Open Label, Phase III Study of NABI-IGIV 10% [Immune Globulin Intravenous(Human), 10%] In Subjects With Primary Immune Deficiency Disorders (PIDD)

• Sponsor: ADMA Biologics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00538915
• Collaborator: (none)
• Enrollment: 63
• Locations: 17
• Arm: 1
• Duration (Months): 22
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if NABI-IGIV (10%) [Immune Globulin Intravenous (Human), 10%] is safe and effective in preventing serious bacterial infections (SBIs) in the treatment of patients with primary immune deficiency disorders (PIDD) when compared to historical control data.

Condition or Disease	Intervention/Treatment	Phase
Primary Immune Deficiency Disorders (PIDD)	Biological: Nabi-IGIV 10% [Immune Globulin Intravenous (Human). 10%]	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open Label, Phase III Safety, Efficacy, and Pharmacokinetic Study of NABI-IGIV 10% [Immune Globulin Intravenous (Human), 10%] in Subjects With Primary Immune Deficiency Disorders (PIDD)
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Jul 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Nabi-IGIV Infused Every 3- or 4-Weeks

Biological: Nabi-IGIV 10% [Immune Globulin Intravenous (Human). 10%]; Nabi-IGIV 10% [Immune Globulin Intravenous (Human), 10%] is a clear or slightly opalescent, colorless to pale yellow sterile solution of 10% protein concentration of immunoglobulin G (100mg/mL). It is packaged as 5g in 50mL solution and 10g in 100mL solution. Dosing will be 300-800 mg/kg based on subject's prior dosing history. Infusions will be every 3 or 4 weeks.

Outcome Measures

Primary Outcome Measures

1. Rate of Serious Bacterial Infections (SBIs) Per Person-year on Treatment [One year]

   Serious bacterial infections (SBIs) rate per person-years, including bacteremia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia and visceral abscess.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female, age ≥ 6 and ≤ 75, with a documented and confirmed pre-existing diagnosis of chronic primary immune deficiency (PIDD) with a low total immunoglobulin G (IgG) level and deficient antibody production before chronic therapy (i.e., X-linked agammaglobulinemia, common variable immunodeficiency (CVID), Hyper IgM Syndrome with immunoglobulin G (IgG) deficiency, etc).

• Currently on immune globulin intravenous (IGIV) replacement therapy at a fixed interval and dosage with a total monthly dose of immune globulin intravenous (IGIV) between 300 and 800 mg/kg that has been stable for at least 3 months prior to screening.

• Documented (within 3 months) plasma immunoglobulin G (IgG) trough level of >500 mg/dL on current immunoglobulin G (IgG) therapy [immunoglobulin G (IgG) levels may be obtained at screening if previous results not available].

• Medical records documenting infections and treatment within the previous 2 years need to be available for review.

• Subject or legal guardian(s) must have given written informed consent/assent.

• If a menstruating female, have a negative serum or urine pregnancy test within 7 days prior to the first dose of Nabi-IGIV [immune globulin intravenous (Human) 10%] and agree to use an acceptable method of contraception or be at least one year post-menopausal or surgically sterile.

Exclusion Criteria:

• Received any blood product [other than immune globulin intravenous (IGIV)] within the last 3 months prior to screening or received any investigational agent [other than immune globulin intravenous (IGIV)] within the last four weeks prior to receiving Nabi-IGIV [immune globulin intravenous (Human) 10%].

• Known history of medically significant adverse reactions to other immunoglobulin G (IgG) or blood products.

• Known selective immunoglobulin A (IgA) deficiency, history of allergic reaction to products containing immunoglobulin A (IgA) or has a history of antibodies to immunoglobulin A (IgA).

• Known significant proteinuria and/or has a history of acute renal failure/or severe renal impairment [blood urea nitrogen (BUN) or creatinine more than 1.5 times the upper limit of normal].

• Known history or current diagnosis of deep venous thrombosis.

• Known medical condition that is known to cause secondary immune deficiency, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, human immunodeficiency virus (HIV) infection, acquired immunodeficiency syndrome (AIDS), or chronic or recurrent neutropenia (absolute neutrophil count less than 500 mm3).

• Current daily use of corticosteroids (> 10 mg of prednisone equivalent /day for > 30 days), immunosuppressants or immunomodulators. (Intermittent corticosteroid use during the study is allowable, if medically necessary.)

• Known non-controllable arterial hypertension (systolic blood pressure (BP) > 160 mmHg and /or diastolic BP >100 mmHg.)

• Known anemia at screening (hemoglobin <10 g/dL).

• Subject is pregnant or lactating.

• Known history of illicit drug use within 3 months prior to the administration of the investigational product and for the study duration.

• Have any condition judged by the study physician to preclude participation in the study, including any psychological disorder, which might hinder compliance.

• Known active viral or bacterial infection or symptoms/signs consistent with such an infection within the two weeks prior to the initial dose of investigational product infusion. Subjects may be on antibiotics as long as signs/symptoms of infection have been absent for two weeks prior to the initial infusion of investigational product (IP).

• Expectation of non-compliance with the protocol procedures and visit schedule.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35294
2	Precision Trials LLC	Phoenix	Arizona	United States	85032
3	Children's Hospital of Los Angeles	Los Angeles	California	United States	90027
4	1st Allergy and Clinical Resaerch center	Centennial	Colorado	United States	80112
5	Allergy Associates of the Palm Beaches	North Palm Beach	Florida	United States	33408
6	Marietta Pulmonary Medicine	Marietta	Georgia	United States	30060
7	Rush University Medical center	Chicago	Illinois	United States	60612
8	South Bend Clinic LLP	South Bend	Indiana	United States	46617
9	Kentuky Lung Clinic, PSC	Hazard	Kentucky	United States	41701
10	Institute For Allergy & Asthma	Wheaton	Maryland	United States	20902
11	Cardinal Glennon Children's MC	Saint Louis	Missouri	United States	63104
12	Women's and Children's Hospital of Buffalo	Buffalo	New York	United States	14222
13	University Hospital Case medical center	Cleveland	Ohio	United States	44103
14	Allergy/Immunology Research Center of north Texas	Dallas	Texas	United States	75230
15	AARA Research	Dallas	Texas	United States	75231
16	Allergy, Asthma & Immunology Clinic, PA	Irving	Texas	United States	75063
17	Bellingham Asthma, Allergy Clinic	Bellingham	Washington	United States	98225

Sponsors and Collaborators

• ADMA Biologics, Inc.

Investigators

• Study Director: Shailesh Chavan, M.D., Biotest Pharmaceuticals Corporation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ADMA Biologics, Inc.
• ClinicalTrials.gov Identifier: NCT00538915
• Other Study ID Numbers: Nabi-7101
• First Posted: Oct 3, 2007
• Last Update Posted: Jul 30, 2021
• Last Verified: Feb 1, 2012

• Keywords provided by ADMA Biologics, Inc.: immunodeficiency; humoral immunity; antibody deficiency; PID; PIDD
• Additional relevant MeSH terms: Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes; Immunoglobulins; Antibodies; gamma-Globulins; Immunoglobulins, Intravenous; Rho(D) Immune Globulin

Study Results

Participant Flow

Recruitment Details	First subject enrolled: 24 September 2007. Last subject completed: 24 July 2009. 15 investigative sites, hospital clinics and private physician clinics.
Pre-assignment Detail	This was an open study. All enrolled subjects received study medication.

Arm/Group Title	Nabi-IGIV 10% Administered On A 3-Week or 4-Week Interval
Arm/Group Description	Each subject received a total Nabi-IGIV 10% [Immune Globulin Intravenous (Human), 10%] infusion of 300-800 mg/kg per month administered intravenously every 3 or 4 weeks for approximately 1 year.
Period Title: Overall Study
STARTED	63
COMPLETED	52
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	Nabi-IGIV 10% Administered On A 3-Week or 4-Week Interval
Arm/Group Description	Each subject received a total Nabi-IGIV 10% [Immune Globulin Intravenous (Human), 10%] infusion of 300-800 mg/kg per month administered intravenously every 3 or 4 weeks for approximately 1 year.
Overall Participants	63
Age (Count of Participants)
<=18 years	12 19%
Between 18 and 65 years	42 66.7%
>=65 years	9 14.3%
Sex: Female, Male (Count of Participants)
Female	32 50.8%
Male	31 49.2%

Outcome Measures

1. Primary Outcome

Title	Rate of Serious Bacterial Infections (SBIs) Per Person-year on Treatment
Description	Serious bacterial infections (SBIs) rate per person-years, including bacteremia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia and visceral abscess.
Time Frame	One year

Outcome Measure Data

Analysis Population Description

63 subjects enrolled, received treatment and included in the Safety population. 5 subjects excluded from the Intent To Treat (ITT) population due to significant, excessive protocol violations and an insufficient number of infusions to elicit the intended effect.

Arm/Group Title	Nabi-IGIV 10% Administered On A 3-Week or 4-Week Interval
Arm/Group Description	Each subject received a total Nabi-IGIV 10% [Immune Globulin Intravenous (Human), 10%] infusion of 300-800 mg/kg administered intravenously every 3 or 4 weeks for approximately 1 year.
Measure Participants	58
Number [SBIs Per Total Person-Years]	0.035

Adverse Events

Time Frame	An event was only included in the analysis of Adverse Events (AEs) if it had an onset date between the first administration of study drug and 28 days after the last administration of study drug, inclusive.
Arm/Group Title	Nabi-IGIV 10% Administered On A 3-Week or 4-Week Interval
Arm/Group Description	Each subject received a total Nabi-IGIV 10% [Immune Globulin Intravenous (Human), 10%] infusion of 300-800 mg/kg per month administered intravenously every 3 or 4 weeks for approximately 1 year.
All Cause Mortality
	Nabi-IGIV 10% Administered On A 3-Week or 4-Week Interval
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Nabi-IGIV 10% Administered On A 3-Week or 4-Week Interval
	Affected / at Risk (%)	# Events
Total	7/63 (11.1%)
Gastrointestinal disorders
Colitis	1/63 (1.6%)	1
Intestinal Obstruction	1/63 (1.6%)	1
Vomiting	1/63 (1.6%)	1
Infections and infestations
Appendicitis	1/63 (1.6%)	1
Obstructive Chronic Bronchitis With Acute Exacerbation	1/63 (1.6%)	1
Pneumonia Bacterial	1/63 (1.6%)	1
Injury, poisoning and procedural complications
Hip Fracture	1/63 (1.6%)	1
Metabolism and nutrition disorders
Dehydration	1/63 (1.6%)	1
Psychiatric disorders
Mental Status Changes	1/63 (1.6%)	1
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	1/63 (1.6%)	1
Vascular disorders
Hypotension	1/63 (1.6%)	1
Other (Not Including Serious) Adverse Events
	Nabi-IGIV 10% Administered On A 3-Week or 4-Week Interval
	Affected / at Risk (%)	# Events
Total	47/63 (74.6%)
Gastrointestinal disorders
Diarrhea	4/63 (6.3%)	4
Nausea	5/63 (7.9%)	10
General disorders
Fatigue	15/63 (23.8%)	62
Infusion Site Reaction	5/63 (7.9%)	6
Infections and infestations
Sinusitis	5/63 (7.9%)	5
Investigations
Blood Pressure Increased	4/63 (6.3%)	5
Nervous system disorders
Dizziness	4/63 (6.3%)	4
Headache	27/63 (42.9%)	147
Lethargy	4/63 (6.3%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.