Trial Outcomes & Findings for Pharmacokinetics (PK) and Safety of Subgam-VF in Primary Immunodeficiency Diseases (NCT NCT01884311)
NCT ID: NCT01884311
Last Updated: 2018-09-12
Results Overview
Log transformed sAUC0-t, (AUC0-t standardized to one week) were analysed using a multiple linear regression model fitted including treatment, allowing for variability between treatment groups. The mean difference (Subgam-VF or Gammaplex IGIV 5%) between treatments with 90% Confidence Interval (CI) were back transformed to give an estimate of the ratio (Subgam-VF/ Gammaplex 5% IGIV) of sAUC(0-t). Data was collected at the following timepoints after week 21 of the clinical trial over a period of 1 week: Pre-dose on Day 0 and post-dose at days 1, 2, 3, 5 and 7.
COMPLETED
PHASE3
38 participants
1 week
2018-09-12
Participant Flow
Participant milestones
| Measure |
Subgam-VF
Subgam-VF is a 16% IgG and will be administered weekly, by subcutaneous infusion over a period of 26 weeks.
|
|---|---|
|
Overall Study
STARTED
|
38
|
|
Overall Study
COMPLETED
|
33
|
|
Overall Study
NOT COMPLETED
|
5
|
Reasons for withdrawal
| Measure |
Subgam-VF
Subgam-VF is a 16% IgG and will be administered weekly, by subcutaneous infusion over a period of 26 weeks.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
3
|
|
Overall Study
withdrew consent due to AEs
|
1
|
|
Overall Study
Precautionary measure
|
1
|
Baseline Characteristics
Pharmacokinetics (PK) and Safety of Subgam-VF in Primary Immunodeficiency Diseases
Baseline characteristics by cohort
| Measure |
Subgam-VF
n=38 Participants
Subgam-VF is a 16% IgG and will be administered weekly, by subcutaneous infusion over a period of 26 weeks.
|
|---|---|
|
Age, Customized
>=16 years
|
25 Participants
n=99 Participants
|
|
Age, Customized
< 16 years
|
13 Participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
36 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
35 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
38 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 1 weekPopulation: Subgam PK Population was defined as all subjects in the ITT population who had a pre-dose sample at steady state and at least 4 post-dose samples at steady state, 1 of which should have been the Day 7 PK sample. Population included 50 Subjects from GMX01 (NCT00278954), 25 Subjects from GMX04 (NCT01289847) and 38 Subjects from SCIG03.
Log transformed sAUC0-t, (AUC0-t standardized to one week) were analysed using a multiple linear regression model fitted including treatment, allowing for variability between treatment groups. The mean difference (Subgam-VF or Gammaplex IGIV 5%) between treatments with 90% Confidence Interval (CI) were back transformed to give an estimate of the ratio (Subgam-VF/ Gammaplex 5% IGIV) of sAUC(0-t). Data was collected at the following timepoints after week 21 of the clinical trial over a period of 1 week: Pre-dose on Day 0 and post-dose at days 1, 2, 3, 5 and 7.
Outcome measures
| Measure |
Subgam-VF and Gammaplex 5%
n=113 Participants
Subgam-VF
Subgam-VF is a 16% IgG and will be administered weekly, by subcutaneous infusion. The total duration of treatment will be for 26 weeks.
The initial weekly dose of Subgam-VF administered will be calculated by taking the average weekly equivalent of the subject's IGIV dose (should be stable, as in same mg/kg +/- 5%), divided by the average dosing interval in weeks (i.e. 3 or 4), multiplied by 1.37, a dose adjustment coefficient based on other licensed subcutaneous IgG products. If the subject was already receiving a weekly SCIG IgG there will be no dose adjustment.
This population included 50 Subjects from GMX01 (NCT00278954), 25 Subjects from GMX04 (NCT01289847) and 38 Subjects from SCIG03.
|
|---|---|
|
Data (Derived From Absolute Concentration) Were Pooled With Historical Data and a Treatment Variable Defined (Subgam-VF or Gammaplex 5% IGIV). Outcome Measure Defined as Log Transformed sAUC0-t Standardized to One Week.
|
0.98 Ratio
Interval 0.91 to 1.05
|
SECONDARY outcome
Timeframe: 30 weeksPopulation: The intent-to-treat population included all subjects who received at least 1 infusion of Subgam-VF.
TEAEs defined as those events with onset date between the first infusion date and 28 days after the last infusion.
Outcome measures
| Measure |
Subgam-VF and Gammaplex 5%
n=38 Participants
Subgam-VF
Subgam-VF is a 16% IgG and will be administered weekly, by subcutaneous infusion. The total duration of treatment will be for 26 weeks.
The initial weekly dose of Subgam-VF administered will be calculated by taking the average weekly equivalent of the subject's IGIV dose (should be stable, as in same mg/kg +/- 5%), divided by the average dosing interval in weeks (i.e. 3 or 4), multiplied by 1.37, a dose adjustment coefficient based on other licensed subcutaneous IgG products. If the subject was already receiving a weekly SCIG IgG there will be no dose adjustment.
This population included 50 Subjects from GMX01 (NCT00278954), 25 Subjects from GMX04 (NCT01289847) and 38 Subjects from SCIG03.
|
|---|---|
|
Number of Participants Who Experienced AEs Based on Treatment-emergent AEs (TEAEs)
No Product Related TEAEs
|
23 Participants
|
|
Number of Participants Who Experienced AEs Based on Treatment-emergent AEs (TEAEs)
SAE
|
0 Participants
|
|
Number of Participants Who Experienced AEs Based on Treatment-emergent AEs (TEAEs)
Any TEAE
|
36 Participants
|
|
Number of Participants Who Experienced AEs Based on Treatment-emergent AEs (TEAEs)
No TEAE
|
2 Participants
|
|
Number of Participants Who Experienced AEs Based on Treatment-emergent AEs (TEAEs)
Discontinued because of TEAEs
|
1 Participants
|
|
Number of Participants Who Experienced AEs Based on Treatment-emergent AEs (TEAEs)
Product Related TEAE
|
15 Participants
|
SECONDARY outcome
Timeframe: Week 26Population: The PK Dose-Adjustment population included all those in the Subgam PK population who had previous treatment with IGIV and those in the Gammaplex 5% PK population. This population was analysed to estimate a refined dose adjustment factor.
The initial weekly dose of Subgam-VF administered was calculated by taking the average weekly equivalent of the subject's IGIV dose, divided by the average dosing interval in weeks (i.e. 3 or 4), multiplied by 1.37, a dose adjustment coefficient based on other licensed subcutaneous IgG products. If the subject was already receiving a weekly SCIG IgG there will be no dose adjustment. A refined dose adjustment was estimated as 1.37/the ratio (Subgam-VF/ Gammaplex 5% IGIV) of geometric means for sAUC0-t and presented with 90% CI.
Outcome measures
| Measure |
Subgam-VF and Gammaplex 5%
n=64 Participants
Subgam-VF
Subgam-VF is a 16% IgG and will be administered weekly, by subcutaneous infusion. The total duration of treatment will be for 26 weeks.
The initial weekly dose of Subgam-VF administered will be calculated by taking the average weekly equivalent of the subject's IGIV dose (should be stable, as in same mg/kg +/- 5%), divided by the average dosing interval in weeks (i.e. 3 or 4), multiplied by 1.37, a dose adjustment coefficient based on other licensed subcutaneous IgG products. If the subject was already receiving a weekly SCIG IgG there will be no dose adjustment.
This population included 50 Subjects from GMX01 (NCT00278954), 25 Subjects from GMX04 (NCT01289847) and 38 Subjects from SCIG03.
|
|---|---|
|
Dose Refinement in Switching From Gammaplex 5% IGIV to Subgam-VF
|
1.33 Ratio
Interval 1.23 to 1.44
|
SECONDARY outcome
Timeframe: 30 weeksPopulation: Total number of participants was 38
Infusion site reactions are defined as those events with onset date between the first infusion date and 28 days after the last infusion.
Outcome measures
| Measure |
Subgam-VF and Gammaplex 5%
n=38 Participants
Subgam-VF
Subgam-VF is a 16% IgG and will be administered weekly, by subcutaneous infusion. The total duration of treatment will be for 26 weeks.
The initial weekly dose of Subgam-VF administered will be calculated by taking the average weekly equivalent of the subject's IGIV dose (should be stable, as in same mg/kg +/- 5%), divided by the average dosing interval in weeks (i.e. 3 or 4), multiplied by 1.37, a dose adjustment coefficient based on other licensed subcutaneous IgG products. If the subject was already receiving a weekly SCIG IgG there will be no dose adjustment.
This population included 50 Subjects from GMX01 (NCT00278954), 25 Subjects from GMX04 (NCT01289847) and 38 Subjects from SCIG03.
|
|---|---|
|
Number of Infusion Site Reactions
|
447 infusion site reactions
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 30 monthsPopulation: The analysis population included 50 Subjects from GMX01 (NCT00278954), 25 Subjects from GMX04 (NCT01289847) and 38 Subjects from SCIG03 Clinical Trials. A measure type of 'number' has been used as this represents the predicted change in IgG trough levels when switching between Various IgG Dosing Regimens using a Dose Adjustment Factor of 1.37
Develop a population pharmacokinetic (PK) model for IgG in PID patients following IV (Gammaplex 5%) or SC (Subgam-VF) administration; * Conduct a formal covariate analysis to assess the impact of patient demographics, and disease-related factors on the PK of IgG following IV or SC administration and to identify those patient covariates which may be utilized in or require dose adjustment; * Use the final population PK model to simulate serum IgG concentration-time profiles in a population of PID patients in order to: * Assess switching from various IgG IV and SC dosing regimens; and * Derive the weight-adjusted dose increment required to achieve a specified difference in serum IgG trough levels when Subgam-VF is administered either weekly or biweekly
Outcome measures
| Measure |
Subgam-VF and Gammaplex 5%
n=113 Participants
Subgam-VF
Subgam-VF is a 16% IgG and will be administered weekly, by subcutaneous infusion. The total duration of treatment will be for 26 weeks.
The initial weekly dose of Subgam-VF administered will be calculated by taking the average weekly equivalent of the subject's IGIV dose (should be stable, as in same mg/kg +/- 5%), divided by the average dosing interval in weeks (i.e. 3 or 4), multiplied by 1.37, a dose adjustment coefficient based on other licensed subcutaneous IgG products. If the subject was already receiving a weekly SCIG IgG there will be no dose adjustment.
This population included 50 Subjects from GMX01 (NCT00278954), 25 Subjects from GMX04 (NCT01289847) and 38 Subjects from SCIG03.
|
|---|---|
|
Population PK Model for IgG in PID Patients for Alternative Dosing Schedules.
Increase from IGIV to Weekly Subgam
|
31 % of predicted change in IgG trough
|
|
Population PK Model for IgG in PID Patients for Alternative Dosing Schedules.
Increase from IGIV to Biweekly Subgam
|
22 % of predicted change in IgG trough
|
|
Population PK Model for IgG in PID Patients for Alternative Dosing Schedules.
Decrease from Weekly Subgam to Biweekly Subgam
|
7 % of predicted change in IgG trough
|
|
Population PK Model for IgG in PID Patients for Alternative Dosing Schedules.
Increase from Weekly Subgam to twice weekly Subgam
|
2 % of predicted change in IgG trough
|
|
Population PK Model for IgG in PID Patients for Alternative Dosing Schedules.
Increase from Weekly Subgam to 3x weekly Subgam
|
3 % of predicted change in IgG trough
|
|
Population PK Model for IgG in PID Patients for Alternative Dosing Schedules.
Increase from weekly Subgam to 5x weekly Subgam
|
3 % of predicted change in IgG trough
|
|
Population PK Model for IgG in PID Patients for Alternative Dosing Schedules.
Increase from weekly Subgam to 7x weekly Subgam
|
3 % of predicted change in IgG trough
|
Adverse Events
Subgam-VF
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Subgam-VF
n=38 participants at risk
Subgam-VF is a 16% IgG and will be administered weekly, by subcutaneous infusion for a total duration of 26 weeks.
|
|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
5.3%
2/38 • Number of events 2 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
5.3%
2/38 • Number of events 2 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Gastrointestinal disorders
Diarrhoea
|
21.1%
8/38 • Number of events 10 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Gastrointestinal disorders
Vomiting
|
5.3%
2/38 • Number of events 2 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
General disorders
Chest Pain
|
5.3%
2/38 • Number of events 2 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
General disorders
Fatigue
|
7.9%
3/38 • Number of events 4 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
General disorders
Infusion Site Bruising
|
5.3%
2/38 • Number of events 3 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
General disorders
Infusion Site Erythema
|
15.8%
6/38 • Number of events 12 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
General disorders
Infusion Site Pain
|
15.8%
6/38 • Number of events 21 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
General disorders
Infusion Site Pruritus
|
10.5%
4/38 • Number of events 5 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
General disorders
Infusion Site Swelling
|
5.3%
2/38 • Number of events 6 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
General disorders
Pain
|
7.9%
3/38 • Number of events 5 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
General disorders
Pyrexia
|
15.8%
6/38 • Number of events 11 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Infections and infestations
Acute Sinusitis
|
10.5%
4/38 • Number of events 6 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Infections and infestations
Bronchitis
|
7.9%
3/38 • Number of events 3 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Infections and infestations
Gastroenteritis
|
5.3%
2/38 • Number of events 3 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Infections and infestations
Gastroenteritis Viral
|
7.9%
3/38 • Number of events 4 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Infections and infestations
Nasopharyngitis
|
26.3%
10/38 • Number of events 15 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Infections and infestations
Pharyngitis Streptococcal
|
7.9%
3/38 • Number of events 3 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Infections and infestations
Rhinitis
|
5.3%
2/38 • Number of events 2 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Infections and infestations
Sinusitis
|
10.5%
4/38 • Number of events 7 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
7.9%
3/38 • Number of events 5 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Infections and infestations
Urinary Tract Infection
|
10.5%
4/38 • Number of events 5 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Infections and infestations
Viral Upper Respiratory Tract Infection
|
13.2%
5/38 • Number of events 6 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Injury, poisoning and procedural complications
Ligament Sprain
|
5.3%
2/38 • Number of events 2 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Injury, poisoning and procedural complications
Tooth Fracture
|
5.3%
2/38 • Number of events 2 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Investigations
Coombs Direct Test Positive
|
10.5%
4/38 • Number of events 5 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
5.3%
2/38 • Number of events 2 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
5.3%
2/38 • Number of events 2 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
7.9%
3/38 • Number of events 4 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
5.3%
2/38 • Number of events 2 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma
|
5.3%
2/38 • Number of events 2 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Nervous system disorders
Headache
|
21.1%
8/38 • Number of events 12 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Renal and urinary disorders
Haemosiderinuria
|
7.9%
3/38 • Number of events 3 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
13.2%
5/38 • Number of events 9 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
7.9%
3/38 • Number of events 4 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
10.5%
4/38 • Number of events 5 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Skin and subcutaneous tissue disorders
Dermatitis Contact
|
7.9%
3/38 • Number of events 3 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.3%
2/38 • Number of events 2 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
|
Surgical and medical procedures
Tooth Extraction
|
5.3%
2/38 • Number of events 2 • 7 months
Collected during 6 months of treatment and for 28 days after the last administration of Subgam-VF
|
Additional Information
European Medical Affairs Lead
Bio Products Laboratory Ltd
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60