Trial Outcomes & Findings for Efficacy and Safety of Human Plasma-derived C1-esterase Inhibitor as add-on to Standard of Care for the Treatment of Refractory Antibody Mediated Rejection (AMR) in Adult Renal Transplant Recipients (NCT NCT03221842)
NCT ID: NCT03221842
Last Updated: 2022-07-29
Results Overview
Loss of response is defined as 1 of the following, whichever occurs first: * Decline in Estimated Glomerular Filtration Rate (eGFR), or * Allograft failure, or * Subject death by any cause.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
63 participants
Primary outcome timeframe
Up to 38 weeks
Results posted on
2022-07-29
Participant Flow
Only 13 participants that completed Period 1 were eligible to continue to Period 2. Eligibility based on the amendment in place at the time the subject completed Period 1.
Participant milestones
| Measure |
C1-INH
C1-esterase inhibitor (CSL842)
C1-esterase inhibitor: C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution administered at a dose of 60 IU/kg
|
Placebo
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
|---|---|---|
|
Period 1 (Open-label)
STARTED
|
63
|
0
|
|
Period 1 (Open-label)
COMPLETED
|
53
|
0
|
|
Period 1 (Open-label)
NOT COMPLETED
|
10
|
0
|
|
Period 2 (Randomized, Blinded)
STARTED
|
7
|
6
|
|
Period 2 (Randomized, Blinded)
COMPLETED
|
6
|
5
|
|
Period 2 (Randomized, Blinded)
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
C1-INH
C1-esterase inhibitor (CSL842)
C1-esterase inhibitor: C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution administered at a dose of 60 IU/kg
|
Placebo
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
|---|---|---|
|
Period 1 (Open-label)
Adverse Event
|
4
|
0
|
|
Period 1 (Open-label)
Physician Decision
|
2
|
0
|
|
Period 1 (Open-label)
Lost to Follow-up
|
1
|
0
|
|
Period 1 (Open-label)
Terminated by sponsor
|
1
|
0
|
|
Period 1 (Open-label)
Other
|
2
|
0
|
|
Period 2 (Randomized, Blinded)
Death
|
0
|
1
|
|
Period 2 (Randomized, Blinded)
Lack of Efficacy
|
1
|
0
|
Baseline Characteristics
Efficacy and Safety of Human Plasma-derived C1-esterase Inhibitor as add-on to Standard of Care for the Treatment of Refractory Antibody Mediated Rejection (AMR) in Adult Renal Transplant Recipients
Baseline characteristics by cohort
| Measure |
C1-INH
n=63 Participants
C1-esterase inhibitor (CSL842)
C1-esterase inhibitor: C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution administered at a dose of 60 IU/kg
|
|---|---|
|
Age, Continuous
|
43.3 years
STANDARD_DEVIATION 13.83 • n=5 Participants
|
|
Age, Customized
>=18 and <65 years
|
57 participants
n=5 Participants
|
|
Age, Customized
>=65 years
|
6 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
36 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
52 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
5 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
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
39 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
6 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 38 weeksPopulation: Modified Intent-to-Treat Analysis Set (mITT) - All subjects randomized under the original protocol and under all protocol amendments were included in this population except the subjects randomized prior to Amendment 3 who did not satisfy the responder criteria updated in Amendment 3.
Loss of response is defined as 1 of the following, whichever occurs first: * Decline in Estimated Glomerular Filtration Rate (eGFR), or * Allograft failure, or * Subject death by any cause.
Outcome measures
| Measure |
C1-INH
n=6 Participants
C1-esterase inhibitor (CSL842)
C1-esterase inhibitor: C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution administered at a dose of 60 IU/kg
|
Placebo
n=5 Participants
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
Placebo
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
|---|---|---|---|
|
Percent of Participants With Loss-of-response During Treatment Period 2 (TP2)
|
33.3 percentage of participants
|
40.0 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Up to 38 weeksPopulation: mITT
Allograft failure is defined as 1 of the following: * Allograft nephrectomy, institution of permanent dialysis, or return to the transplant waitlist for renal transplant, whichever occurs first, OR * Subject death by any cause
Outcome measures
| Measure |
C1-INH
n=6 Participants
C1-esterase inhibitor (CSL842)
C1-esterase inhibitor: C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution administered at a dose of 60 IU/kg
|
Placebo
n=5 Participants
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
Placebo
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
|---|---|---|---|
|
Number of Participants With All-cause Allograft Failure During TP2
|
0 number of participants
|
1 number of participants
|
—
|
SECONDARY outcome
Timeframe: Up to 38 weeksPopulation: mITT
Outcome measures
| Measure |
C1-INH
n=6 Participants
C1-esterase inhibitor (CSL842)
C1-esterase inhibitor: C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution administered at a dose of 60 IU/kg
|
Placebo
n=5 Participants
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
Placebo
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
|---|---|---|---|
|
Percent of Participants With All-cause Allograft Failure During TP2
|
0 percentage of participants
|
20 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Baseline and 13 weeksPopulation: The Run-in Safety (RiS) analysis set comprised all subjects who received at least 1 dose of C1-INH during TP1.
Outcome measures
| Measure |
C1-INH
n=63 Participants
C1-esterase inhibitor (CSL842)
C1-esterase inhibitor: C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution administered at a dose of 60 IU/kg
|
Placebo
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
Placebo
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
|---|---|---|---|
|
Absolute Change From Baseline in Estimated Glomerular Filtration Rate at End of Treatment Period 1 (TP1)
|
-0.75 mL/min/1.73m^2
Interval -17.0 to 7.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and 38 weeksPopulation: mITT
Outcome measures
| Measure |
C1-INH
n=6 Participants
C1-esterase inhibitor (CSL842)
C1-esterase inhibitor: C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution administered at a dose of 60 IU/kg
|
Placebo
n=4 Participants
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
Placebo
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
|---|---|---|---|
|
Absolute Change From Baseline in Estimated Glomerular Filtration Rate at End of TP2
|
7.75 mL/min/1.73m^2
Standard Deviation 8.454
|
15.25 mL/min/1.73m^2
Standard Deviation 10.444
|
—
|
SECONDARY outcome
Timeframe: Up to 38 weeksPopulation: The Sponsor terminated the study due to futility of enrolment. Because of the study termination, limited efficacy results are presented in this report. Due to study termination, data was not collected for this endpoint.
The Sponsor terminated the study due to futility of enrolment. Because of the study termination, limited efficacy results are presented in this report.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to approximately 208 weeksPopulation: The Sponsor terminated the study due to futility of enrolment. Because of the study termination, limited efficacy results are presented in this report. Due to study termination, data was not collected for this endpoint.
The Sponsor terminated the study due to futility of enrolment. Because of the study termination, limited efficacy results are presented in this report.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 13 weeksPopulation: RiS
Responders were defined as subjects whose End-of-TP1 eGFR was ≥ 90% of baseline eGFR and ≥ 20 mL/min/1.73 m2.
Outcome measures
| Measure |
C1-INH
n=63 Participants
C1-esterase inhibitor (CSL842)
C1-esterase inhibitor: C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution administered at a dose of 60 IU/kg
|
Placebo
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
Placebo
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
|---|---|---|---|
|
Number of Responders at the End-of-TP1
|
33 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 13 weeksPopulation: RiS
Responders were defined as subjects whose End-of-TP1 eGFR was ≥ 90% of baseline eGFR and ≥ 20 mL/min/1.73 m2.
Outcome measures
| Measure |
C1-INH
n=63 Participants
C1-esterase inhibitor (CSL842)
C1-esterase inhibitor: C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution administered at a dose of 60 IU/kg
|
Placebo
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
Placebo
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
|---|---|---|---|
|
Percent of Responders at the End-of-TP1
|
52.4 percentage of responders
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to approximately 208 weeksPopulation: The Sponsor terminated the study due to futility of enrolment. Because of the study termination, limited efficacy results are presented in this report. Due to study termination, data was not collected for this endpoint.
The Sponsor terminated the study due to futility of enrolment. Because of the study termination, limited efficacy results are presented in this report.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to approximately 42 weeks after the time of first investigational product administrationPopulation: RiS and RWS \[The Randomized Withdrawal Safety (RWS) analysis set included all subjects in the ITT analysis set who received at least 1 dose of the investigational product after randomization during TP2\]
Outcome measures
| Measure |
C1-INH
n=63 Participants
C1-esterase inhibitor (CSL842)
C1-esterase inhibitor: C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution administered at a dose of 60 IU/kg
|
Placebo
n=7 Participants
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
Placebo
n=6 Participants
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
|---|---|---|---|
|
Percent of Participants With Any Adverse Event (AE) Assessed as Related to Investigational Product
|
20.6 percentage of participants
|
0 percentage of participants
|
16.7 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 13 weeksPopulation: The pharmacokinetic analysis set (PK) comprised all subjects who consented to provide rich PK sampling, who received ≥ 1 dose of C1-INH, and who had ≥ 1 measurable level of C1-INH functional activity. (some participants had missing data) or C1-INH antigen concentration.
C1-esterase Inhibitor may play a role in the prevention of antibody-mediated rejection (AMR) following kidney transplant. Low levels of C1 esterase inhibitor concentration and its functional activity may lead to AMR. Patients with AMR may go on to lose their kidney transplant and have other associated health risks. Levels of C1-esterase inhibitor functional activity in plasma is described as a percent.
Outcome measures
| Measure |
C1-INH
n=20 Participants
C1-esterase inhibitor (CSL842)
C1-esterase inhibitor: C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution administered at a dose of 60 IU/kg
|
Placebo
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
Placebo
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
|---|---|---|---|
|
Mean Pre-dose C1-esterase Inhibitor Functional Activity
week 2
|
168.86 percent functional activity
Standard Deviation 64.059
|
—
|
—
|
|
Mean Pre-dose C1-esterase Inhibitor Functional Activity
week 11
|
179.32 percent functional activity
Standard Deviation 58.551
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 72 hours after post-dose on Day 10 and on Day 77 of Period 1Population: PK (some participants had missing data)
C1-esterase Inhibitor may play a role in the prevention of antibody-mediated rejection (AMR) following kidney transplant. Low levels of C1 esterase inhibitor concentration and its functional activity may lead to AMR. Patients with AMR may go on to lose their kidney transplant and have other associated health risks. Levels of C1-esterase inhibitor functional activity is described as a percent.
Outcome measures
| Measure |
C1-INH
n=15 Participants
C1-esterase inhibitor (CSL842)
C1-esterase inhibitor: C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution administered at a dose of 60 IU/kg
|
Placebo
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
Placebo
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
|---|---|---|---|
|
Area Under the Plasma Concentration Time Curve (AUC0-t) for C1-INH Functional Activity
Day 10
|
15229.84819 hours*percent functional activity
Standard Deviation 4149.16754
|
—
|
—
|
|
Area Under the Plasma Concentration Time Curve (AUC0-t) for C1-INH Functional Activity
Day 77
|
12742.20883 hours*percent functional activity
Standard Deviation 4445.31881
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 72 hours after post-dose on Day 10 and on Day 77 of Period 1Population: PK (some participants had missing data)
Outcome measures
| Measure |
C1-INH
n=15 Participants
C1-esterase inhibitor (CSL842)
C1-esterase inhibitor: C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution administered at a dose of 60 IU/kg
|
Placebo
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
Placebo
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
|---|---|---|---|
|
Time to Maximum Plasma Concentration (Tmax) for C1-INH Functional Activity
Day 10
|
9.9298 hours
Standard Deviation 16.3288
|
—
|
—
|
|
Time to Maximum Plasma Concentration (Tmax) for C1-INH Functional Activity
Day 77
|
37.9251 hours
Standard Deviation 22.8543
|
—
|
—
|
Adverse Events
C1-INH (Period 1)
Serious events: 25 serious events
Other events: 46 other events
Deaths: 0 deaths
C1-INH (Period 2)
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Placebo (Period 2)
Serious events: 3 serious events
Other events: 5 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
C1-INH (Period 1)
n=63 participants at risk
C1-esterase inhibitor (CSL842)
C1-esterase inhibitor: C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution administered at a dose of 60 IU/kg
|
C1-INH (Period 2)
n=7 participants at risk
C1-esterase inhibitor (CSL842)
C1-esterase inhibitor: C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution administered at a dose of 60 IU/kg
|
Placebo (Period 2)
n=6 participants at risk
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
|---|---|---|---|
|
Investigations
Blood creatine increased
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts
|
0.00%
0/63 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
16.7%
1/6 • Number of events 1 • Up to 42 weeks per participant
|
|
Immune system disorders
Transplant rejection
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
16.7%
1/6 • Number of events 1 • Up to 42 weeks per participant
|
|
Blood and lymphatic system disorders
Anaemia
|
3.2%
2/63 • Number of events 2 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
General disorders
Pyrexia
|
3.2%
2/63 • Number of events 2 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
General disorders
Hypothermia
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
General disorders
Unevaluable event
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Gastrointestinal disorders
Vomiting
|
4.8%
3/63 • Number of events 3 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Gastrointestinal disorders
Nausea
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Hepatobiliary disorders
Cholecystitis acute
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Renal and urinary disorders
Acute kidney injury
|
3.2%
2/63 • Number of events 2 • Up to 42 weeks per participant
|
14.3%
1/7 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Renal and urinary disorders
Nephrotic syndrome
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Renal and urinary disorders
Perinephric collection
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Renal and urinary disorders
Pyelocaliectasis
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Renal and urinary disorders
Renal failure
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Renal and urinary disorders
Urinary tract obstruction
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Infections and infestations
Gastroenteritis
|
4.8%
3/63 • Number of events 3 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Infections and infestations
Pneumonia
|
3.2%
2/63 • Number of events 2 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Infections and infestations
Appendicitis
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Infections and infestations
Bacteraemia
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Infections and infestations
Bacterial pyelonephritis
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Infections and infestations
Erysipelas
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Infections and infestations
Pneumocystis jirovecii pneumonia
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Infections and infestations
Pseudomonal sepsis
|
0.00%
0/63 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
16.7%
1/6 • Number of events 1 • Up to 42 weeks per participant
|
|
Infections and infestations
Rhinovirus infection
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Infections and infestations
Upper respiratory tract infection
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Infections and infestations
Urethritis
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Infections and infestations
Wound infection pseudomonas
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
Other adverse events
| Measure |
C1-INH (Period 1)
n=63 participants at risk
C1-esterase inhibitor (CSL842)
C1-esterase inhibitor: C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution administered at a dose of 60 IU/kg
|
C1-INH (Period 2)
n=7 participants at risk
C1-esterase inhibitor (CSL842)
C1-esterase inhibitor: C1-esterase inhibitor is a human plasma-derived lyophilised powder for reconstitution administered at a dose of 60 IU/kg
|
Placebo (Period 2)
n=6 participants at risk
Excipients of C1-INH plus albumin
Placebo: Excipients of C1-INH plus albumin
|
|---|---|---|---|
|
Vascular disorders
Hypertension
|
9.5%
6/63 • Number of events 7 • Up to 42 weeks per participant
|
14.3%
1/7 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Refractory cytopenia with unilineage dysplasia
|
0.00%
0/63 • Up to 42 weeks per participant
|
14.3%
1/7 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
General disorders
Asthenia
|
6.3%
4/63 • Number of events 4 • Up to 42 weeks per participant
|
14.3%
1/7 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
General disorders
Discomfort
|
0.00%
0/63 • Up to 42 weeks per participant
|
14.3%
1/7 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
General disorders
Oedema
|
12.7%
8/63 • Number of events 9 • Up to 42 weeks per participant
|
14.3%
1/7 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
General disorders
Pain
|
3.2%
2/63 • Number of events 4 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
16.7%
1/6 • Number of events 1 • Up to 42 weeks per participant
|
|
General disorders
Pyrexia
|
7.9%
5/63 • Number of events 5 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Injury, poisoning and procedural complications
Procedural pain
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
16.7%
1/6 • Number of events 1 • Up to 42 weeks per participant
|
|
Cardiac disorders
Palpitations
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
16.7%
1/6 • Number of events 1 • Up to 42 weeks per participant
|
|
Blood and lymphatic system disorders
Anaemia
|
12.7%
8/63 • Number of events 9 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Blood and lymphatic system disorders
Leukopenia
|
7.9%
5/63 • Number of events 7 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/63 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
16.7%
1/6 • Number of events 1 • Up to 42 weeks per participant
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.3%
4/63 • Number of events 4 • Up to 42 weeks per participant
|
14.3%
1/7 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.9%
5/63 • Number of events 6 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
3.2%
2/63 • Number of events 10 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
16.7%
1/6 • Number of events 1 • Up to 42 weeks per participant
|
|
Nervous system disorders
Burning sensation
|
0.00%
0/63 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
16.7%
1/6 • Number of events 1 • Up to 42 weeks per participant
|
|
Nervous system disorders
Headache
|
28.6%
18/63 • Number of events 32 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/63 • Up to 42 weeks per participant
|
14.3%
1/7 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Gastrointestinal disorders
Anal pruritus
|
0.00%
0/63 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
16.7%
1/6 • Number of events 1 • Up to 42 weeks per participant
|
|
Gastrointestinal disorders
Diarrhoea
|
17.5%
11/63 • Number of events 23 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Gastrointestinal disorders
Nausea
|
14.3%
9/63 • Number of events 12 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
16.7%
1/6 • Number of events 1 • Up to 42 weeks per participant
|
|
Gastrointestinal disorders
Vomiting
|
17.5%
11/63 • Number of events 13 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Hepatobiliary disorders
Hepatocellular injury
|
7.9%
5/63 • Number of events 5 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Renal and urinary disorders
Acute kidney injury
|
9.5%
6/63 • Number of events 6 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Renal and urinary disorders
Focal segmental glomerulosclerosis
|
0.00%
0/63 • Up to 42 weeks per participant
|
14.3%
1/7 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
3.2%
2/63 • Number of events 2 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
16.7%
1/6 • Number of events 1 • Up to 42 weeks per participant
|
|
Skin and subcutaneous tissue disorders
Dermatitis papillaris capillitii
|
0.00%
0/63 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
16.7%
1/6 • Number of events 1 • Up to 42 weeks per participant
|
|
Metabolism and nutrition disorders
Folate deficiency
|
1.6%
1/63 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
16.7%
1/6 • Number of events 1 • Up to 42 weeks per participant
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
4.8%
3/63 • Number of events 3 • Up to 42 weeks per participant
|
14.3%
1/7 • Number of events 1 • Up to 42 weeks per participant
|
16.7%
1/6 • Number of events 1 • Up to 42 weeks per participant
|
|
Metabolism and nutrition disorders
Hyperphosphataemia
|
0.00%
0/63 • Up to 42 weeks per participant
|
14.3%
1/7 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
6.3%
4/63 • Number of events 4 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
7.9%
5/63 • Number of events 6 • Up to 42 weeks per participant
|
14.3%
1/7 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Infections and infestations
Body tinea
|
0.00%
0/63 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
16.7%
1/6 • Number of events 1 • Up to 42 weeks per participant
|
|
Infections and infestations
Conjunctivitis viral
|
0.00%
0/63 • Up to 42 weeks per participant
|
14.3%
1/7 • Number of events 1 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Infections and infestations
Cytomegalovirus infection
|
4.8%
3/63 • Number of events 3 • Up to 42 weeks per participant
|
14.3%
1/7 • Number of events 2 • Up to 42 weeks per participant
|
0.00%
0/6 • Up to 42 weeks per participant
|
|
Infections and infestations
Staphylococcal infection
|
0.00%
0/63 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
16.7%
1/6 • Number of events 1 • Up to 42 weeks per participant
|
|
Infections and infestations
Trichomoniasis
|
0.00%
0/63 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
16.7%
1/6 • Number of events 1 • Up to 42 weeks per participant
|
|
Infections and infestations
Urinary tract infection
|
3.2%
2/63 • Number of events 2 • Up to 42 weeks per participant
|
0.00%
0/7 • Up to 42 weeks per participant
|
16.7%
1/6 • Number of events 1 • Up to 42 weeks per participant
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place