A Study to Find Out How Safe and Effective Gammaplex® is in Young People With Primary Immunodeficiency

• Sponsor: Bio Products Laboratory (Other)
• Overall Status: Completed
• CT.gov ID: NCT01289847
• Collaborator: (none)
• Enrollment: 25
• Locations: 10
• Arm: 1
• Duration (Months): 37
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The main objective is to determine the efficacy of Gammaplex by measuring the number of serious acute bacterial infections during treatment with Gammaplex over a 12 month period. The secondary objectives are to assess the safety and tolerability of Gammaplex and to compare the data collected from adult subjects with PID from the GMX01 study

Condition or Disease	Intervention/Treatment	Phase
Primary Immune Deficiency Disorders; Common Variable Immunodeficiency; X-linked Agammaglobulinemia; Hyper-IgM Syndrome; Wiskott-Aldrich Syndrome	Biological: Gammaplex	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase IV, Multicenter, Open-Label Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Gammaplex in Primary Immunodeficiency Diseases (PID) in Children and Adolescents
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gammaplex	Biological: Gammaplex; GAMMAPLEX 5g/100 mL, dose is 300-800 mg/kg/infusion every 21 or 28 days, intravenously. The total duration of treatment with GAMMAPLEX will be 12 months with a 3 month follow-up.

Outcome Measures

Primary Outcome Measures

1. Adverse Events [12 months]

   Number of subjects with serious, acute, bacterial infections as a measure of efficacy

Secondary Outcome Measures

1. Therapeutic Efficacy [From week 15 onwards]

   Number and proportion of subjects who maintain trough IgG levels at least as high as the average of the 2 previous trough levels before the first Gammaplex infusion

2. Therapeutic Efficacy [12 months]

   Number of days off school

3. Therapeutic Efficacy [12 months]

   Number of days in hospital

4. Therapeutic Efficacy [12 months]

   Visits to physicians and/or emergency room

5. Therapeutic Efficacy [12 months]

   Number of days on therapeutic antibiotics

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 the ages of or is equal to 2 and 16 years of age, 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, which has as a significant component of hypogammaglobulinemia and/or antibody deficiency (e.g. common variable immunodeficiency, X-linked and autosomal forms of agammaglobulinemia, hyper-IgM syndrome, Wiskott-Aldrich Syndrome). NB Isolated deficiency of a single IgG subclass, or of specific antibodies without hypogammaglobulinemia per se, does not qualify for inclusion.

• Subjects already receiving IGIV replacement therapy require the following before their first infusion of Gammaplex:

• Documented IGIV dose(s) and treatment intervals for the last 2 consecutive routine IGIV treatments (one of which can be the screening visit result). The previous doses should also meet the following conditions before study entry: Have not changed by ± 50% of the mean dose for at least 3 months; be between 300 and 800 mg/kg/infusion; be given every 21-28 days, inclusive; be a licensed or investigational product (Phase III or IIIb).

• Documented previous IgG trough levels for the last 2 consecutive routine IGIV treatments for the last 2 consecutive routine IGIV treatments: Maintained at least 300 mg/dL above baseline serum IgG levels (defined as before initiation of any gamma globulin treatment for that subject); must be more than/equal to 600 mg/dL.

• If a subject is a female of child-bearing potential, she must have a negative result on an HCG-based pregnancy test.

• If a subject is a female who is or becomes sexually active, she must practice contraception by using a method of proven reliability for the duration of the study.

• The subject is willing to comply with all aspects of the protocol, including blood sampling, for the duration of the study.

• The subject, if old enough (generally 6 years to 16), has signed a Child Assent Form and the subject's parent or legal guardian has signed the Informed Consent Form, both approved by the IEC/IRB.

Exclusion Criteria:

• Has not been treated with IGIV (treatment naive subject)

• 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 Gammaplex, such as sorbitol (i.e. intolerance to fructose).

• The subject has selective IgA deficiency, history of reaction to products containing IgA, or has a history of antibodies to IgA.

• Subjects who have completed the study and subjects who have withdrawn cannot participate in the study for a second time.

• The subject is currently receiving, or has received, any investigational agent, other than an immune serum globulin (ISG) preparation that is being evaluated in a Phase III or IIIb study, 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 or other forms of commercially available and licensed ISG. If an unlicensed ISG product that is in Phase III or IIIb has been given, the subject cannot be infused with Gammaplex until 20 days after the last dose was given.

• The 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 of any of the following: (Alanine transaminase (ALT); Aspartate transaminase (AST) Lactate dehydrogenase (LDH)).

• The subject has a severe renal impairment (defined as serum creatinine greater than 2 times the upper limit of normal or BUN greater than 2.5 times the upper limit of normal for the range of the laboratory doing the analysis); the subject is on dialysis; the subject has a history of acute renal failure.

• The subject is known to abuse alcohol, opiates, psychotropic agents, or other chemicals or drugs, or has done so within the past 12 months.

• 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, 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, chronic or recurrent neutropenia (ANC < 1000 x 109/L) or AIDS known to cause secondary immune deficiency, or is post or recovering from hematopoietic stem cell transplantation.

• The subject is receiving the following medication: Systemic long-term corticosteroids (i.e. not intermittent or burst, daily, >1 mg of prednisone equivalent/kg/day).

• The subject is receiving Immunosuppressive or Immunomodulatory drugs.

• The subject has non-controlled arterial hypertension.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Medicine, University of California	Irvine	California	United States	92697.
2	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
3	IMMUNOe International Reseach Centers	Centennial	Colorado	United States	80112
4	Family Allergy & Asthma Center, PC	Atlanta,	Georgia	United States	30342
5	Rush University Medical Center	Chicago,	Illinois	United States	60612
6	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
7	Allergy, Asthma & Immunology Clinic, P.A	Irving	Texas	United States	75063
8	Children's Hospital of Richmond, VA	Richmond	Virginia	United States	23219
9	Hospital de Niňos Roberto del Río	Santiago		Chile	8380418
10	Safra Children's Hospital, Sheba Medical Center	Tel-Hashomer		Israel	52621

Sponsors and Collaborators

• Bio Products Laboratory

Investigators

• Study Director: Tim J. Aldwinckle, MD, Medical Director

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bio Products Laboratory
• ClinicalTrials.gov Identifier: NCT01289847
• Other Study ID Numbers: GMX04; IND 12569
• First Posted: Feb 4, 2011
• Last Update Posted: Dec 23, 2014
• Last Verified: Dec 1, 2014

• Keywords provided by Bio Products Laboratory: Primary Immune Deficiency Disorders; Common Variable Immunodeficiency; X-linked agammaglobulinemia; Hyper-IgM syndrome; Wiskott-Aldrich Syndrome; Immunoglobulins; Bacterial Infections
• Additional relevant MeSH terms: Wiskott-Aldrich Syndrome; Agammaglobulinemia; Hyper-IgM Immunodeficiency Syndrome; Hyper-IgM Immunodeficiency Syndrome, Type 1; Primary Immunodeficiency Diseases; Immunologic Deficiency Syndromes; Common Variable Immunodeficiency; Syndrome; gamma-Globulins; Immunoglobulins, Intravenous; Rho(D) Immune Globulin

Study Results

Participant Flow

Recruitment Details	First enrollment: 06 April 2011; Last Subject completed 23 April 2014; Nine recruiting sites globally: United States (US) (seven sites), Chile (one site) and Israel (one site)
Pre-assignment Detail	This was a Phase IV, multicentre, open-label, non-randomised study. All enrolled subjects received study medication.

Arm/Group Title	Gammaplex
Arm/Group Description	Gammaplex: GAMMAPLEX 5g/100 mL, dose is 300-800 mg/kg/infusion every 21 or 28 days, intravenously. The total duration of treatment with GAMMAPLEX will be 12 months with a 3 month follow-up.
Period Title: Overall Study
STARTED	25
COMPLETED	24
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Gammaplex
Arm/Group Description	Gammaplex: GAMMAPLEX 5g/100 mL, dose is 300-800 mg/kg/infusion every 21 or 28 days, intravenously. The total duration of treatment with GAMMAPLEX will be 12 months with a 3 month follow-up.
Overall Participants	25
Age, Customized (participants) [Number]
2 to 5 year age group	3 12%
6 to 11 year age group	12 48%
12 to 16 year age group	10 40%
Sex: Female, Male (Count of Participants)
Female	6 24%
Male	19 76%
Region of Enrollment (participants) [Number]
United States	22 88%
Israel	2 8%
Chile	1 4%

Outcome Measures

1. Primary Outcome

Title	Adverse Events
Description	Number of subjects with serious, acute, bacterial infections as a measure of efficacy
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT)

Arm/Group Title	Gammaplex
Arm/Group Description	Gammaplex: GAMMAPLEX 5g/100 mL, dose is 300-800 mg/kg/infusion every 21 or 28 days, intravenously. The total duration of treatment with GAMMAPLEX will be 12 months with a 3 month follow-up.
Measure Participants	25
Number [participants]	2 8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gammaplex
	Comments	For the primary efficacy analysis, the SABI rate for GAMMAPLEX and the upper bound of its one-sided 99% confidence interval (CI) were estimated by using the exact method for a one-sample Poisson rate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	one-sample Poisson rate
	Comments

2. Secondary Outcome

Title	Therapeutic Efficacy
Description	Number and proportion of subjects who maintain trough IgG levels at least as high as the average of the 2 previous trough levels before the first Gammaplex infusion
Time Frame	From week 15 onwards

Outcome Measure Data

Analysis Population Description

Seven subjects (28.0%) maintained trough IgG levels at all visits that were at least as high as the average of the two previous levels before the first infusion

Arm/Group Title	Gammaplex
Arm/Group Description	Gammaplex: GAMMAPLEX 5g/100 mL, dose is 300-800 mg/kg/infusion every 21 or 28 days, intravenously. The total duration of treatment with GAMMAPLEX will be 12 months with a 3 month follow-up.
Measure Participants	25
Number [participants]	7 28%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gammaplex
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	one-sample Poisson method
	Comments

3. Secondary Outcome

Title	Therapeutic Efficacy
Description	Number of days off school
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gammaplex
Arm/Group Description	Gammaplex: GAMMAPLEX 5g/100 mL, dose is 300-800 mg/kg/infusion every 21 or 28 days, intravenously. The total duration of treatment with GAMMAPLEX will be 12 months with a 3 month follow-up.
Measure Participants	25
Mean (Standard Deviation) [days]	7.8 (12.06)

4. Secondary Outcome

Title	Therapeutic Efficacy
Description	Number of days in hospital
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gammaplex
Arm/Group Description	Gammaplex: GAMMAPLEX 5g/100 mL, dose is 300-800 mg/kg/infusion every 21 or 28 days, intravenously. The total duration of treatment with GAMMAPLEX will be 12 months with a 3 month follow-up.
Measure Participants	25
Mean (Standard Deviation) [days]	0.3 (0.87)

5. Secondary Outcome

Title	Therapeutic Efficacy
Description	Visits to physicians and/or emergency room
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gammaplex
Arm/Group Description	Gammaplex: GAMMAPLEX 5g/100 mL, dose is 300-800 mg/kg/infusion every 21 or 28 days, intravenously. The total duration of treatment with GAMMAPLEX will be 12 months with a 3 month follow-up.
Measure Participants	25
Mean (Standard Deviation) [visits]	4.0 (4.67)

6. Secondary Outcome

Title	Therapeutic Efficacy
Description	Number of days on therapeutic antibiotics
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gammaplex
Arm/Group Description	Gammaplex: GAMMAPLEX 5g/100 mL, dose is 300-800 mg/kg/infusion every 21 or 28 days, intravenously. The total duration of treatment with GAMMAPLEX will be 12 months with a 3 month follow-up.
Measure Participants	25
Mean (Standard Deviation) [days]	32.0 (28.28)

Adverse Events

Time Frame	AEs were documented from the date Informed Consent Form or Assent was signed until 30 days after the last dose of Gammaplex was infused.
Arm/Group Title	Gammaplex
Arm/Group Description	Gammaplex: GAMMAPLEX 5g/100 mL, dose is 300-800 mg/kg/infusion every 21 or 28 days, intravenously. The total duration of treatment with GAMMAPLEX will be 12 months with a 3 month follow-up.
All Cause Mortality
	Gammaplex
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gammaplex
	Affected / at Risk (%)	# Events
Total	3/25 (12%)
Gastrointestinal disorders
Acute Gastroenterirtis (AGE)	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
left lower lobe pneumonia	1/25 (4%)	1
left lower lobe pneumonia	1/25 (4%)	1
Other (Not Including Serious) Adverse Events
	Gammaplex
	Affected / at Risk (%)	# Events
Total	25/25 (100%)
Blood and lymphatic system disorders
Lymphadenopathy	2/25 (8%)	3
Cardiac disorders
Tachycardia	3/25 (12%)	6
Gastrointestinal disorders
Nausea	6/25 (24%)	8
Vomiting	5/25 (20%)	8
Diarrhoea	3/25 (12%)	4
Abdominal pain upper	2/25 (8%)	2
General disorders
Pyrexia	9/25 (36%)	15
Fatigue	5/25 (20%)	11
Malaise	5/25 (20%)	7
Chest discomfort	3/25 (12%)	6
Infusion site erythema	2/25 (8%)	2
Pain	2/25 (8%)	2
Infections and infestations
Nasopharyngitis	8/25 (32%)	11
Acute sinusitis	7/25 (28%)	9
Upper respiratory tract infection	6/25 (24%)	8
Viral upper respiratory tract infection	5/25 (20%)	7
Pharyngitis streptococcal	4/25 (16%)	4
Sinusitis	3/25 (12%)	7
Gastroenteritis viral	3/25 (12%)	4
Pharyngitis	3/25 (12%)	4
Bronchitis	2/25 (8%)	3
Lobar pneumonia	2/25 (8%)	3
Bronchitis acute	2/25 (8%)	2
Influenza	2/25 (8%)	2
Otitis media	2/25 (8%)	2
Otitis media acute	2/25 (8%)	2
Pneumonia	2/25 (8%)	2
Rhinitis	2/25 (8%)	2
Injury, poisoning and procedural complications
Joint sprain	2/25 (8%)	2
Skin laceration	2/25 (8%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	4/25 (16%)	4
Myalgia	2/25 (8%)	13
Nervous system disorders
Headache	13/25 (52%)	39
Respiratory, thoracic and mediastinal disorders
Cough	8/25 (32%)	19
Nasal congestion	8/25 (32%)	17
Rhinorrhoea	4/25 (16%)	4
Dyspnoea	3/25 (12%)	3
Pharyngolaryngeal pain	3/25 (12%)	3
Epistaxis	2/25 (8%)	3
Nasal oedema	2/25 (8%)	3
Wheezing	2/25 (8%)	3
Skin and subcutaneous tissue disorders
Eczema	2/25 (8%)	3
Vascular disorders
Hypotension	4/25 (16%)	12
Diastolic hypertension	3/25 (12%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is an agreement between the PI and Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results. Publication of Study results will be allowed only with prior written approval from Sponsor. At the request of Sponsor, the Institution and/or Investigator shall delete any Confidential Information pertaining to Sponsor's Inventions from any proposed publications prior to submitting or presenting the materials.