Study to compare the blood levels and safety of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases

• Register: EUCTR
• Last refreshed on: 30 May 2016
• Main ID: EUCTR2013-002290-21-HU
• Date of registration: 14/07/2014
• Prospective Registration: Yes
• Primary sponsor: Bio Products Laboratory Limited
• Public title: Study to compare the blood levels and safety of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases
• Scientific title: A Phase III, Multicenter, Open-label, Randomized, Two-Period, Crossover Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases - Study to compare Gammaplex 10% & 5% in Primary Immunodeficiency
• Date of first enrolment: 13/10/2014
• Target sample size: 48
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002290-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Hungary, United Kingdom, United States

Contacts

• Name: Medical Director
• Affiliation: Bio Products Laboratory Limited

• Name: Medical Director
• Affiliation: Bio Products Laboratory Limited

Key inclusion & exclusion criteria

Inclusion criteria:
1. Adult cohort: The subject is aged 16 to 55 years inclusive, is of either sex, and belongs to any ethnic group.
Pediatric cohort: The subject is aged 2 to 15 years inclusive, is of either sex, weighs at least 10 kg, and belongs to any ethnic group.
2. The subject has primary immunodeficiency disease, e.g. common variable immunodeficiency, X-linked and autosomal forms of agammaglobulinemia, hyper-IgM syndrome. Isolated deficiency of a single IgG subclass or of specific antibodies without hypogammaglobulinemia per se, does not qualify for inclusion.
3. The subject is currently receiving a licensed IGIV (or investigational stage III, IIIb IGIV) at a dose that has not changed by ± 50% of the mean dose for at least three months before study entry and is between 300 and 800 mg/kg/infusion. The infusion interval must be either every 21 or every 28 days.
4. The subject must have a trough level = 6 g/L (600 mg/dL). At least one documented trough level must be available from the three months before Screening.
5. The subject must have documentation from the last three consecutive routine IGIV infusions for the following, before the first infusion in this study: dose of IGIV, treatment intervals, and trade name (or identity) of the IGIV treatment.
6. Female subjects of childbearing potential must have a negative result on an HCG-based pregnancy test at Screening.
7. Females who are or become sexually active must practice contraception using a method of proven reliability for the study duration.
8. The subject is willing to comply with all aspects of the protocol for the duration of the study.
9. The subject has signed an informed consent form and assent form (if applicable).
Are the trial subjects under 18? yes
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
1. The subject has a history of any severe anaphylactic reaction to blood or any blood-derived product.
2. The subject has selective IgA deficiency, history of reaction to products containing IgA, or has a history of antibodies to IgA.
3. The subject has cellular or innate impaired immunity (i.e. only subjects with humoral impaired immunity may be included).
4. The subject has evidence of an active infection at the time of enrolment.
5. The subject has previously completed or withdrawn from this study.
6. The subject is currently receiving, or has received, any investigational agent other than an IGIV within the prior three months.
7. The subject is pregnant or is nursing.
8. The subject has positive results for any of the following at Screening: Serological test for HIV 1 and 2, HCV, or HBsAg
NAT for HCV
NAT for HIV
9. The subject has levels > 2.5 times the upper limit of normal, as defined at the central laboratory, of any of the following at Screening: Alanine aminotransaminase Aspartate aminotransaminase
10. The subject has severe renal impairment (defined as serum creatinine greater than two times the upper limit of normal or blood urea nitrogen 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.
11. The subject is known to abuse alcohol, opiates, psychotropic agents, or other chemicals or drugs, or has done so within the past 12 months.
12. The subject has a history of deep vein thrombosis or thrombotic complications of IGIV therapy.
13. 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 the Investigator feels may interfere with the conduct of the study.
14. The subject has an acquired immunodeficiency condition such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, or chronic or recurrent neutropenia (absolute neutrophil count < 1 × 10 9 /L).
15. The subject is receiving the following medication:
Steroids (long-term daily, = 0.15 mg of prednisone equivalent/kg/day). Requirement for short or intermittent courses of steroids would not exclude a subject.
Immunosuppressive drugs
Immunomodulatory drugs
Planned vaccination with live attenuated virus vaccines during the trial or during three months after last dosage administration
16. The subject has uncontrolled arterial hypertension (systolic blood pressure > 160 mm Hg and/or diastolic blood pressure > 100 mm Hg).
17. The subject has anemia (hemoglobin < 10 g/dL) at Screening.
18. The subject is known to be intolerant to any component of Gammaplex, such as sorbitol (i.e. intolerance to fructose) or glycine.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Primary immunodeficiency diseases
MedDRA version: 17.0 Level: PT Classification code 10064859 Term: Primary immunodeficiency syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Trade Name: Gammaplex
Product Name: Gammaplex
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Human Normal Immunoglobulin
Concentration unit: g/l gram(s)/litre
Concentration type: range
Concentration number: 45-55

Product Name: Gammaplex 10
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Human Normal Immunoglobulin
Concentration unit: g/l gram(s)/litre
Concentration type: range
Concentration number: 90-110

Primary Outcome(s)

Primary end point(s): Bioequivalence of AUC0-28, the concentration of IgG in the blood during the period 0 to 28 days after infusion with Gammaplex 10 and 5%

Main Objective: To demonstrate the bioequivalence (similarity) of Gammaplex® 10 intravenous immunoglobulin (IGIV) and Gammaplex® 5% IGIV using a pharmacokinetic measure (area under the curve within a 28-day dosing interval (AUC0-28)) in adults.

Secondary Objective: The secondary objectives are:
To demonstrate the bioequivalence of Gammaplex® 10 IGIV and Gammaplex® 5% IGIV using area under the curve within a 21-day dosing interval (AUC0-21) in adults;
To assess the blood levels (PK) of Gammaplex 10 IGIV and Gammaplex 5% IGIV (including IgG trough levels) and safety and tolerability in adults;
To assess the PK of Gammaplex 10 IGIV (including IgG trough levels) and safety and tolerability in children.

Timepoint(s) of evaluation of this end point: Pharmacokinetic samples to measure AUC0-28 will be collected from adult patients after the final infusion of each treatment (Gammaplex 10 and 5%). This will be completed in the 28 days after visits 5 (20-24 weeks) and 10 (40-44 weeks)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: - PK samples to measure AUC0-21 will be collected from adult patients after the final infusion of each treatment (Gammaplex 10 and 5%). This will be completed in the 21 days after visits 5 (15-18 weeks) and 10 (30-33 weeks)
- PK and safety and tolerability will be assessed in adults up to 44 weeks
- PK and safety and tolerability will be assessed in pediatric patients up to 24 weeks

Secondary end point(s): - Bioequivalence of AUC0-21 in adult patients after infusion with Gammaplex 10 and 5%
- PK of Gammaplex 10 IGIV and Gammaplex 5% IGIV (including IgG trough levels) and safety and tolerability in adult subjects;
- PK of Gammaplex 10 IGIV (including IgG trough levels) and safety and tolerability in pediatric subjects.

Secondary ID(s)

2013-002290-21-GB

GMX07

NCT01963143

Source(s) of Monetary Support

Bio Products Laboratory Limited