NCT00546871

Comparison of Intravenous and Subcutaneous Administration of IGIV, 10% in Primary Immunodeficiency (PID) Subjects

Completed Phase 2, PHASE3 Results posted Last updated 19 May 2021

What this trial tests

Phase 2, PHASE3 trial testing Immune Globulin Intravenous (Human), 10% in Primary Immunodeficiency Diseases (PID) in 49 participants. Completed in 1 September 2009.

Timeline

3 October 2007

Primary endpoint
1 July 2009

1 September 2009

Quick facts

Lead sponsor	Baxalta now part of Shire
Phase	Phase 2, PHASE3
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	49
Start date	3 October 2007
Primary completion	1 July 2009
Estimated completion	1 September 2009
Sites	9 locations across United States

Drugs / interventions tested

• Immune Globulin Intravenous (Human), 10%

Conditions studied

• Primary Immunodeficiency Diseases (PID) — all drugs for Primary Immunodeficiency Diseases (PID) →

Sponsor

Baxalta now part of Shire — full company profile →

Who can join

24 Months and older, any sex, with Primary Immunodeficiency Diseases (PID). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Ratio of Area Under the Concentration Curve (AUC 0-τ)/Week Following IV Administration to SC Administration of IGIV, 10% at an Adjusted/Individual Adapted Dose (Part 3b), Expressed as a Percentage Primary · Week 12 (IV) and week 32 or 33 (SC)

Expressed as (AUC\_SC/AUC\_IV) \* 100

Group	Value	95% CI
Participants ≥12 Years Old With PK Data Part 1 and Part 3b	95.2	92.3 – 98.2

Bioavailability (Trough Levels) of IgG After Administration of IGIV, 10%, in Participants Aged 2 to <12 Years. Primary · Baseline; at each 3 or 4-week study visit in Study Part 1; at Visits 1, 5, and 9 in Study Part 2; at Visits 1, and 5 in Study Part 3a; at Visits 1, 5, and 9 in Study Part 3b; and at the end-of-study evaluation

Administration of IGIV, 10%: - Part 1 = IV administration (IV) - Parts 2, 3a, 3b = SC administration (SC)

Part 1 (IV), Screening visit (n=14)

Group	Value	95% CI
Participants Aged 2 to <12 Years	11.400	9.640 – 16.800

Part 1 (IV), 3 week Interval, Visit 1 (n=5)

Group	Value	95% CI
Participants Aged 2 to <12 Years	10.100	NA – NA

Part 1 (IV), 3 week Interval, Visit 2 (n=4)

Group	Value	95% CI
Participants Aged 2 to <12 Years	11.500	NA – NA

Part 1 (IV), 3 week Interval, Visit 3 (n=5)

Group	Value	95% CI
Participants Aged 2 to <12 Years	10.600	NA – NA

Part 1 (IV), 3 week Interval, Visit 4 (n=5)

Group	Value	95% CI
Participants Aged 2 to <12 Years	10.100	NA – NA

Part 1 (IV), 3 week Interval, Visit 5 (n=5)

Group	Value	95% CI
Participants Aged 2 to <12 Years	10.800	NA – NA

Part 1 (IV), 4 week Interval, Visit 1 (n=7)

Group	Value	95% CI
Participants Aged 2 to <12 Years	9.640	7.240 – 17.400

Part 1 (IV), 4 week Interval, Visit 2 (n=9)

Group	Value	95% CI
Participants Aged 2 to <12 Years	10.000	7.230 – 12.400

Study Part 1 (IV): Maximum Plasma Concentration (C-max) Secondary · Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.

Maximal immune globulin concentration after infusion

Group	Value	95% CI
12 Years and Older	22.7	21.0 – 25.0

Study Part 1 (IV): Minimum Plasma Concentration (C-min) Secondary · Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.

Minimal immune globulin concentration after infusion

Group	Value	95% CI
12 Years and Older	10.1	9.4 – 12.4

Study Part 1 (IV): Weight-adjusted Clearance Secondary · Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.

Computed as weight-adjusted dose divided by total AUC

Group	Value	95% CI
12 Years and Older	1.36	1.23 – 1.42

Study Part 1 (IV): Terminal Half-life Secondary · Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #3 starts) up to 28 days (+/-2 days) post-infusion.

Computed from the regression slope in the terminal phase of the model (the slope is biphasic). Terminal half life is the time it takes for the plasma concentration or the amount of immunoglobulin in the body to be reduced by 50%during the terminal phase.

Group	Value	95% CI
12 Years and Older	33.1	28.7 – 41.4

Study Part 2 (Subcutaneous (SC)): Maximum Plasma Concentration (C-max) Secondary · Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.

Maximal immune globulin concentration after infusion

Group	Value	95% CI
12 Years and Older	14.5	12.3 – 16.4

Study Part 2 (SC): Time to Maximum Immune Globulin Concentration (T-max) Secondary · Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.

Time to reach C-max

Group	Value	95% CI
12 Years and Older	4.8	3.0 – 4.9

Study Part 2 (SC): Minimum Plasma Concentration (C-min) Secondary · Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.

Minimal immune globulin concentration after infusion

Group	Value	95% CI
12 Years and Older	12.5	11.3 – 14.2

Study Part 2 (SC): Weight-adjusted Clearance Secondary · Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.

Computed as weight-adjusted dose divided by total AUC

Group	Value	95% CI
12 Years and Older	1.86	1.61 – 2.04

Study Part 3B: Maximum Plasma Concentration (C-max) Secondary · Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.

Maximal immune globulin concentration after infusion

Group	Value	95% CI
12 Years and Older	14.1	12.5 – 16.3

Study Part 3B: Time to Maximum Immune Globulin Concentration (T-max) Secondary · Pharmacokinetic evaluations: 60 minutes pre-infusion (before infusion #8 starts) up to 7 days (+/-1 day) post-infusion.

Time to reach C-max

Group	Value	95% CI
12 Years and Older	2.9	1.2 – 3.2

Adverse events — posted to ClinicalTrials.gov

Time frame: Throughout the entire study period (1 year, 9 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

IV Treatment Period

Serious: 2/49 (4%)

Deaths: —

SC Treatment Period

Serious: 2/48 (4%)

Deaths: —

Serious adverse events (4 terms)

Reaction	System	IV Treatment Period	SC Treatment Period
Sinusitis	Infections and infestations	—	—
Convulsion/seizure	Nervous system disorders	—	—
Biliary Tract Infection Bacterial	Infections and infestations	—	—
Chest pain	General disorders	—	—

Other adverse events (35 terms — click to expand)

Reaction	System	IV Treatment Period	SC Treatment Period
HEADACHE	Nervous system disorders	—	—
PYREXIA	General disorders	—	—
INFUSION SITE PAIN	General disorders	—	—
NAUSEA	Gastrointestinal disorders	—	—
VOMITING	Gastrointestinal disorders	—	—
CHILLS	General disorders	—	—
FATIGUE	General disorders	—	—
ASTHMA	Respiratory, thoracic and mediastinal disorders	—	—
OROPHARYNGEAL PAIN	Respiratory, thoracic and mediastinal disorders	—	—
ABDOMINAL PAIN UPPER	Gastrointestinal disorders	—	—
DIARRHOEA	Gastrointestinal disorders	—	—
INFUSION SITE HAEMATOMA	General disorders	—	—
EAR PAIN	Ear and labyrinth disorders	—	—
INFUSION SITE RASH	General disorders	—	—
HEART RATE INCREASED	Investigations	—	—
MUSCULOSKELETAL PAIN	Musculoskeletal and connective tissue disorders	—	—
MYALGIA	Musculoskeletal and connective tissue disorders	—	—
MIGRAINE	Nervous system disorders	—	—
LYMPHADENOPATHY	Blood and lymphatic system disorders	—	—
ABDOMINAL DISCOMFORT	Gastrointestinal disorders	—	—
ABDOMINAL PAIN	Gastrointestinal disorders	—	—
APHTHOUS STOMATITIS	Gastrointestinal disorders	—	—
CONSTIPATION	Gastrointestinal disorders	—	—
INFUSION SITE ERYTHEMA	General disorders	—	—
INFUSION SITE OEDEMA	General disorders	—	—
CONTUSION	Injury, poisoning and procedural complications	—	—
BLOOD PRESSURE SYSTOLIC INCREASED	Investigations	—	—
ARTHRALGIA	Musculoskeletal and connective tissue disorders	—	—
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	—	—
SINUS HEADACHE	Nervous system disorders	—	—
INSOMNIA	Psychiatric disorders	—	—
EPISTAXIS	Respiratory, thoracic and mediastinal disorders	—	—
NASAL CONGESTION	Respiratory, thoracic and mediastinal disorders	—	—
ECZEMA	Skin and subcutaneous tissue disorders	—	—
URTICARIA	Skin and subcutaneous tissue disorders	—	—

Most-reported serious reactions: Sinusitis, Convulsion/seizure, Biliary Tract Infection Bacterial, Chest pain.

Data from ClinicalTrials.gov NCT00546871 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the tolerability of IGIV, 10% given subcutaneously and the pharmacokinetics of immunoglobulin G (IgG) following subcutaneous (SC) treatment with IGIV, 10% in subjects with primary immunodeficiency (PID) disorders.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Infection rates and tolerability of three different immunoglobulin administration modalities in patients with primary immunodeficiency diseases.
   Wasserman RL, Gupta S, Stein M, Rabbat CJ, et al · · 2022 · cited 4× · PMID 34931880 · DOI 10.2217/imt-2021-0256
2. Effects of Body Mass and Age on the Pharmacokinetics of Subcutaneous or Hyaluronidase-facilitated Subcutaneous Immunoglobulin G in Primary Immunodeficiency Diseases.
   Li Z, Follman K, Freshwater E, Engler F, et al · · 2023 · cited 3× · PMID 37773562 · DOI 10.1007/s10875-023-01572-x
3. 2019 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference.
   · 2019 · cited 1× · PMID 30809743 · DOI 10.1007/s10875-019-00597-5