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A Multicenter Study to Evaluate the Efficacy and Safety of Cinryze® for the Treatment of Acute Antibody-mediated Rejection in Participants With Kidney Transplant

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ClinicalTrials.gov Identifier: NCT02547220
Recruitment Status : Terminated (Following a pre-scheduled interim analysis performed by the DMC, it was determined that the study met the pre-specified criteria for futility.)
First Posted : September 11, 2015
Results First Posted : July 13, 2020
Last Update Posted : July 13, 2020
Sponsor:
Information provided by (Responsible Party):
Takeda ( Shire )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Acute Antibody-Mediated Rejection (AMR)
Interventions Biological: Cinryze®
Drug: Placebo
Enrollment 39
Recruitment Details The study was conducted at 49 sites between 20 May 2016 (first participant first visit) and 31 May 2019 (last participant last visit).
Pre-assignment Details A total of 39 participants were randomized and received treatment.
Arm/Group Title Placebo CINRYZE
Hide Arm/Group Description Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of placebo (100 mL 0.9 percent [%] sodium chloride) on day 1 followed by 2500 units of placebo (100 mL 0.9% sodium chloride) on Days 3, 5, 7, 9, 11, and 13. Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of CINRYZE on Day 1 followed by 2500 units of CINRYZE in 100 mL of IV infusion on Day 3, 5, 7, 9, 11, and 13.
Period Title: Overall Study
Started 19 20
Completed 0 0
Not Completed 19 20
Reason Not Completed
Withdrawal by Subject             1             0
Study terminated by sponsor             18             20
Arm/Group Title Placebo CINRYZE Total
Hide Arm/Group Description Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of placebo (100 mL 0.9% sodium chloride) on day 1 followed by 2500 units of placebo (100 mL 0.9% sodium chloride) on Days 3, 5, 7, 9, 11, and 13. Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of CINRYZE on Day 1 followed by 2500 units of CINRYZE in 100 mL of IV infusion on Day 3, 5, 7, 9, 11, and 13. Total of all reporting groups
Overall Number of Baseline Participants 19 20 39
Hide Baseline Analysis Population Description
Full analysis set (FAS) consisted of all participants who had taken at least 1 dose of investigational product.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants 20 participants 39 participants
51.9  (12.49) 49.2  (13.45) 50.5  (12.90)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 20 participants 39 participants
Female
9
  47.4%
5
  25.0%
14
  35.9%
Male
10
  52.6%
15
  75.0%
25
  64.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 20 participants 39 participants
Hispanic or Latino
3
  15.8%
6
  30.0%
9
  23.1%
Not Hispanic or Latino
13
  68.4%
10
  50.0%
23
  59.0%
Unknown or Not Reported
3
  15.8%
4
  20.0%
7
  17.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 20 participants 39 participants
White
12
  63.2%
13
  65.0%
25
  64.1%
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian/Non-Japanese
5
  26.3%
1
   5.0%
6
  15.4%
Asian/Japanese
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
2
  10.0%
2
   5.1%
Black or African American
2
  10.5%
2
  10.0%
4
  10.3%
Latino
0
   0.0%
1
   5.0%
1
   2.6%
Unknown
0
   0.0%
1
   5.0%
1
   2.6%
1.Primary Outcome
Title Percentage of Participants With New or Worsening Transplant Glomerulopathy (TG) at Month 6 Post-Treatment
Hide Description New or worsening TG at month 6 by the standard score was defined as an increase in one or more between qualifying biopsy and 6-month biopsy. New or worsening TG was measured by Banff 2013 criteria (standard score) using allograft glomerulopathy (Cg0-Cg3): Cg0- No GBM double contours by light microscopy (LM) or electron microscopy (EM); Cg1- no GBM double contours by LM but GBM double contours in at least 3 glomerular capillaries by EM; Cg2- Double contours affecting 26 to 50% of peripheral capillary loops in the most affected of nonsclerotic glomeruli; Cg3- Double contours affecting more than 50% of peripheral capillary loops in the most affected of nonsclerotic glomeruli with a score range of 0 (no allograft glomerulopathy) and 3 (severe glomerulopathy). Percentage of participants with new or worsening TG at Month 6 post-treatment was reported.
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
FAS consisted of all participants who had taken at least 1 dose of investigational product.
Arm/Group Title Placebo CINRYZE
Hide Arm/Group Description:
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of placebo (100 mL 0.9% sodium chloride) on day 1 followed by 2500 units of placebo (100 mL 0.9% sodium chloride) on Days 3, 5, 7, 9, 11, and 13.
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of CINRYZE on Day 1 followed by 2500 units of CINRYZE in 100 mL of IV infusion on Day 3, 5, 7, 9, 11, and 13.
Overall Number of Participants Analyzed 19 20
Measure Type: Number
Unit of Measure: Percentage of participants
47.4 50.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, CINRYZE
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6857
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in percentage
Estimated Value 2.6
Confidence Interval (2-Sided) 95%
-29.4 to 34.5
Estimation Comments Difference in percentage was calculated by the difference in percentage of new or worsening TG at 6 months between CINRYZE and placebo
2.Secondary Outcome
Title Number of Participants With All-Cause Graft Failure at Month 48
Hide Description Graft failure was determined as the presence of one or more of the following criteria: institution of permanent dialysis (defined as dialysis treatment more than [>] 30 days), current transplant nephrectomy, and/or a clinical determination of cessation of kidney graft function and estimated glomerular filtration rate (eGFR) less than or equal to (<=) 15 milliliter (mL)/minute (min)/1.73 meter (m)^2.
Time Frame Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
This study was prematurely terminated at Month 36 due to futility issue. This outcome measure was planned to analyze at Month 48. Hence, data for this outcome measure was not collected as planned, analyzed and reported.
Arm/Group Title Placebo CINRYZE
Hide Arm/Group Description:
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of placebo (100 mL 0.9% sodium chloride) on day 1 followed by 2500 units of placebo (100 mL 0.9% sodium chloride) on Days 3, 5, 7, 9, 11, and 13.
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of CINRYZE on Day 1 followed by 2500 units of CINRYZE in 100 mL of IV infusion on Day 3, 5, 7, 9, 11, and 13.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Change From Baseline in Renal Function up to Month 48
Hide Description Renal function was measured as glomerular filtration rate calculated by the modification of diet in renal disease (eGFRMDRD).
Time Frame Baseline, up to Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
This study was prematurely terminated at Month 36 due to futility issue. This outcome measure was planned to analyze at Month 48. Hence, data for this outcome measure was not collected as planned, analyzed and reported.
Arm/Group Title Placebo CINRYZE
Hide Arm/Group Description:
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of placebo (100 mL 0.9% sodium chloride) on day 1 followed by 2500 units of placebo (100 mL 0.9% sodium chloride) on Days 3, 5, 7, 9, 11, and 13.
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of CINRYZE on Day 1 followed by 2500 units of CINRYZE in 100 mL of IV infusion on Day 3, 5, 7, 9, 11, and 13.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Change From Baseline With Pre-Antibody-Mediated Rejection (AMR) in Renal Function up to Month 48
Hide Description Renal function was measured as glomerular filtration rate calculated by the modification of diet in renal disease (eGFRMDRD). Pre-AMR baseline was the highest eGFRMDRD value obtained following the kidney transplant and within 30 days prior to the qualifying AMR episode.
Time Frame Pre-AMR Baseline, up to Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
This study was prematurely terminated at Month 36 due to futility issue. This outcome measure was planned to analyze at Month 48. Hence, data for this outcome measure was not collected as planned, analyzed and reported.
Arm/Group Title Placebo CINRYZE
Hide Arm/Group Description:
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of placebo (100 mL 0.9% sodium chloride) on day 1 followed by 2500 units of placebo (100 mL 0.9% sodium chloride) on Days 3, 5, 7, 9, 11, and 13.
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of CINRYZE on Day 1 followed by 2500 units of CINRYZE in 100 mL of IV infusion on Day 3, 5, 7, 9, 11, and 13.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Number of Participants With Proteinuria Levels at Month 48
Hide Description Proteinuria included spot urine protein, urine creatinine, and urine protein/urine creatinine ratio.
Time Frame Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
This study was prematurely terminated at Month 36 due to futility issue. This outcome measure was planned to analyze at Month 48. Hence, data for this outcome measure was not collected as planned, analyzed and reported.
Arm/Group Title Placebo CINRYZE
Hide Arm/Group Description:
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of placebo (100 mL 0.9% sodium chloride) on day 1 followed by 2500 units of placebo (100 mL 0.9% sodium chloride) on Days 3, 5, 7, 9, 11, and 13.
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of CINRYZE on Day 1 followed by 2500 units of CINRYZE in 100 mL of IV infusion on Day 3, 5, 7, 9, 11, and 13.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Change From Pre-Antibody-Mediated Rejection (AMR) Baseline in Histopathology Per Banff Criteria at Month 6
Hide Description Histopathological diagnosis of acute rejection was measured by Banff 2013 criteria: Glomerulitis score (g0-g3), allograft glomerulopathy (Cg0-cg3), Tubulitis score (T0-T3), Intimal arteritis score (V0-V3), peritubular capillaritis (PTC) (ptc0-ptc3) and Interstitial Inflammation score (i0-i3). The histopathology was a composite of the sub-scores. Each of the sub-scores or histopathology score ranges from 0 ( no histopathology) to 3 (more severe histopathology).
Time Frame Pre-AMR Baseline, Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
This study was prematurely terminated at Month 36 due to futility issues. The data of this secondary outcome measure was not collected as planned and the secondary analysis was not performed, due to early study termination.
Arm/Group Title Placebo CINRYZE
Hide Arm/Group Description:
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of placebo (100 mL 0.9% sodium chloride) on day 1 followed by 2500 units of placebo (100 mL 0.9% sodium chloride) on Days 3, 5, 7, 9, 11, and 13.
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of CINRYZE on Day 1 followed by 2500 units of CINRYZE in 100 mL of IV infusion on Day 3, 5, 7, 9, 11, and 13.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Number of Participants With All-Cause Graft Failure at Month 6
Hide Description Graft failure was determined by the presence of one or more of the following criteria: institution of permanent dialysis (defined as dialysis treatment more than [>] 30 days), current transplant nephrectomy, and/or a clinical determination of cessation of kidney graft function and estimated glomerular filtration rate (eGFR) less than or equal to (<=) 15 milliliter (mL)/minute (min)/1.73 meter (m)^2.
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
This study was prematurely terminated at Month 36 due to futility issues. The data of this secondary outcome measure was not collected as planned and the secondary analysis was not performed, due to early study termination.
Arm/Group Title Placebo CINRYZE
Hide Arm/Group Description:
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of placebo (100 mL 0.9% sodium chloride) on day 1 followed by 2500 units of placebo (100 mL 0.9% sodium chloride) on Days 3, 5, 7, 9, 11, and 13.
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of CINRYZE on Day 1 followed by 2500 units of CINRYZE in 100 mL of IV infusion on Day 3, 5, 7, 9, 11, and 13.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Number of Participants With Graft Failure Due to Antibody-Mediated Rejection (AMR) Episodes at Month 48
Hide Description Graft failure was determined by the presence of one or more of the following criteria: institution of permanent dialysis (defined as dialysis treatment more than [>] 30 days), current transplant nephrectomy, and/or a clinical determination of cessation of kidney graft function and estimated glomerular filtration rate (eGFR) less than or equal to (<=) 15 milliliter (mL)/minute (min)/1.73 meter (m)^2.
Time Frame Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
This study was prematurely terminated at Month 36 due to futility issue. This outcome measure was planned to analyze at Month 48. Hence, data for this outcome measure was not collected as planned, analyzed and reported.
Arm/Group Title Placebo CINRYZE
Hide Arm/Group Description:
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of placebo (100 mL 0.9% sodium chloride) on day 1 followed by 2500 units of placebo (100 mL 0.9% sodium chloride) on Days 3, 5, 7, 9, 11, and 13.
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of CINRYZE on Day 1 followed by 2500 units of CINRYZE in 100 mL of IV infusion on Day 3, 5, 7, 9, 11, and 13.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Time to All-Cause Graft Failure up to Month 48
Hide Description Graft failure was determined by the presence of one or more of the following criteria: institution of permanent dialysis (defined as dialysis treatment more than [>] 30 days), current transplant nephrectomy, and/or a clinical determination of cessation of kidney graft function and estimated glomerular filtration rate (eGFR) less than or equal to (<=) 15 milliliter (mL)/minute (min)/1.73 meter (m)^2. Time to all-cause graft failure in months was calculated as (Date of graft failure - Date of first dose + 1)/30.25.
Time Frame Up to Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
This study was prematurely terminated at Month 36 due to futility issue. This outcome measure was planned to analyze at Month 48. Hence, data for this outcome measure was not collected as planned, analyzed and reported.
Arm/Group Title Placebo CINRYZE
Hide Arm/Group Description:
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of placebo (100 mL 0.9% sodium chloride) on day 1 followed by 2500 units of placebo (100 mL 0.9% sodium chloride) on Days 3, 5, 7, 9, 11, and 13.
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of CINRYZE on Day 1 followed by 2500 units of CINRYZE in 100 mL of IV infusion on Day 3, 5, 7, 9, 11, and 13.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Time to Graft Failure Due to Antibody-Mediated Rejection (AMR) Episodes up to Month 48
Hide Description Graft failure was determined by the presence of one or more of the following criteria: institution of permanent dialysis (defined as dialysis treatment > 30 days), current transplant nephrectomy, and/or a clinical determination of cessation of kidney graft function and eGFR <=15 mL/ min/1.73m^2. Time to graft failure due to AMR episodes in months was calculated as (Date of graft failure due to AMR - Date of first dose + 1)/30.25.
Time Frame Up to Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
This study was prematurely terminated at Month 36 due to futility issue. This outcome measure was planned to analyze at Month 48. Hence, data for this outcome measure was not collected as planned, analyzed and reported.
Arm/Group Title Placebo CINRYZE
Hide Arm/Group Description:
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of placebo (100 mL 0.9% sodium chloride) on day 1 followed by 2500 units of placebo (100 mL 0.9% sodium chloride) on Days 3, 5, 7, 9, 11, and 13.
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of CINRYZE on Day 1 followed by 2500 units of CINRYZE in 100 mL of IV infusion on Day 3, 5, 7, 9, 11, and 13.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
11.Secondary Outcome
Title Number of Participants With Resolution of the Qualifying Antibody-Mediated Rejection (AMR) Episodes at Month 48
Hide Description Number of participants with resolution of the qualifying AMR episodes at Month 48.
Time Frame Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
This study was prematurely terminated at Month 36 due to futility issue. This outcome measure was planned to analyze at Month 48. Hence, data for this outcome measure was not collected as planned, analyzed and reported.
Arm/Group Title Placebo CINRYZE
Hide Arm/Group Description:
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of placebo (100 mL 0.9% sodium chloride) on day 1 followed by 2500 units of placebo (100 mL 0.9% sodium chloride) on Days 3, 5, 7, 9, 11, and 13.
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of CINRYZE on Day 1 followed by 2500 units of CINRYZE in 100 mL of IV infusion on Day 3, 5, 7, 9, 11, and 13.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title Time to Resolution of Qualifying Antibody-Mediated Rejection (AMR) Episodes up to Month 48
Hide Description Time to resolution of qualifying AMR episodes was calculated as (Date of qualifying AMR resolution - Date of first dose + 1)/30.25. Participants who didn't had resolution of qualifying AMR episodes and still on-study were censored at the date of last visit; Participants who had completed the study without resolution of qualifying AMR were censored at the date of study completion; participants who discontinued from the study without resolution of qualifying AMR were censored at the date of early discontinuation.
Time Frame Up to Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
This study was prematurely terminated at Month 36 due to futility issue. This outcome measure was planned to analyze at Month 48. Hence, data for this outcome measure was not collected as planned, analyzed and reported.
Arm/Group Title Placebo CINRYZE
Hide Arm/Group Description:
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of placebo (100 mL 0.9% sodium chloride) on day 1 followed by 2500 units of placebo (100 mL 0.9% sodium chloride) on Days 3, 5, 7, 9, 11, and 13.
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of CINRYZE on Day 1 followed by 2500 units of CINRYZE in 100 mL of IV infusion on Day 3, 5, 7, 9, 11, and 13.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
13.Secondary Outcome
Title Number of Participants Who Were Alive at Month 36
Hide Description Number of participants who were alive at Month 36 (study terminated instead of Month 48) were reported.
Time Frame Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set consisted of all participants who had taken at least 1 dose of investigational product. This study was prematurely terminated at Month 36 due to futility issue. This outcome measure was planned to analyze at Month 48.
Arm/Group Title Placebo CINRYZE
Hide Arm/Group Description:
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of placebo (100 mL 0.9% sodium chloride) on day 1 followed by 2500 units of placebo (100 mL 0.9% sodium chloride) on Days 3, 5, 7, 9, 11, and 13.
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of CINRYZE on Day 1 followed by 2500 units of CINRYZE in 100 mL of IV infusion on Day 3, 5, 7, 9, 11, and 13.
Overall Number of Participants Analyzed 19 20
Measure Type: Count of Participants
Unit of Measure: Participants
19
 100.0%
20
 100.0%
14.Secondary Outcome
Title Time to All-Cause Mortality up to Month 48
Hide Description Time to all-cause mortality was calculated as (Date of discontinuation due to death - Date of first dose + 1)/30.25. Participants who are alive and still on-study were censored at the date of last visit; Participants who had completed the study were censored at the date of study completion; Participants who discontinued from the study but not due to death were censored at the date of early discontinuation.
Time Frame Up to Month 48
Hide Outcome Measure Data
Hide Analysis Population Description
This study was prematurely terminated at Month 36 due to futility issue. This outcome measure was planned to analyze at Month 48. Hence, data for this outcome measure was not collected as planned, analyzed and reported.
Arm/Group Title Placebo CINRYZE
Hide Arm/Group Description:
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of placebo (100 mL 0.9% sodium chloride) on day 1 followed by 2500 units of placebo (100 mL 0.9% sodium chloride) on Days 3, 5, 7, 9, 11, and 13.
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of CINRYZE on Day 1 followed by 2500 units of CINRYZE in 100 mL of IV infusion on Day 3, 5, 7, 9, 11, and 13.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
15.Secondary Outcome
Title Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Hide Description An adverse event (AE) was any untoward, undesired, unplanned clinical event in the form of signs, symptoms, disease, or laboratory or physiological observations occurred in a participant participating in a clinical study with the sponsor's product, regardless of causal relationship. TEAEs were defined as events that started or worsened on or after the date of the first dose of investigational product, but no later than 30 days following the last dose of investigational product, within a treatment period.
Time Frame From start of study drug administration up to study termination (Month 36)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set consisted of all participants who had taken at least 1 dose of investigational product.
Arm/Group Title Placebo CINRYZE
Hide Arm/Group Description:
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of placebo (100 mL 0.9% sodium chloride) on day 1 followed by 2500 units of placebo (100 mL 0.9% sodium chloride) on Days 3, 5, 7, 9, 11, and 13.
Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of CINRYZE on Day 1 followed by 2500 units of CINRYZE in 100 mL of IV infusion on Day 3, 5, 7, 9, 11, and 13.
Overall Number of Participants Analyzed 19 20
Measure Type: Count of Participants
Unit of Measure: Participants
16
  84.2%
16
  80.0%
Time Frame From start of study drug administration up to study termination (Month 36)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo CINRYZE
Hide Arm/Group Description Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of placebo (100 mL 0.9% sodium chloride) on day 1 followed by 2500 units of placebo (100 mL 0.9% sodium chloride) on Days 3, 5, 7, 9, 11, and 13. Participants received a total of seven doses with an initial 100 mL intravenous (IV) infusion containing 5000 units of CINRYZE on Day 1 followed by 2500 units of CINRYZE in 100 mL of IV infusion on Day 3, 5, 7, 9, 11, and 13.
All-Cause Mortality
Placebo CINRYZE
Affected / at Risk (%) Affected / at Risk (%)
Total   0/19 (0.00%)      0/20 (0.00%)    
Hide Serious Adverse Events
Placebo CINRYZE
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/19 (31.58%)      3/20 (15.00%)    
Gastrointestinal disorders     
Gastrointestinal haemorrhage * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
General disorders     
Catheter site thrombosis * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Immune system disorders     
Anaphylactic shock * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Infections and infestations     
Klebsiella sepsis * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Pneumonia * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Injury, poisoning and procedural complications     
Arteriovenous fistula thrombosis * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Renal and urinary disorders     
Renal impairment * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Pulmonary oedema * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
1
Term from vocabulary, MedDRA 20.1
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo CINRYZE
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/19 (78.95%)      16/20 (80.00%)    
Blood and lymphatic system disorders     
Anaemia * 1  2/19 (10.53%)  2 0/20 (0.00%)  0
Leukopenia * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Thrombocytopenia * 1  0/19 (0.00%)  0 2/20 (10.00%)  2
Cardiac disorders     
Bradycardia * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Gastrointestinal disorders     
Abdominal pain * 1  1/19 (5.26%)  1 1/20 (5.00%)  1
Constipation * 1  2/19 (10.53%)  2 0/20 (0.00%)  0
Diarrhoea * 1  2/19 (10.53%)  2 1/20 (5.00%)  1
Dry mouth * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Flatulence * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Nausea * 1  2/19 (10.53%)  2 1/20 (5.00%)  1
Oesophagitis * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Tooth disorder * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Vomiting * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
General disorders     
Asthenia * 1  2/19 (10.53%)  2 1/20 (5.00%)  1
Fatigue * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Malaise * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Nodule * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Non-cardiac chest pain * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Oedema peripheral * 1  2/19 (10.53%)  2 0/20 (0.00%)  0
Infections and infestations     
BK virus infection * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Catheter site infection * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Clostridium difficile colitis * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Cytomegalovirus infection * 1  1/19 (5.26%)  1 1/20 (5.00%)  1
Peritonitis * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Upper respiratory tract infection * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Urinary tract infection bacterial * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Urosepsis * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Injury, poisoning and procedural complications     
Arteriovenous fistula site haematoma * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Citrate toxicity * 1  0/19 (0.00%)  0 1/20 (5.00%)  5
Complications of transplanted kidney * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Post procedural haemorrhage * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Toxicity to various agents * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Vascular access complication * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Investigations     
Alanine aminotransferase increased * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Aspartate aminotransferase increased * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Blood bicarbonate decreased * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Blood bicarbonate increased * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Blood creatinine increased * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Blood glucose increased * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Blood magnesium decreased * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Blood phosphorus decreased * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Blood potassium increased * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Blood urea increased * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Blood uric acid increased * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Glomerular filtration rate decreased * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Haemoglobin decreased * 1  2/19 (10.53%)  2 0/20 (0.00%)  0
Neutrophil count increased * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
White blood cell count increased * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Metabolism and nutrition disorders     
Diabetes mellitus * 1  0/19 (0.00%)  0 2/20 (10.00%)  2
Folate deficiency * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Hyperglycaemia * 1  1/19 (5.26%)  1 1/20 (5.00%)  1
Hyperkalaemia * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Hypokalaemia * 1  2/19 (10.53%)  2 0/20 (0.00%)  0
Hypomagnesaemia * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Hypophosphataemia * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Metabolic acidosis * 1  1/19 (5.26%)  1 1/20 (5.00%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Muscle spasms * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Neck pain * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Nervous system disorders     
Dizziness * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Headache * 1  1/19 (5.26%)  3 0/20 (0.00%)  0
Hypoaesthesia * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Tremor * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Psychiatric disorders     
Anxiety * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Renal and urinary disorders     
Acute kidney injury * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Chronic kidney disease * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Proteinuria * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Respiratory, thoracic and mediastinal disorders     
Dry throat * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Epistaxis * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Oropharyngeal pain * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Sinus disorder * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
Throat irritation * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Skin and subcutaneous tissue disorders     
Hyperhidrosis * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Rash pruritic * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Urticaria * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Vascular disorders     
Hypertension * 1  2/19 (10.53%)  3 1/20 (5.00%)  2
Lymphocele * 1  0/19 (0.00%)  0 1/20 (5.00%)  1
Orthostatic hypotension * 1  1/19 (5.26%)  1 0/20 (0.00%)  0
1
Term from vocabulary, MedDRA 20.1
*
Indicates events were collected by non-systematic assessment
This study was prematurely terminated at Month 36 due to futility issue.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Shire
Phone: +1 866 842 5335
EMail: ClinicalTransparency@takeda.com
Layout table for additonal information
Responsible Party: Takeda ( Shire )
ClinicalTrials.gov Identifier: NCT02547220    
Other Study ID Numbers: SHP616-302
2015-000726-11 ( EudraCT Number )
First Submitted: September 2, 2015
First Posted: September 11, 2015
Results First Submitted: May 29, 2020
Results First Posted: July 13, 2020
Last Update Posted: July 13, 2020