	5/40 (12.5%)
Idiopathic thrombocytopenic purpura	2/40 (5%)
Gastrointestinal disorders
Nausea	6/40 (15%)
Vomiting	4/40 (10%)
General disorders
Asthenia	2/40 (5%)
Chills	2/40 (5%)
Pyrexia	9/40 (22.5%)
Nervous system disorders
Headache	17/40 (42.5%)
Dizziness	3/40 (7.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.