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Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks in Patients With Hereditary Angioedema

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ClinicalTrials.gov Identifier: NCT00262301
Recruitment Status : Completed
First Posted : December 6, 2005
Results First Posted : August 30, 2012
Last Update Posted : October 2, 2012
Sponsor:
Information provided by (Responsible Party):
Pharming Technologies B.V.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Hereditary Angioedema
Angioneurotic Edema
Genetic Disorders
Interventions Drug: recombinant human C1 inhibitor
Drug: Placebo
Enrollment 75
Recruitment Details During the double-blind phase of the study, patients were randomized once to receive 100 IU/kg "rhC1INH" or Saline in a ratio of 1:1. After conclusion of the double-blind phase, patients with subsequent eligible attacks could be treated with open-label 1 vial (2100 IU) of "rhC1INH".
Pre-assignment Details Patients could be enrolled into the open-label phase of the study after conclusion of the double-blind phase.
Arm/Group Title 100 IU/kg "rhC1INH" Saline 1 Vial (2100 IU) "rhC1INH"
Hide Arm/Group Description Includes all subjects randomized and who received 100 IU/kg recombinant human C1 inhibitor in the double-blind phase. Includes all subjects randomized and who received Saline solution in the double-blind phase. Includes all subjects who received, 1 vial (2100 IU) open-label "rhC1INH" in the open-label extension phase. Patients received 1 vial initially and could receive an additional 1-2 vials within 4 hours at the investigator's discretion.
Period Title: Double-blind Phase
Started 16 16 0
Completed 15 15 0
Not Completed 1 1 0
Reason Not Completed
Lost to Follow-up             1             0             0
worsening of "HAE" symptoms             0             1             0
Period Title: Open-label Phase
Started 0 0 57 [1]
Completed 0 0 57
Not Completed 0 0 0
[1]
14/57 patients crossed over from the double-blind phase (7/14 were treated with 100 U/kg "rhC1INH")
Arm/Group Title 100 IU/kg "rhC1INH" Saline 1 Vial (2100 IU) "rhC1INH" Total
Hide Arm/Group Description Includes all subjects randomized who received 100 IU/kg recombinant human C1 inhibitor in the double-blind phase. Includes all subjects randomized and who received Saline solution in the double-blind phase. Includes all subjects who received 1 vial (2100 IU) open-label "rhC1INH" in the open-label extension phase. Total of all reporting groups
Overall Number of Baseline Participants 16 16 43 75
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 16 participants 43 participants 75 participants
<=18 years
1
   6.3%
1
   6.3%
9
  20.9%
11
  14.7%
Between 18 and 65 years
13
  81.3%
12
  75.0%
33
  76.7%
58
  77.3%
>=65 years
2
  12.5%
3
  18.8%
1
   2.3%
6
   8.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 16 participants 43 participants 75 participants
Female
8
  50.0%
9
  56.3%
28
  65.1%
45
  60.0%
Male
8
  50.0%
7
  43.8%
15
  34.9%
30
  40.0%
1.Primary Outcome
Title Time to Beginning of Relief of Symptoms
Hide Description The time to beginning of relief of symptoms has been assessed by using a patient-reported visual analogue scale ("VAS") ranging from 0 mm (no symptoms at all) to 100 mm (extremely disabling). Time to beginning of relief of symptoms at the location that showed first "VAS" score decrease of at least 20 mm from baseline score (t= 0 min) to the next assessment time-point). Assessment time-points were taken on pre-scheduled time-points after drug administration: baseline (0 minutes), 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 48 hours. Time to beginning of relief has been calculated as median time, by using the exact time-points on which each assessment was performed.
Time Frame up to 48 hours after study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set ("FAS" or "mITT") was defined as the set of patients who provided Informed Consent, were randomized and took at least one dose of the study drug administration.
Arm/Group Title 100 IU/kg "rhC1INH" Saline 1 Vial (2100 IU) "rhC1INH"
Hide Arm/Group Description:
Includes all subjects randomized who received 100 IU/kg recombinant human C1 inhibitor in the double-blind phase.
Includes all subjects randomized and who received Saline solution in the double-blind phase.
Includes all subjects who received 1 vial (2100 IU) open-label "rhC1INH" in the open-label extension phase.
Overall Number of Participants Analyzed 16 16 57
Median (Full Range)
Unit of Measure: minutes
62
(15 to 1470)
508
(15 to 2880)
61
(15 to 1455)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 100 IU/kg "rhC1INH", Saline
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
2.Secondary Outcome
Title Time to Minimal Symptoms
Hide Description the time to minimal symptoms was the time to minimal symptoms for an attack, assessed using the Visual Analogue Scale ("VAS") score. Symptoms were said to be minimal when the "VAS" score at all locations was below 20 mm. Assessment time-points were: baseline (0 minutes), 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 48 hours. Time to minimal symptoms has been calculated by using the exact time-points on which each assessment was performed.
Time Frame up to 48 hours after study drug administration
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set ("FAS" or "mITT") was defined as the set of patients who provided Informed Consent, were randomized and took at least one dose of study drug administration.
Arm/Group Title 100 IU/kg "rhC1INH" Saline 1 Vial (2100 IU) "rhC1INH"
Hide Arm/Group Description:
Includes all subjects randomized who received 100 IU/kg recombinant human C1 inhibitor in the double-blind phase.
Includes all subjects randomized and who received Saline solution in the double-blind phase.
Includes all subjects who received 1 vial (2100 IU) open-label "rhC1INH" in the open-label extension phase.
Overall Number of Participants Analyzed 16 16 57
Median (Full Range)
Unit of Measure: minutes
480
(15 to 2400)
1440
(31 to 2885)
241
(15 to 4333)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 100 IU/kg "rhC1INH", Saline
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Time Frame Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 100 IU/kg "rhC1INH" Saline 1 Vial (2100 IU) "rhC1INH"
Hide Arm/Group Description Includes all subjects randomized who received 100 IU/kg recombinant human C1 inhibitor in the double-blind phase. Includes all subjects randomized and who received Saline solution in the double-blind phase. Includes all subjects who received 1 vial (2100 IU) open-label "rhC1INH" in the open-label extension phase.
All-Cause Mortality
100 IU/kg "rhC1INH" Saline 1 Vial (2100 IU) "rhC1INH"
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
100 IU/kg "rhC1INH" Saline 1 Vial (2100 IU) "rhC1INH"
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/16 (0.00%)      2/16 (12.50%)      0/57 (0.00%)    
Hepatobiliary disorders       
Biliary colic  1  0/16 (0.00%)  0 1/16 (6.25%)  1 0/57 (0.00%)  0
Investigations       
Prostate examination  1  0/16 (0.00%)  0 1/16 (6.25%)  1 0/57 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (9.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
100 IU/kg "rhC1INH" Saline 1 Vial (2100 IU) "rhC1INH"
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/16 (12.50%)      5/16 (31.25%)      6/57 (10.53%)    
Gastrointestinal disorders       
nausea  1  0/16 (0.00%)  0 0/16 (0.00%)  0 3/57 (5.26%)  3
General disorders       
pain  1  0/16 (0.00%)  0 2/16 (12.50%)  2 0/57 (0.00%)  0
Musculoskeletal and connective tissue disorders       
pain in extremity  1  0/16 (0.00%)  0 1/16 (6.25%)  1 0/57 (0.00%)  0
Nervous system disorders       
headache  1  1/16 (6.25%)  1 2/16 (12.50%)  2 3/57 (5.26%)  3
Reproductive system and breast disorders       
menstrual disorder  1  1/16 (6.25%)  1 0/16 (0.00%)  0 0/57 (0.00%)  0
scrotal swelling  1  1/16 (6.25%)  1 0/16 (0.00%)  0 0/57 (0.00%)  0
Vascular disorders       
hypotension  1  0/16 (0.00%)  0 1/16 (6.25%)  1 0/57 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (9.1)
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.
The investigator must provide a copy of any results communication to the sponsor for review at least 30 days prior to its submission or disclosure. The sponsor may request to delete information identified by sponsor as confidential information prior to submitting such manuscript and/or abstract for publication. For a multi-center study, the investigator must wait (i) at least 24 months after the study is completed at all sites or (ii) until after the multi-center publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Affairs Department
Organization: Pharming Technologies BV
Phone: +31715247400
EMail: medicalinfo@pharming.com
Layout table for additonal information
Responsible Party: Pharming Technologies B.V.
ClinicalTrials.gov Identifier: NCT00262301    
Other Study ID Numbers: C1 1304-01
First Submitted: December 1, 2005
First Posted: December 6, 2005
Results First Submitted: July 27, 2012
Results First Posted: August 30, 2012
Last Update Posted: October 2, 2012