A Phase 2 HAE Prophylaxis Study With Recombinant Human C1 Inhibitor

A Phase 2 Multicenter, Randomized, Double-Blind, Placebo-Controlled, 3-Period Crossover Study to Evaluate the Efficacy and Safety of Recombinant Human C1 Inhibitor in the Prophylaxis of Angioedema Attacks in Patients With Hereditary Angioedema (HAE)

Primary Objective:

To evaluate the efficacy of recombinant human C1 inhibitor (rhC1INH) in the prophylaxis of angioedema attacks in patients with HAE

Secondary Objective:

To evaluate the safety and immunogenicity of recombinant human C1 inhibitor (rhC1INH) in the prophylaxis of angioedema attacks in patients with HAE

Study Overview

• Status: Completed
• Conditions: Hereditary Angioedema
• Intervention / Treatment: Other: Placebo; Biological: Recombinant human C1 inhibitor

Detailed Description

Study Design:

This is a multi-center, randomized, double-blind, placebo-controlled, 3-period crossover study of rhC1INH in prophylaxis of angioedema attacks in patients with HAE.

Medical screening (clinical and laboratory parameters) will be performed and patient medical history specific to HAE attacks will be collected to assess eligibility. Each patient will receive three 4 week periods of treatment twice weekly.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1G6C6
      • Ottawa Allergy Research Corp
• Czechia
  • Brno, Czechia, 65691
    • Faculty Hospital by St. Anna Brno, Department of clinical Immunology and Allergology
• Italy
  • Milan, Italy, 20157
    • Azienda Ospedaliera Universitaria Luigi Sacco Di Milano
• Macedonia, The Former Yugoslav Republic of
  • Skopje, Macedonia, The Former Yugoslav Republic of, 1000
    • PHI University Clinic of Dermatology
• Romania
  • Mures
    • Sângeorgiu de Mureş, Mures, Romania, 547530
      • SC Centrul Clinic Mediquest SRL
• Serbia
  • Belgrade, Serbia
    • Clinical Center Serbia
• United States
  • Florida
    • Tampa, Florida, United States, 33613
      • University of South Florida Asthma, Allergy and Immunology Clinical Research Unit
    • Tampa, Florida, United States, 33613
      • University of South Florida, Asthma, Allergy & Immunology Clinical Research Unit
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Washington University Division of Allergy and Immunology
  • Oregon
    • Lake Oswego, Oregon, United States, 97035
      • Baker Allergy, Asthma and Dermatology Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patients fulfilling the following criteria at Screening are eligible for participation in the study:

1. Age 13 years or older
2. Laboratory confirmed diagnosis of HAE
3. A history of frequent HAE attacks (at least 4 attacks per month across a minimum of 3 consecutive months).
4. Female patients of childbearing potential who are sexually active must be willing to use an acceptable form of contraception.
5. Provided written informed consent (and written assent for minors)
6. Willingness and ability to comply with all protocol procedures

Exclusion Criteria:

Patients who meet any of the following criteria at Screening are to be excluded from study participation:

1. Patients with medical history of allergy to rabbits or rabbit-derived products (including rhC1INH)
2. Diagnosis of acquired angioedema (AAE)
3. Patients who are pregnant, or breastfeeding, or are currently intending to become pregnant
4. Treatment with any investigational drug in the past 30 days
5. Patients with any condition or treatment that, in the opinion of the Investigator, might interfere with the evaluation of study objectives
6. Patients currently treated with angiotensin-converting enzyme (ACE) inhibitors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rhC1INH twice weekly; rhC1INH administered twice weekly	Biological: Recombinant human C1 inhibitor; Other Names: rhC1INH; Ruconest; Conestat alfa
Experimental: rhC1INH once weekly; rhC1INH administered once weekly	Biological: Recombinant human C1 inhibitor; Other Names: rhC1INH; Ruconest; Conestat alfa
Placebo Comparator: Placebo (Saline) twice weekly; Placebo (Saline) administered twice weekly	Other: Placebo; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of HAE Attacks	Average number of HAE attacks normalized to a 28 day period	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	Number of participants that experienced Treatment Emergent Adverse Events observed in safety population	20 weeks
Percentage of Participants Achieving at Least 50% Reduction in Number of Attacks	Percentage of participants achieving at least 50% reduction in the number of attacks normalized to a 28-day period as compared to the placebo treatment period	28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity	Number of participants analyzed for neutralizing C1INH-specific antibodies and neutralizing rhC1INH-specific antibodies after confirmed anti-C1INH and anti rhC1INH IgM or IgG antibodies	20 weeks

Collaborators and Investigators

• Sponsor: Pharming Technologies B.V.

Publications and helpful links

General Publications

• Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2.
• Riedl MA, Grivcheva-Panovska V, Moldovan D, Baker J, Yang WH, Giannetti BM, Reshef A, Andrejevic S, Lockey RF, Hakl R, Kivity S, Harper JR, Relan A, Cicardi M. Recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema: a phase 2, multicentre, randomised, double-blind, placebo-controlled crossover trial. Lancet. 2017 Sep 30;390(10102):1595-1602. doi: 10.1016/S0140-6736(17)31963-3. Epub 2017 Jul 25.

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: September 16, 2014
• First Submitted That Met QC Criteria: September 19, 2014
• First Posted (Estimate): September 25, 2014

Study Record Updates

• Last Update Posted (Actual): December 8, 2017
• Last Update Submitted That Met QC Criteria: November 7, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Prophylaxis; HAE; Hereditary Angioedema
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Complement C1 Inhibitor Protein
• Other Study ID Numbers: C1 3201

Drug and device information, study documents

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