Trial Outcomes & Findings for Study to Investigate Efficacy, Safety and Pharmacokinetics of BT595 in Subjects With PID (NCT NCT02810444)
NCT ID: NCT02810444
Last Updated: 2023-07-20
Results Overview
The primary efficacy endpoint was the rate of acute serious bacterial infections, ie, the mean number of acute serious bacterial infections \[SBIs as defined by EMA and FDA\] per subject-year.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
81 participants
Primary outcome timeframe
approx. 12 month treatment period
Results posted on
2023-07-20
Participant Flow
Participant milestones
| Measure |
BT595
Subjects received BT595 (100 mg/mL human normal immunoglobulin) at doses between 0.2 and 0.8 g per kg body weight (bw) (2 to 8 mL/kg bw), either at a Q3W or Q4W schedule. The initial doses and dosage interval had to be consistent with the subject's prestudy IVIg treatment.
|
|---|---|
|
Overall Study
STARTED
|
81
|
|
Overall Study
Treatment Started
|
67
|
|
Overall Study
COMPLETED
|
60
|
|
Overall Study
NOT COMPLETED
|
21
|
Reasons for withdrawal
| Measure |
BT595
Subjects received BT595 (100 mg/mL human normal immunoglobulin) at doses between 0.2 and 0.8 g per kg body weight (bw) (2 to 8 mL/kg bw), either at a Q3W or Q4W schedule. The initial doses and dosage interval had to be consistent with the subject's prestudy IVIg treatment.
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|---|---|
|
Overall Study
Screen Failures
|
14
|
|
Overall Study
Withdrawal by Subject
|
4
|
|
Overall Study
Adverse Event
|
3
|
Baseline Characteristics
Study to Investigate Efficacy, Safety and Pharmacokinetics of BT595 in Subjects With PID
Baseline characteristics by cohort
| Measure |
BT595
n=67 Participants
Subjects received BT595 (100 mg/mL human normal immunoglobulin) at doses between 0.2 and 0.8 g per kg body weight (bw) (2 to 8 mL/kg bw), either at a Q3W or Q4W schedule. The initial doses and dosage interval had to be consistent with the subject's prestudy IVIg treatment.
|
|---|---|
|
Age, Categorical
<=18 years
|
18 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
44 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
30 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
37 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
66 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
28 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
21 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
Russia
|
11 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: approx. 12 month treatment periodPopulation: The primary analysis intended to demonstrate that the SBI rate (upper limit of the 1-sided 99% CI) was \<1.0 per subject-year in the overall FAS
The primary efficacy endpoint was the rate of acute serious bacterial infections, ie, the mean number of acute serious bacterial infections \[SBIs as defined by EMA and FDA\] per subject-year.
Outcome measures
| Measure |
BT595
n=67 Participants
Subjects received BT595 (100 mg/mL human normal immunoglobulin) at doses between 0.2 and 0.8 g per kg body weight (bw) (2 to 8 mL/kg bw), either at a Q3W or Q4W schedule. The initial doses and dosage interval had to be consistent with the subject's prestudy IVIg treatment.
|
|---|---|
|
Rate of Acute Serious Bacterial Infections
|
0.015 SBI rate per subject-year
|
SECONDARY outcome
Timeframe: approx. 12 month treatment periodPopulation: Full analysis set
Total IgG levels \[g/L\] before each infusion, mean (SD)
Outcome measures
| Measure |
BT595
n=67 Participants
Subjects received BT595 (100 mg/mL human normal immunoglobulin) at doses between 0.2 and 0.8 g per kg body weight (bw) (2 to 8 mL/kg bw), either at a Q3W or Q4W schedule. The initial doses and dosage interval had to be consistent with the subject's prestudy IVIg treatment.
|
|---|---|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Baseline, Q4W
|
7.824 g/L
Standard Deviation 2.7705
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 1 (Week 0), Q4W
|
7.824 g/L
Standard Deviation 2.7705
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 2 (Week 4), Q4W
|
8.278 g/L
Standard Deviation 2.5919
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 3 (Week 8), Q4W
|
8.246 g/L
Standard Deviation 2.3970
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 4 (Week 12), Q4W
|
8.410 g/L
Standard Deviation 2.2998
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 5 (Week 16), Q4W
|
8.634 g/L
Standard Deviation 3.4997
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 6 (Week 20), Q4W
|
8.203 g/L
Standard Deviation 2.2912
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 7 (Week 24), Q4W
|
8.298 g/L
Standard Deviation 2.3822
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Baseline, Q3W
|
10.064 g/L
Standard Deviation 2.6829
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 1 (Week 0), Q3W
|
10.261 g/L
Standard Deviation 2.7216
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 2 (Week 3), Q3W
|
10.422 g/L
Standard Deviation 2.9521
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 3 (Week 6), Q3W
|
10.509 g/L
Standard Deviation 2.9857
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 4 (Week 9), Q3W
|
10.050 g/L
Standard Deviation 3.0155
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 5 (Week 12), Q3W
|
10.267 g/L
Standard Deviation 3.2398
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 12 (Week 44), Q4W
|
8.336 g/L
Standard Deviation 2.0893
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 6 (Week 15), Q3W
|
10.026 g/L
Standard Deviation 3.2135
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 7 (Week 18), Q3W
|
10.032 g/L
Standard Deviation 2.2755
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 8 (Week 21), Q3W
|
10.268 g/L
Standard Deviation 2.7719
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 9 (Week 24), Q3W
|
9.889 g/L
Standard Deviation 2.1752
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 10 (Week 27), Q3W
|
10.343 g/L
Standard Deviation 2.2324
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 11 (Week 30), Q3W
|
10.188 g/L
Standard Deviation 2.6981
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 12 (Week 33), Q3W
|
10.427 g/L
Standard Deviation 2.7320
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 13 (Week 36), Q3W
|
10.087 g/L
Standard Deviation 2.6267
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 14 (Week 39), Q3W
|
10.245 g/L
Standard Deviation 2.4434
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 15 (Week 42), Q3W
|
10.539 g/L
Standard Deviation 2.2490
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 16 (Week 45), Q3W
|
10.045 g/L
Standard Deviation 2.7147
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 17 (Week 48), Q3W
|
9.877 g/L
Standard Deviation 2.0190
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 18 (Week 51), Q3W
|
10.412 g/L
Standard Deviation 2.4921
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Follow-up, Q3W
|
10.415 g/L
Standard Deviation 2.6176
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 13 (Week 48), Q4W
|
8.479 g/L
Standard Deviation 2.3571
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 14 (Week 52), Q4W
|
8.437 g/L
Standard Deviation 2.1703
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 11 (Week 40), Q4W
|
8.181 g/L
Standard Deviation 2.1706
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 15 (extra dose administered), Q4W
|
8.950 g/L
Standard Deviation 0.6608
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Follow-up, Q4W
|
8.461 g/L
Standard Deviation 2.2248
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Screening, Q3W
|
10.238 g/L
Standard Deviation 2.4700
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Screening, Q4W
|
8.467 g/L
Standard Deviation 3.4562
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 8 (Week 28), Q4W
|
8.308 g/L
Standard Deviation 2.1087
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 9 (Week 32), Q4W
|
8.410 g/L
Standard Deviation 2.2353
|
|
IgG Trough Levels (Total IgG) Before Each Infusion
Infusion 10 (Week 36), Q4W
|
8.264 g/L
Standard Deviation 2.2994
|
SECONDARY outcome
Timeframe: approx. 12 month treatment periodPopulation: Full analysis set
The annual rate of infections was calculated as the number of all infections (serious plus nonserious) per subject-year
Outcome measures
| Measure |
BT595
n=67 Participants
Subjects received BT595 (100 mg/mL human normal immunoglobulin) at doses between 0.2 and 0.8 g per kg body weight (bw) (2 to 8 mL/kg bw), either at a Q3W or Q4W schedule. The initial doses and dosage interval had to be consistent with the subject's prestudy IVIg treatment.
|
|---|---|
|
Rate of Any Infections
|
2.80 infections per subject-year
|
SECONDARY outcome
Timeframe: approx. 12 month treatment periodPopulation: Full analysis set
The annual rate of nonserious infections was calculated as the number of nonserious infections per subject-year
Outcome measures
| Measure |
BT595
n=67 Participants
Subjects received BT595 (100 mg/mL human normal immunoglobulin) at doses between 0.2 and 0.8 g per kg body weight (bw) (2 to 8 mL/kg bw), either at a Q3W or Q4W schedule. The initial doses and dosage interval had to be consistent with the subject's prestudy IVIg treatment.
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|---|---|
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Rate of Nonserious Infections
|
2.74 infections per subject-year
|
SECONDARY outcome
Timeframe: approx. 12 month treatment periodPopulation: Full analysis set
Time to resolution of infections (days) was calculated as infection stop date - infection start date +1.
Outcome measures
| Measure |
BT595
n=67 Participants
Subjects received BT595 (100 mg/mL human normal immunoglobulin) at doses between 0.2 and 0.8 g per kg body weight (bw) (2 to 8 mL/kg bw), either at a Q3W or Q4W schedule. The initial doses and dosage interval had to be consistent with the subject's prestudy IVIg treatment.
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|---|---|
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Time to Resolution of Infections
|
7.0 days
Interval 7.0 to 8.0
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SECONDARY outcome
Timeframe: approx. 12 month treatment periodPopulation: Full analysis set
Median (min-max) number of days on antibiotics treatment per subject
Outcome measures
| Measure |
BT595
n=67 Participants
Subjects received BT595 (100 mg/mL human normal immunoglobulin) at doses between 0.2 and 0.8 g per kg body weight (bw) (2 to 8 mL/kg bw), either at a Q3W or Q4W schedule. The initial doses and dosage interval had to be consistent with the subject's prestudy IVIg treatment.
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|---|---|
|
Antibiotic Treatment Information
|
6.0 days
Interval 0.0 to 409.0
|
SECONDARY outcome
Timeframe: approx. 12 month treatment periodPopulation: Full analysis set
Annual rates of the number of days subjects are not able to attend school/work due to infections and their treatment will be calculated per subject-year.
Outcome measures
| Measure |
BT595
n=67 Participants
Subjects received BT595 (100 mg/mL human normal immunoglobulin) at doses between 0.2 and 0.8 g per kg body weight (bw) (2 to 8 mL/kg bw), either at a Q3W or Q4W schedule. The initial doses and dosage interval had to be consistent with the subject's prestudy IVIg treatment.
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|---|---|
|
Rate of Time Lost From School/Work Due to Infections
|
4.32 days per subject-year
|
SECONDARY outcome
Timeframe: approx. 12 month treatment periodPopulation: Full analysis set
Annual rates of the number of days of hospitalization (any hospitalization/ hospitalization due to infection) will be calculated per subject-year.
Outcome measures
| Measure |
BT595
n=67 Participants
Subjects received BT595 (100 mg/mL human normal immunoglobulin) at doses between 0.2 and 0.8 g per kg body weight (bw) (2 to 8 mL/kg bw), either at a Q3W or Q4W schedule. The initial doses and dosage interval had to be consistent with the subject's prestudy IVIg treatment.
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|---|---|
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Hospitalization / Hospitalization Due to Infection
Any Hospitalization
|
0.70 days per subject-year
|
|
Hospitalization / Hospitalization Due to Infection
Hospitalization due to Infection
|
0.36 days per subject-year
|
SECONDARY outcome
Timeframe: approx. 12 month treatment periodPopulation: Full analysis set
The number of days with episodes of fever will be calculated as the number of fever episodes per subject-year. Fever is defined as a body temperature ≥38°C (≥100.4°F).
Outcome measures
| Measure |
BT595
n=67 Participants
Subjects received BT595 (100 mg/mL human normal immunoglobulin) at doses between 0.2 and 0.8 g per kg body weight (bw) (2 to 8 mL/kg bw), either at a Q3W or Q4W schedule. The initial doses and dosage interval had to be consistent with the subject's prestudy IVIg treatment.
|
|---|---|
|
Fever Episodes
|
1.69 days per subject-year
|
Adverse Events
BT595
Serious events: 9 serious events
Other events: 63 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
BT595
n=67 participants at risk
Subjects received BT595 (100 mg/mL human normal immunoglobulin) at doses between 0.2 and 0.8 g per kg body weight (bw) (2 to 8 mL/kg bw), either at a Q3W or Q4W schedule. The initial doses and dosage interval had to be consistent with the subject's prestudy IVIg treatment.
|
|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
1.5%
1/67 • Number of events 1 • During treatment phase until Follow-up visit approx. 1 year
|
|
Hepatobiliary disorders
Hepatitis toxic
|
1.5%
1/67 • Number of events 1 • During treatment phase until Follow-up visit approx. 1 year
|
|
Immune system disorders
Anaphylactic reaction
|
1.5%
1/67 • Number of events 1 • During treatment phase until Follow-up visit approx. 1 year
|
|
Infections and infestations
Anal abscess
|
1.5%
1/67 • Number of events 1 • During treatment phase until Follow-up visit approx. 1 year
|
|
Infections and infestations
Appendicitis
|
1.5%
1/67 • Number of events 1 • During treatment phase until Follow-up visit approx. 1 year
|
|
Infections and infestations
Chronic sinusitis
|
1.5%
1/67 • Number of events 1 • During treatment phase until Follow-up visit approx. 1 year
|
|
Infections and infestations
Gastrointestinal viral infection
|
1.5%
1/67 • Number of events 1 • During treatment phase until Follow-up visit approx. 1 year
|
|
Injury, poisoning and procedural complications
Meniscus injury
|
1.5%
1/67 • Number of events 1 • During treatment phase until Follow-up visit approx. 1 year
|
|
Injury, poisoning and procedural complications
Thermal burn
|
1.5%
1/67 • Number of events 1 • During treatment phase until Follow-up visit approx. 1 year
|
|
Metabolism and nutrition disorders
Dehydration
|
1.5%
1/67 • Number of events 1 • During treatment phase until Follow-up visit approx. 1 year
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
1.5%
1/67 • Number of events 1 • During treatment phase until Follow-up visit approx. 1 year
|
|
Musculoskeletal and connective tissue disorders
Systemic scleroderma
|
1.5%
1/67 • Number of events 1 • During treatment phase until Follow-up visit approx. 1 year
|
Other adverse events
| Measure |
BT595
n=67 participants at risk
Subjects received BT595 (100 mg/mL human normal immunoglobulin) at doses between 0.2 and 0.8 g per kg body weight (bw) (2 to 8 mL/kg bw), either at a Q3W or Q4W schedule. The initial doses and dosage interval had to be consistent with the subject's prestudy IVIg treatment.
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
10.4%
7/67 • Number of events 8 • During treatment phase until Follow-up visit approx. 1 year
|
|
Gastrointestinal disorders
Nausea
|
6.0%
4/67 • Number of events 6 • During treatment phase until Follow-up visit approx. 1 year
|
|
Gastrointestinal disorders
Vomiting
|
6.0%
4/67 • Number of events 4 • During treatment phase until Follow-up visit approx. 1 year
|
|
General disorders
Fatigue
|
9.0%
6/67 • Number of events 10 • During treatment phase until Follow-up visit approx. 1 year
|
|
Infections and infestations
Bronchitis
|
11.9%
8/67 • Number of events 12 • During treatment phase until Follow-up visit approx. 1 year
|
|
Infections and infestations
Conjunctivitis
|
6.0%
4/67 • Number of events 6 • During treatment phase until Follow-up visit approx. 1 year
|
|
Infections and infestations
Influenza
|
9.0%
6/67 • Number of events 6 • During treatment phase until Follow-up visit approx. 1 year
|
|
Infections and infestations
Nasopharyngitis
|
23.9%
16/67 • Number of events 24 • During treatment phase until Follow-up visit approx. 1 year
|
|
Infections and infestations
Pharyngitis
|
10.4%
7/67 • Number of events 8 • During treatment phase until Follow-up visit approx. 1 year
|
|
Infections and infestations
Sinusitis
|
11.9%
8/67 • Number of events 11 • During treatment phase until Follow-up visit approx. 1 year
|
|
Infections and infestations
Upper respiratory tract infection
|
19.4%
13/67 • Number of events 24 • During treatment phase until Follow-up visit approx. 1 year
|
|
Infections and infestations
Urinary tract infection
|
9.0%
6/67 • Number of events 8 • During treatment phase until Follow-up visit approx. 1 year
|
|
Infections and infestations
Viral upper respiratory tract infection
|
10.4%
7/67 • Number of events 7 • During treatment phase until Follow-up visit approx. 1 year
|
|
Injury, poisoning and procedural complications
Extra dose administered
|
6.0%
4/67 • Number of events 4 • During treatment phase until Follow-up visit approx. 1 year
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.5%
5/67 • Number of events 5 • During treatment phase until Follow-up visit approx. 1 year
|
|
Nervous system disorders
Headache
|
25.4%
17/67 • Number of events 41 • During treatment phase until Follow-up visit approx. 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.0%
4/67 • Number of events 5 • During treatment phase until Follow-up visit approx. 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
9.0%
6/67 • Number of events 9 • During treatment phase until Follow-up visit approx. 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
7.5%
5/67 • Number of events 5 • During treatment phase until Follow-up visit approx. 1 year
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER