Treatment of Hereditary Angioedema Prodrome with Recombinant C1-esterase Inhibitor (Ruconest)

To assess the efficacy of recombinant human C1-esterase inhibitor in the management of HAE prodrome for preventing the progression from prodrome to an acute angioedema attacks. Subjects will either receive Ruconest after the first 2 prodromes or during the last 2 prodromes. 5 clinic visits will occur within 24 hours of a prodrome. Subjects will complete prodrome severity and angioedema attack diaries

Study Overview

• Status: Completed
• Conditions: Hereditary Angioedema
• Intervention / Treatment: Biological: Ruconest

Detailed Description

After screening, subjects will be followed in the study for four consecutive prodromes. For prodromes designed to be treated with Ruconest, the drug will be administered within 12 hours of prodromal onset and prior to the onset of objective selling. Ruconset will be self-administered at home or by a healthcare professional at the recommended dose of 50 IU/kg body weight with maximum dose of 4200 IU as a slow IV injection over 5 minutes Subjects will be randomized into two arms after enrollment. Subjects in Arm A receives Ruconest after 1st and 2nd prodrome and no Ruconest after 3rd and 4th prodromes. Subjects in Arm B receive no Ruconest after 1st and 2nd prodrome and Ruconest after 3rd and 4th prodromes.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Clinical Research Center of Alabama
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Bernstein Clinical Research Center, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Prior diagnosis of HAE Type 1 and 2,
• One or more HAE attacks per month,
• History of 4 prodromes that proceed to angioedema attacks

Exclusion Criteria:

• History of thrombosis or arterial/venous thromboembolic attacks
• History of atherosclerosis, morbid obesity, immobility
• History of allergy to rabbits or products from rabbits
• History of life-threatening immediate allergic reactions to C1 esterase inhibitor preparations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ruconest; open-label Ruconest	Biological: Ruconest; recombinant human C1-esterase inhibitor
No Intervention: No Ruconest; No Ruconest given

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary endpoint was the difference in response rates in preventing HAE attacks between Conestat Alfa®-treated vs. untreated HAE prodrome events.	A mixed model for repeated measures was used to determine the statistical significance of Conestat Alfa®'s clinical efficacy for treating the HAE prodrome versus the acute attack.	up to 12 months from start of study

Collaborators and Investigators

• Sponsor: Bernstein Clinical Research Center
• Investigators: Principal Investigator: Jonathan Bernstein, MD, Bernstein Clinical Research Center

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2018
• Primary Completion (Actual): April 28, 2022
• Study Completion (Actual): April 28, 2022

Study Registration Dates

• First Submitted: November 12, 2024
• First Submitted That Met QC Criteria: November 13, 2024
• First Posted (Actual): November 15, 2024

Study Record Updates

• Last Update Posted (Actual): November 15, 2024
• Last Update Submitted That Met QC Criteria: November 13, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: prodrome
• Additional Relevant MeSH Terms: Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immunologic Deficiency Syndromes; Skin Diseases; Urticaria; Skin Diseases, Vascular; Angioedema; Angioedemas, Hereditary; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Complement Inactivating Agents; Complement C1 Inhibitor Protein
• Other Study ID Numbers: Ruc01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: not needed for manuscript

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No