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Efficacy, Safety and Immunogenicity Study of Recombinant Human C1 Inhibitor for the Treatment of Acute HAE Attacks

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01188564
Recruitment Status : Completed
First Posted : August 25, 2010
Results First Posted : August 7, 2015
Last Update Posted : August 7, 2015
Sponsor:
Information provided by (Responsible Party):
Pharming Technologies B.V.

Tracking Information
First Submitted Date  ICMJE August 24, 2010
First Posted Date  ICMJE August 25, 2010
Results First Submitted Date  ICMJE June 10, 2015
Results First Posted Date  ICMJE August 7, 2015
Last Update Posted Date August 7, 2015
Study Start Date  ICMJE January 2011
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 3, 2015)
Time to Beginning of Relief of Symptoms [ Time Frame: Patients observed for 24 hours ]
Time to beginning of relief is the time lapsed from the beginning of the infusion of study medication to the beginning of a beneficial effect based on patient's responses to the Treatmetn Effect Questionnaire (TEQ) for the primary attack location. The beginning of relief is defined as the first timepoint at which
  • The patient reports any of the following answers for TEQ question 1: "A little better", "Better" or "Much better"; and;
  • The patient reports the following answer for TEQ question 2: "Yes"; and,
  • There is persistence in improvement at the next assessment time, i.e.either the same or a better response to Question 1 and "Yes" to Question 2.
Original Primary Outcome Measures  ICMJE
 (submitted: August 24, 2010)
Time to beginning of relief based on the VAS, completed by the patient [ Time Frame: Patients observed for at least 8 hours ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 3, 2015)
Time to Minimal Symptoms [ Time Frame: 24 hours ]
The key secondary efficacy endpoint was the time to minimal symptoms at all locations. The time to achieving minimal symptoms was defined as an answer of "Yes" to TEQ question 3.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 24, 2010)
  • Minimal important difference (MID) of the overall VAS score
  • Time to beginning of relief based on the MID
  • Time to beginning of relief based on the Investigator Score
  • IgM and IgG antibodies against recombinant human C1INH (anti-rhC1INH)
  • Antibodies against host related impurities (anti-HRI)
  • Adverse events
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy, Safety and Immunogenicity Study of Recombinant Human C1 Inhibitor for the Treatment of Acute HAE Attacks
Official Title  ICMJE A Phase III Randomized, Double-blind, Placebo-controlled Study With an Open-label Extension Evaluating the Efficacy, Safety and Immunogenicity of Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks of Angioedema in Patients With HAE
Brief Summary This study is being conducted to confirm the efficacy, safety, and immunogenicity of recombinant human C1 inhibitor (rhC1INH) at a dose of 50 U/kg when used for the treatment of acute angioedema attacks in Hereditary Angioedema (HAE) patients.
Detailed Description

HAE is characterized by recurrent localized angioedema caused by uncontrolled activation of the complement and contact systems due to a congenital deficiency of functional C1 inhibitor.

rhC1INH has been developed to offer a more widely available therapeutic alternative to the existing plasma-derived C1INH (pdC1INH) products that have been used in the treatment of acute angioedema attacks patients with HAE.

Patients who have qualified for enrollment in advance and who present to a study center within 5 hours of onset of an attack will be evaluated for eligibility. 75 eligible patients will be randomized (3:2) to receive an intravenous infusion of rhC1INH or saline in a double-blind fashion. Open-label rhC1INH may be provided as rescue medication to patients who do not experience the beginning of relief within 4 hours or who experience life-threatening oropharyngeal-laryngeal angioedema symptoms.

Any patient having received a randomized treatment will be allowed to receive treatment with rhC1INH in an open-label fashion for subsequent eligible attacks.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Hereditary Angioedema
Intervention  ICMJE
  • Drug: rhC1INH
    One i.v. injection of rhC1INH at the dose of 50 U/kg, for patients up to 84 kg; one i.v. injection of rhC1INH at the dose of 4200U (2 vials) for patients of 84 kg body weight or greater.
  • Drug: Placebo (Saline)
    One i.v. injection of saline (NaCl 0.9% w/v), equivalent in volume to the active treatment
Study Arms  ICMJE
  • Experimental: rhC1INH
    Intervention: Drug: rhC1INH
  • Placebo Comparator: Placebo (Saline)
    Intervention: Drug: Placebo (Saline)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 19, 2011)
75
Original Estimated Enrollment  ICMJE
 (submitted: August 24, 2010)
50
Actual Study Completion Date  ICMJE March 2013
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Aged at least 13 years
  • Signed written informed consent
  • Clear clinical and laboratory diagnosis of HAE with baseline plasma level of functional C1INH of less than 50% of normal
  • Willingness and ability to comply with all protocol procedures
  • Clinical symptoms of an eligible HAE attack with onset less than 5 hours before the time of initial evaluation

Exclusion Criteria:

  • Medical history of allergy to rabbits or rabbit-derived products (including rhC1INH), or positive anti-rabbit dander IgE test (cut off >0.35 kU/L; ImmunoCap® assay; Phadia or equivalent).
  • A diagnosis of acquired C1INH deficiency (AAE)
  • Pregnancy, or breastfeeding, or current intention to become pregnant
  • Treatment with any investigational drug in the past 30 days
  • Known or suspected addiction to drug and/or alcohol abuse
  • Suspicion for an alternate explanation of the symptoms other than acute HAE attack
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 13 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Bulgaria,   Canada,   Hungary,   Israel,   Italy,   Macedonia, The Former Yugoslav Republic of,   Poland,   Romania,   Serbia,   South Africa,   United States
Removed Location Countries Netherlands
 
Administrative Information
NCT Number  ICMJE NCT01188564
Other Study ID Numbers  ICMJE C1 1310
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pharming Technologies B.V.
Study Sponsor  ICMJE Pharming Technologies B.V.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Pharming Technologies B.V.
Verification Date July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP