Safety and Efficacy Study of Flebogamma 5% DIF IGIV in Pediatric Subjects

• Sponsor: Instituto Grifols, S.A. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00634569
• Collaborator: (none)
• Enrollment: 24
• Locations: 7
• Arm: 1
• Duration (Months): 36
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a multi-center, open-label study to assess the efficacy and safety of Flebogamma 5% DIF in the pediatric population.

Condition or Disease	Intervention/Treatment	Phase
Primary Immune Deficiency Disease	Biological: Flebogamma 5% DIF	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of the Efficacy and Safety of Flebogamma 5% DIF [Immune Globulin Intravenous (Human)] for Replacement Therapy in Pediatric Subjects With Primary Immunodeficiency Diseases.
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Flebogamma 5% DIF	Biological: Flebogamma 5% DIF; Intravenous Immune Globulin (Human)

Outcome Measures

Primary Outcome Measures

1. Serious Bacterial Infections. [12 months]

   Total number of Bacterial pneumonia, bacteremia or sepsis, osteomyelitis/septic arthritis, visceral abscess or bacterial meningitis

Secondary Outcome Measures

1. Days of School/Usual Activities Missed Per Year [12 months]

   Mean Days of school/usual activities missed per subject/year

2. Days of Hospitalization Per Year [12 months]

   Mean Days of hospitalization per subject/year

3. Number of Visits to Physician/ER Room for Acute Problems [12 months]

   Mean Number of visits to physician/ER room for acute problems

4. Other Infections Documented by Fever and Physical Exam or Positive Radiograph. [12 months]

5. Number of Infectious Episodes Per Year [12 months]

   Mean Number of infectious episodes per subject/year

6. Number of Days on Antibiotics (Prophylactic and Therapeutic). [12 months]

   Median Combined number of days on prophylactic and therapeutic antibiotics

7. Number of Adverse Events [12 months]

   Total Number of Adverse Events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 16 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The subject is between 2 and 16 years old, of either sex, belonging to any ethnic group, and above a minimum weight of 10 kg (this weight is based on the amount of blood required for testing).

• The subject has a primary immunodeficiency disease, (e.g., common variable immunodeficiency, X-linked and autosomal forms of agammaglobulinemia, hyper-IgM syndrome, Wiskott-Aldrich Syndrome).

• The subject has been receiving licensed IGIV replacement therapy at a dose that has not changed by + 50% of the mean dose on a mg/kg basis for at least 3 months before study entry and has maintained a trough level at least 300 mg/dL above baseline serum IgG levels.

• Trough levels of IgG, dose of IGIV, and treatment intervals for the last 2 consecutive routine IGIV treatments must be documented for each subject before the first infusion in this study can be administered.

• If a subject is an adolescent female (> 12 years of age) who is or becomes sexually active, she must have a negative result on a pregnancy test (HCG-based assay).

• The subject, if old enough (generally 6 years to 16) has signed an informed Child Assent form and the subject's parent or legal guardian has signed an informed consent form, both approved by the Institutional Review Board.

Exclusion Criteria:

• Adult patient (> 17 years old).

• The subject has a history of any severe anaphylactic reaction to blood or any blood-derived product.

• The subject is known to be intolerant to any component of the products, such as sorbitol (i.e., intolerance to fructose).

• The subject has selective IgA deficiency or has demonstrable antibodies to IgA.

• The subject is currently receiving, or has received, any investigational agent within the prior 3 months.

• The subject has been exposed to blood or any blood product or derivative within the last 6 months, other than a commercially available IGIV.

• The adolescent subject is pregnant or is nursing.

• The subject, at screening, has levels greater than 2.5 times the upper limit of normal as defined at the central laboratory for pediatric patients of any of the following:

• ALT

• AST

• LDH

• The subject has a severe pre-existing renal impairment (defined by serum creatinine greater than 2 times the ULN or BUN greater than 2.5 times the ULN for that laboratory, or any subject who is on dialysis) or any history of acute renal failure.

• The subject has a history of DVT or thrombotic complications of IGIV therapy.

• The subject suffers from any acute or chronic medical condition (e.g., renal disease or predisposing conditions for renal disease, coronary artery disease, or protein losing state) that, in the opinion of the Investigator, may interfere with the conduct of the study.

• The subject has an acquired medical condition such as lymphocytic leukemia, chronic or recurrent neutropenia (ANC less than 1000), or AIDS known to cause secondary immune deficiency, or is s/p hematopoetic stem cell transplantation.

• The subject is receiving the following medication:

• Systemic corticosteroids (long-term, i.e., not intermittent or burst, daily, > 1 mg of prednisone equivalent/kg/day). Topical steroids (ie- nasal, inhaled for asthma, and/or skin preparations for eczema) are not exclusionary.

• Immunosuppressive drugs

• Immunomodulatory drugs

• The subject has non-controlled arterial hypertension (systolic blood pressure > 160 mm Hg and/or diastolic blood pressure > 100 mm Hg).

• The subject has anemia (hemoglobin < 10 g/dL) at screening.

• The subject and/or parent/legal guardian of the subject is unlikely to adhere to the protocol requirements of the study or is likely to be uncooperative or unable to provide from the patient a storage serum sample at the screening visit. (Please note, a pre-treatment serum sample to be stored at -94° F (-70º C) for possible future testing is absolutely required).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of South Florida	St. Petersburg	Florida	United States	33701-4899
2	Family Allergy & Asthma Center, PC	Atlanta	Georgia	United States	30342
3	Rush University Medical Center	Chicago	Illinois	United States
4	The Allergy and Asthma Center	Fort Wayne	Indiana	United States	46804
5	The Children's Hospital of Buffalo	Buffalo	New York	United States	14222
6	Pennsylvania State University, Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
7	Children's Hospital and Regional Medial Center	Seattle	Washington	United States	98195-7110

Sponsors and Collaborators

• Instituto Grifols, S.A.

Investigators

• Principal Investigator: Mark Ballow, MD, Children's Hospital of Buffalo

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Instituto Grifols, S.A.
• ClinicalTrials.gov Identifier: NCT00634569
• Other Study ID Numbers: IG-0705
• First Posted: Mar 13, 2008
• Last Update Posted: Feb 2, 2017
• Last Verified: Dec 1, 2016

• Keywords provided by Instituto Grifols, S.A.: CVID, XLA, hyper IgM syndrome, Wiskott-Aldrich Syndrome
• Additional relevant MeSH terms: Primary Immunodeficiency Diseases; Deficiency Diseases; Immunologic Deficiency Syndromes; gamma-Globulins; Immunoglobulins, Intravenous; Rho(D) Immune Globulin

Study Results

Participant Flow

Arm/Group Title	21-day Dosing	28-day Dosing
Arm/Group Description	IGIV given every 21-days (225-600 mg/kg)	IGIV given every 28-days (300-800 mg/kg)
Period Title: Overall Study
STARTED	14	10
COMPLETED	14	5
NOT COMPLETED	0	5

Baseline Characteristics

Arm/Group Title	21-day Dosing	28-day Dosing	Total
Arm/Group Description	IGIV given every 21-days (225-600 mg/kg)	IGIV given every 28-days (300-800 mg/kg)	Total of all reporting groups
Overall Participants	14	10	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.6 (4.3)	9.7 (4.9)	9.0 (4.53)
Gender (Count of Participants)
Female	4 28.6%	1 10%	5 20.8%
Male	10 71.4%	9 90%	19 79.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	14 100%	10 100%	24 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	2 20%	2 8.3%
White	14 100%	8 80%	22 91.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Serious Bacterial Infections.
Description	Total number of Bacterial pneumonia, bacteremia or sepsis, osteomyelitis/septic arthritis, visceral abscess or bacterial meningitis
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	21-day Dosing	28-day Dosing
Arm/Group Description	IGIV given every 21-days (225-600 mg/kg)	IGIV given every 28-days (300-800 mg/kg)
Measure Participants	14	10
Number [Total serious bacterial infections]	1	0

2. Secondary Outcome

Title	Days of School/Usual Activities Missed Per Year
Description	Mean Days of school/usual activities missed per subject/year
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Subjects
Arm/Group Description	Intent-to-treat population
Measure Participants	24
Mean (Standard Deviation) [Days]	2.0 (3.33)

3. Secondary Outcome

Title	Days of Hospitalization Per Year
Description	Mean Days of hospitalization per subject/year
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Subjects
Arm/Group Description	Intent-to-treat population
Measure Participants	24
Mean (Standard Deviation) [Days]	0.2 (1.04)

4. Secondary Outcome

Title	Number of Visits to Physician/ER Room for Acute Problems
Description	Mean Number of visits to physician/ER room for acute problems
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Subjects
Arm/Group Description	Intent-to-treat population
Measure Participants	24
Mean (Standard Deviation) [Visits]	0 (0.0)

5. Secondary Outcome

Title	Other Infections Documented by Fever and Physical Exam or Positive Radiograph.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Subjects
Arm/Group Description	Intent-to-treat population
Measure Participants	24
Mean (Standard Deviation) [Number of other infections]	0 (0.0)

6. Secondary Outcome

Title	Number of Infectious Episodes Per Year
Description	Mean Number of infectious episodes per subject/year
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Subjects
Arm/Group Description	Intent-to-treat population
Measure Participants	24
Mean (Standard Deviation) [Infectious episodes]	0.9 (1.44)

7. Secondary Outcome

Title	Number of Days on Antibiotics (Prophylactic and Therapeutic).
Description	Median Combined number of days on prophylactic and therapeutic antibiotics
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Subjects
Arm/Group Description	Intent-to-treat population
Measure Participants	24
Median (Standard Deviation) [Days]	72 (150.45)

8. Secondary Outcome

Title	Number of Adverse Events
Description	Total Number of Adverse Events
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Subjects
Arm/Group Description	Intent-to-treat population
Measure Participants	24
Number [All Adverse Events]	159

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	Systematic temporal assessment of AEs (by vital sign measurement up to 72 hours post-infusion) occurring over 1 year
Arm/Group Title	All Subjects
Arm/Group Description	Intent-to-treat population
All Cause Mortality
	All Subjects
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Subjects
	Affected / at Risk (%)	# Events
Total	1/24 (4.2%)
Ear and labyrinth disorders
Deafness	1/24 (4.2%)	1
Musculoskeletal and connective tissue disorders
Cellulitis	1/24 (4.2%)	1
Femoral neck fracture	1/24 (4.2%)	1
Respiratory, thoracic and mediastinal disorders
Bronchiectasis	1/24 (4.2%)	1
Other (Not Including Serious) Adverse Events
	All Subjects
	Affected / at Risk (%)	# Events
Total	15/24 (62.5%)
Cardiac disorders
Tachycardia	6/24 (25%)	16
General disorders
Headache	10/24 (41.7%)	31
Infections and infestations
Pyrexia	7/24 (29.2%)	19
Nervous system disorders
Diastolic hypotension	5/24 (20.8%)	20
Hypotension	6/24 (25%)	19

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.