Study of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy

A Multicentre Study of the Efficacy, Tolerability, Safety, and Pharmacokinetics of Immune Globulin Subcutaneous (Human) IgPro20 in Subjects With Primary Immunodeficiency

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00542997

Enrollment

Registered

2007-10-12

Start date

2007-09-30

Completion date

2009-08-31

Last updated

2011-09-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Autosomal Recessive Agammaglobulinemia, Common Variable Immunodeficiency, X-linked Agammaglobulinemia

Keywords

Subcutaneous immune globulin, SCIG

Brief summary

The objective of this study is to assess the efficacy, tolerability, safety and pharmacokinetics of IgPro20 in patients with primary humoral immunodeficiency (PID).

Detailed description

This study consisted of a 12-week wash-in/wash-out period followed by a 28-week efficacy period. During the 28-week efficacy period, subjects visited the study site at least every 4 weeks for efficacy and safety evaluations and additionally recorded details regarding IgPro20 dose and certain aspects of efficacy and safety in a diary. Pharmacokinetic (PK) parameters were assessed in a sub-group of subjects during 1 treatment interval at steady-state (Week 28 ± 1).

Interventions

BIOLOGICALHuman Normal Immunoglobulin for Subcutaneous Administration (IGSC)

IgPro20 is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals. The initial weekly dose was determined based on subjects' previous treatment. Dose adjustments could be performed during the wash-in/wash-out period at the discretion of the investigator.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

2 Years to 65 Years

Healthy volunteers

Inclusion criteria

* Subjects with primary humoral immunodeficiency, namely with a diagnosis of Common Variable Immunodeficiency (CVID) as defined by the Pan-American Group for Immunodeficiency (PAGID) and European Society for Immunodeficiencies (ESID), X-linked agammaglobulinemia (XLA) as defined by PAGID and ESID, or Autosomal Recessive Agammaglobulinemia * Chest X-ray or CT scan obtained within 1 year prior to enrolment

Exclusion criteria

* Newly diagnosed PID, i.e. subjects who have not previously received immunoglobulin replacement therapy * Ongoing serious bacterial infection at the time of screening * Malignancies of lymphoid cells such as lymphocytic leukemia, Non-Hodgkin's lymphoma and immunodeficiency with thymoma * Allergic or other severe reactions to immunoglobulins or other blood products associated with high anti-IgA Additional criteria may apply and examination by an investigator is required to determine eligibility.

Design outcomes

Primary

Measure	Time frame	Description
Total Serum IgG Trough Levels	Up to 6 months prior to first IgPro20 treatment (Pre-study treatment) and Week 12 to 17 (IgPro20 treatment)	Total IgG trough levels for IgPro20 treatment at steady state were compared with documented trough level data for IgG treatment received prior to enrolling in the study (either subcutaneous or intravenous IgG). For this purpose, 6 consecutive IgPro20 trough values (obtained prior to infusions 12 to 17) per subject were aggregated to the subject's median value and then median values across subjects were summarised using descriptive statistics. The same procedure was applied to pre-study treatment using the 3 most recent IgG trough values ≥ 5 g/L obtained prior to the first IgPro20 infusion.

Secondary

Measure	Time frame	Description
Annual Rate of Clinically Documented Serious Bacterial Infections (PPE Population)	Efficacy period: week 12 to week 40 after study start or to the completion visit	Serious bacterial infections (SBIs) included bacterial pneumonia, bacteraemia/septicaemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. Diagnosis of the SBIs was based on the presence of predefined clinical signs and symptoms as well as on laboratory parameters. The annual rate was calculated based on the total number of SBIs and the total number of study days during the efficacy period for all subjects in the PPE population and adjusted to 365 days.
Annual Rate of Infection Episodes	Efficacy period: week 12 to week 40 after study start or to the completion visit	The annual rate of episodes was calculated based on the total number of any infection type and the total number of study days during the efficacy period for all subjects in the ITT population and adjusted to 365 days.
Annual Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Activities Due to Infections	Efficacy period: week 12 to week 40 after study start or to the completion visit	The annual rate was calculated based on the total number of days out of work/school/kindergarten/day care or unable to perform normal activities due to infections in the efficacy period divided by the total number of days in the efficacy period for all subjects and adjusted to 365 days.
Annual Rate of the Number of Days of Hospitalization Due to Infections	Efficacy period: week 12 to week 40 after study start or to the completion visit	The annual rate was calculated based on the total number of days of hospitalization due to infections in the efficacy period divided by the total number of days in the efficacy period for all subjects and adjusted to 365 days.
Annual Rate of Antibiotic Use for Infection Prophylaxis and Treatment	Efficacy period: week 12 to week 40 after study start or to the completion visit	The annual rate was calculated based on the total number of days of antibiotic use in the efficacy period divided by the total number of days in the efficacy period for all subjects and adjusted to 365 days.
Annual Rate of Clinically Documented Serious Bacterial Infections (ITT Population)	Efficacy period: week 12 to week 40 after study start or to the completion visit	Serious bacterial infections (SBIs) included bacterial pneumonia, bacteraemia/septicaemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. Diagnosis of the SBIs was based on the presence of predefined clinical signs and symptoms as well as on laboratory parameters. The annual rate was calculated based on the total number of SBIs and the total number of study days during the efficacy period for all subjects in the ITT population and adjusted to 365 days.

Other

Measure	Time frame	Description
Area Under the Concentration-Time Curve (AUC_last) of Total Serum IgG	Week 28 (±1week)	AUC\_last = Area under the concentration-time curve until last measured concentration.
Area Under the Concentration-Time Curve (AUCτ) of Total Serum IgG	Week 28 (±1week)	AUCτ = Area under the concentration-time curve during regular dosing interval;
Timepoint of Maximum Concentration (Tmax) of Total Serum IgG	Week 28 (±1week)	—
Maximum Concentration (Cmax) of Total Serum IgG	Week 28 (±1week)	—

Countries

France, Germany, Italy, Poland, Romania, Spain, Sweden, Switzerland, United Kingdom

Participant flow

Recruitment details

This multinational study enrolled subjects at 15 of the participating study centers in Europe.

Pre-assignment details

Screening took place 1 to 4 weeks prior to the first IgPro20 infusion.

Participants by arm

Arm	Count
IgPro20 (All Treated) All subjects enrolled and treated with subcutaneous infusion of IgPro20	51
Total	51

Withdrawals & dropouts

Period	Reason	FG000
Efficacy Period	Adverse Event	3
Wash in / Wash Out Period	Adverse Event	3
Wash in / Wash Out Period	Withdrawal by Subject	2

Baseline characteristics

Characteristic	IgPro20 (All Treated)
Age Continuous	22.6 years STANDARD_DEVIATION 16.02
Age, Customized 12 to < 16 years	5 Participants
Age, Customized 16 to < 65 years	28 Participants
Age, Customized 2 to < 12 years	18 Participants
Race/Ethnicity, Customized White	51 Participants
Sex: Female, Male Female	16 Participants
Sex: Female, Male Male	35 Participants
Type of Primary Immunodeficiency Autosomal recessive agammaglobulinemia (ARAG)	1 Participants
Type of Primary Immunodeficiency Common variable immunodeficiency (CVID)	30 Participants
Type of Primary Immunodeficiency X-linked agammaglobulinemia (XLA)	20 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	50 / 51
serious Total, serious adverse events	5 / 51

Outcome results

Primary

Total Serum IgG Trough Levels

Total IgG trough levels for IgPro20 treatment at steady state were compared with documented trough level data for IgG treatment received prior to enrolling in the study (either subcutaneous or intravenous IgG). For this purpose, 6 consecutive IgPro20 trough values (obtained prior to infusions 12 to 17) per subject were aggregated to the subject's median value and then median values across subjects were summarised using descriptive statistics. The same procedure was applied to pre-study treatment using the 3 most recent IgG trough values ≥ 5 g/L obtained prior to the first IgPro20 infusion.

Time frame: Up to 6 months prior to first IgPro20 treatment (Pre-study treatment) and Week 12 to 17 (IgPro20 treatment)

Population: Intention-to-treat (ITT) population analysis. The ITT population included all subjects who were treated with IgPro20 during the efficacy period (starting with Week 12). For 2 subjects in the ITT population, the pre-study treatment IgG trough levels were not available.

Arm	Measure	Value (MEAN)	Dispersion
IgPro20	Total Serum IgG Trough Levels	8.10 g/L	Standard Deviation 1.44
Pre-study IgG Treatment	Total Serum IgG Trough Levels	7.49 g/L	Standard Deviation 1.57

Secondary

Annual Rate of Antibiotic Use for Infection Prophylaxis and Treatment

The annual rate was calculated based on the total number of days of antibiotic use in the efficacy period divided by the total number of days in the efficacy period for all subjects and adjusted to 365 days.