Trial Outcomes & Findings for Extension Study of Subcutaneous Immunoglobulin Human in Patients With Primary Immunodeficiency (PID) (NCT NCT00719680)

NCT ID: NCT00719680

Last Updated: 2014-04-02

Results Overview

The annualized rate was based on the total number of infections and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days. Acute serious bacterial infections included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

21 participants

Primary outcome timeframe

For the duration of the study, up to approximately 104 weeks

Results posted on

2014-04-02

Participant Flow

Participant milestones

Participant milestones
Measure	IgPro20 A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Overall Study STARTED	21
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	IgPro20 A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Overall Study Adverse Event	1
Overall Study Lost to Follow-up	1
Overall Study Withdrawal by Subject	3

Baseline Characteristics

Extension Study of Subcutaneous Immunoglobulin Human in Patients With Primary Immunodeficiency (PID)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IgPro20 n=21 Participants A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Age, Continuous	42.4 years STANDARD_DEVIATION 18.53 • n=5 Participants
Age, Customized >= 2 to < 12 years	1 participants n=5 Participants
Age, Customized >= 12 to < 16 years	1 participants n=5 Participants
Age, Customized >= 16 to < 65 years	16 participants n=5 Participants
Age, Customized >= 65 years	3 participants n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: For the duration of the study, up to approximately 104 weeks

Population: The Intention-to-Treat (ITT) population comprised all subjects treated with study medication during any study period.

Outcome measures

Outcome measures
Measure	IgPro20 n=11950 Subject Study Days A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Annualized Rate of Serious Bacterial Infection (Intention-to-Treat Population)	0.06 infections per subject year

PRIMARY outcome

Timeframe: For the duration of the study, up to approximately 104 weeks

Population: The Per-Protocol Efficacy population comprised all subjects who completed at least 48 weeks of the efficacy period that started with the first IgPro20 dose in this study.

Outcome measures

Outcome measures
Measure	IgPro20 n=11037 Subject Study Days A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Annualized Rate of Serious Bacterial Infection (Per-Protocol Efficacy Population)	0.03 infections per subject year

SECONDARY outcome

Timeframe: For the duration of the study, up to approximately 104 weeks

Population: The ITT population comprised all subjects treated with study medication during any study period.

The annualized rate was based on the total number of infections and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.

Outcome measures

Outcome measures
Measure	IgPro20 n=11950 Subject Study Days A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Annualized Rate of Any Infection	2.38 infections per subject year

SECONDARY outcome

Timeframe: Before infusion at Weeks 1, 24, 48, 72, and 96

Population: The ITT population comprised all subjects treated with study medication during any study period.

Mean of individual median total IgG trough concentration.

Outcome measures

Outcome measures
Measure	IgPro20 n=21 Participants A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Trough Levels of Total Immunoglobulin G (IgG) Serum Concentrations	11.98 g/L Standard Deviation 3.65

SECONDARY outcome

Timeframe: For the duration of the study, up to approximately 104 weeks

Population: The ITT population comprised all subjects treated with study medication during any study period.

Outcome measures

Outcome measures
Measure	IgPro20 n=21 Participants A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Number of Days Out of Work / School / Kindergarten / Day Care or Inability to Perform Normal Activities Due to Infection	6.67 days Standard Deviation 13.49

SECONDARY outcome

Timeframe: For the duration of the study, up to approximately 104 weeks

Population: The ITT population comprised all subjects treated with study medication during any study period.

The annualized rate was based on the total number of days out of work / school / kindergarten / day care or inability to perform normal activities due to infection, and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.

Outcome measures

Outcome measures
Measure	IgPro20 n=11950 Subject Study Days A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Inability to Perform Normal Activities Due to Infection	4.28 days per subject year

SECONDARY outcome

Timeframe: For the duration of the study, up to approximately 104 weeks

Population: The ITT population comprised all subjects treated with study medication during any study period.

Outcome measures

Outcome measures
Measure	IgPro20 n=21 Participants A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Number of Days of Hospitalization Due to Infection	0.857 days Standard Deviation 2.726

SECONDARY outcome

Timeframe: For the duration of the study, up to approximately 104 weeks

Population: The ITT population comprised all subjects treated with study medication during any study period.

The annualized rate was based on the total number of days of hospitalization due to infection and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.

Outcome measures

Outcome measures
Measure	IgPro20 n=11950 Subject Study Days A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Annualized Rate of Hospitalization Due to Infection	0.55 days per subject year

SECONDARY outcome

Timeframe: For the duration of the study, up to approximately 104 weeks

Population: The ITT population comprised all subjects treated with study medication during any study period.

Annualized rate of days with antibiotics for infection prophylaxis and treatment.

Outcome measures

Outcome measures
Measure	IgPro20 n=11950 Subject Exposure Days A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Use of Antibiotics for Infection Prophylaxis and Treatment	83.87 days per subject year Interval 5.0 to 673.0

SECONDARY outcome

Timeframe: For the duration of the study, up to approximately 104 weeks

Population: The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period.

The rate of AEs was the number of AEs over the number of infusions administered. At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities.

Outcome measures

Outcome measures
Measure	IgPro20 n=1735 Infusions A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Rate of All AEs by Relatedness and Severity All	0.661 AEs per infusion
Rate of All AEs by Relatedness and Severity Unrelated	0.137 AEs per infusion
Rate of All AEs by Relatedness and Severity At least possibly related	0.524 AEs per infusion
Rate of All AEs by Relatedness and Severity Mild	0.575 AEs per infusion
Rate of All AEs by Relatedness and Severity Moderate	0.076 AEs per infusion
Rate of All AEs by Relatedness and Severity Severe	0.010 AEs per infusion

SECONDARY outcome

Timeframe: For the duration of the study, up to approximately 104 weeks

Population: The AT safety population comprised all subjects treated with the study medication during any study period.

At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities.

Outcome measures

Outcome measures
Measure	IgPro20 n=21 Participants A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Relatedness and Severity of All AEs (Percentage of Total AEs) Unrelated	20.7 percentage of total AEs
Relatedness and Severity of All AEs (Percentage of Total AEs) At least possibly related	79.3 percentage of total AEs
Relatedness and Severity of All AEs (Percentage of Total AEs) Mild	87.0 percentage of total AEs
Relatedness and Severity of All AEs (Percentage of Total AEs) Moderate	11.5 percentage of total AEs
Relatedness and Severity of All AEs (Percentage of Total AEs) Severe	1.5 percentage of total AEs

SECONDARY outcome

Timeframe: Within 24 or 72 hours after each infusion

Population: The AT safety population comprised all subjects treated with the study medication during any study period.

AEs were considered temporally associated if they occurred between the start of infusion and within 24 or 72 hours after the end of infusion.

Outcome measures

Outcome measures
Measure	IgPro20 n=21 Participants A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Number of Subjects With Any Temporally Associated Adverse Event (AE) Within 24 or 72 Hours After an Infusion AEs within 24 hours	21 participants
Number of Subjects With Any Temporally Associated Adverse Event (AE) Within 24 or 72 Hours After an Infusion AEs within 72 hours	21 participants

SECONDARY outcome

Timeframe: Within 24 or 72 hours after each infusion

Population: The AT safety population comprised all subjects treated with the study medication during any study period.

The rate of AEs was the number of AEs over the number of infusions administered. AEs were considered temporally associated if they occurred between the start of infusion and within 24 or 72 hours after the end of infusion.

Outcome measures

Outcome measures
Measure	IgPro20 n=1735 Infusions A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Rate of Temporally Associated AEs Within 24 or 72 Hours of an Infusion AEs within 24 hours	0.322 AEs per infusion
Rate of Temporally Associated AEs Within 24 or 72 Hours of an Infusion AEs within 72 hours	0.575 AEs per infusion

SECONDARY outcome

Timeframe: For the duration of the study, up to approximately 104 weeks

Population: The AT safety population comprised all subjects treated with the study medication during any study period.

In addition to the standard MedDRA System Organ Class (SOC) AE assignments, the category of 'local reactions' was defined to provide the possibility for a combined analysis of local reactions and included AEs of infusion site oedema, infusion site reaction, injection site pain, injection site rash, and injection site reaction. Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities.

Outcome measures

Outcome measures
Measure	IgPro20 n=21 Participants A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Number of Subjects Reporting Mild, Moderate, or Severe Local AEs Total	19 participants
Number of Subjects Reporting Mild, Moderate, or Severe Local AEs Mild	16 participants
Number of Subjects Reporting Mild, Moderate, or Severe Local AEs Moderate	3 participants
Number of Subjects Reporting Mild, Moderate, or Severe Local AEs Severe	0 participants

SECONDARY outcome

Timeframe: At weeks 1, 12, 24, 36, 48, 60, 72, 84, and 96

Population: The AT safety population comprised all subjects treated with the study medication during any study period.

Vital signs included blood pressure (systolic and diastolic), heart rate, and body temperature.

Outcome measures

Outcome measures
Measure	IgPro20 n=21 Participants A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Number of Subjects With Clinically Significant Changes From Baseline to the Completion Visit in Vital Signs	0 participants

SECONDARY outcome

Timeframe: At Week 1, and study completion (approximately 104 weeks)

Population: The AT safety population comprised all subjects treated with the study medication during any study period.

Routine laboratory parameters included hematology, blood chemistry, and urinalysis parameters.

Outcome measures

Outcome measures
Measure	IgPro20 n=21 Participants A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Number of Subjects With Clinically Significant Changes From Baseline to the Completion Visit in Routine Laboratory Parameters	0 participants

SECONDARY outcome

Timeframe: At Week 1, and study completion (approximately 104 weeks)

Population: The AT safety population comprised all subjects treated with the study medication during any study period.

Viral safety markers included human immunodeficiency virus (HIV)-1, HIV-2, hepatitis A virus (HAV), HBV, HCV, and parvovirus B19.

Outcome measures

Outcome measures
Measure	IgPro20 n=21 Participants A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Number of Subjects With Clinically Significant Changes From Baseline to the Completion Visit in Viral Safety Markers	0 participants

Adverse Events

IgPro20

Serious events: 4 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	IgPro20 n=21 participants at risk A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
Infections and infestations Cellulitis	4.8% 1/21 • Number of events 1 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Infections and infestations Pneumonia	4.8% 1/21 • Number of events 1 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	4.8% 1/21 • Number of events 2 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Gastrointestinal disorders Diarrhea	4.8% 1/21 • Number of events 1 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period

Other adverse events

Other adverse events
Measure	IgPro20 n=21 participants at risk A liquid formulation of normal human IgG at a concentration of 20%. IgPro20 was administered as a subcutaneous infusion weekly or twice weekly, depending on the investigator's judgment and the subject's preference.
General disorders Injection site reaction	47.6% 10/21 • Number of events 248 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
General disorders Infusion site reaction	42.9% 9/21 • Number of events 614 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Infections and infestations Nasopharyngitis	33.3% 7/21 • Number of events 10 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	28.6% 6/21 • Number of events 12 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Musculoskeletal and connective tissue disorders Arthralgia	23.8% 5/21 • Number of events 5 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
General disorders Fatigue	23.8% 5/21 • Number of events 33 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
General disorders Influenza-like illness	19.0% 4/21 • Number of events 7 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Gastrointestinal disorders Nausea	19.0% 4/21 • Number of events 4 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Gastrointestinal disorders Abdominal pain	14.3% 3/21 • Number of events 4 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Psychiatric disorders Anxiety	14.3% 3/21 • Number of events 3 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Musculoskeletal and connective tissue disorders Back pain	14.3% 3/21 • Number of events 10 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Gastrointestinal disorders Diarrhea	9.5% 2/21 • Number of events 3 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Nervous system disorders Headache	14.3% 3/21 • Number of events 10 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Gastrointestinal disorders Abdominal pain upper	9.5% 2/21 • Number of events 6 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Respiratory, thoracic and mediastinal disorders Asthma	9.5% 2/21 • Number of events 2 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Investigations Blood creatinine increased	9.5% 2/21 • Number of events 2 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
General disorders Chest pain	9.5% 2/21 • Number of events 2 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Respiratory, thoracic and mediastinal disorders Cough	9.5% 2/21 • Number of events 3 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Psychiatric disorders Depression	9.5% 2/21 • Number of events 2 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Nervous system disorders Dizziness	9.5% 2/21 • Number of events 2 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Gastrointestinal disorders Dysphagia	9.5% 2/21 • Number of events 4 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
General disorders Injection site pain	9.5% 2/21 • Number of events 4 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Blood and lymphatic system disorders Lymphadenopathy	9.5% 2/21 • Number of events 4 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Nervous system disorders Migraine	9.5% 2/21 • Number of events 2 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Musculoskeletal and connective tissue disorders Myalgia	9.5% 2/21 • Number of events 2 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Skin and subcutaneous tissue disorders Pruritus	9.5% 2/21 • Number of events 3 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
General disorders Pyrexia	9.5% 2/21 • Number of events 2 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Infections and infestations Bronchitis	23.8% 5/21 • Number of events 7 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Infections and infestations Clostridial infection	9.5% 2/21 • Number of events 3 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Infections and infestations Pharyngitis	9.5% 2/21 • Number of events 2 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Infections and infestations Pharyngitis streptococcal	9.5% 2/21 • Number of events 3 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Infections and infestations Upper respiratory tract infection	28.6% 6/21 • Number of events 6 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Infections and infestations Viral infection	9.5% 2/21 • Number of events 4 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Infections and infestations Viral upper respiratory tract infection	9.5% 2/21 • Number of events 2 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period
Infections and infestations Sinusitis	66.7% 14/21 • Number of events 24 • From the time of informed consent until study completion, up to approximately 121 weeks The All-Treated (AT) safety population comprised all subjects treated with the study medication during any study period

Additional Information

Clinical Trial Disclosure Manager

CSL Behring

Phone: Use email contact

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee CSL agreements may vary with individual investigators; however, CSL will not prohibit any investigator from publishing. CSL supports the publication of results from all centers of a multi-center trial and requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER