Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01963143
• Date of registration: 13/09/2013
• Prospective Registration: Yes
• Primary sponsor: Bio Products Laboratory
• Public title: Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases GMX07
• 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
• Date of first enrolment: February 2014
• Target sample size: 48
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01963143
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Hungary, United Kingdom, United States

Contacts

• Name: Eric Wolford
• Affiliation: Bio Products Laboratory

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
(Immunoglobulin M) 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 (human
chorionic gonadotropin) 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).

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 (Immunoglobulin A), 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 (Nucleic acid amplification technique)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 amino transaminase

- Aspartate amino transaminase

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 × 109/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

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. hereditary intolerance to fructose) or glycine.

- Chronic conditions would be as per the Investigator's opinion however for this
study the guidance is that the condition has been present for at least 6 months.



Age minimum: 2 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Common Variable Immunodeficiency

Hyper-IgM Syndrome

Primary Immune Deficiency Disorders

X-linked Agammaglobulinaemia

Intervention(s)

Biological: Gammaplex (5%)

Biological: Gammaplex 10

Primary Outcome(s)

Primary Bioequivalence Analysis - Area Under the Curve Within a 28-day Dosing Interval (AUC0-28) in Adult Subjects [Time Frame: After a minimum 5 infusions on each product, at pre-infusion, 10 minutes before end of infusion, 1, 3, 6, 24, 48 hours, 4, 7, 14, 21 and 28 days post-infusion]

Secondary Outcome(s)

Secondary Bioequivalence Analysis - Area Under the Curve Within a 21-Day Dosing Interval (AUC0-21) in Adult Subjects [Time Frame: After a minimum 5 infusions on each product, at pre-infusion, 10 minutes before end of infusion, 1, 3, 6, 24, 48 hours, 4, 7, 14 and 21 days post-infusion]

Secondary Bioequivalence Analysis - IgG Trough Levels [Time Frame: After a minimum 5 infusions on each product, at pre-infusion.]

Secondary ID(s)

GMX07

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 29/03/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01963143