Tags

Type your tag names separated by a space and hit enter

An open-label study to evaluate the long-term safety and efficacy of lanadelumab for prevention of attacks in hereditary angioedema: design of the HELP study extension.
Clin Transl Allergy 2017; 7:36CT

Abstract

BACKGROUND

Hereditary angioedema (HAE) is characterized by recurrent attacks of subcutaneous or submucosal edema. Attacks are unpredictable, debilitating, and have a significant impact on quality of life. Patients may be prescribed prophylactic therapy to prevent angioedema attacks. Current prophylactic treatments may be difficult to administer (i.e., intravenously), require frequent administrations or are not well tolerated, and breakthrough attacks may still occur frequently. Lanadelumab is a subcutaneously-administered monoclonal antibody inhibitor of plasma kallikrein in clinical development for prophylaxis of hereditary angioedema attacks. A Phase 1b study supported its efficacy in preventing attacks. A Phase 3, randomized, double-blind, placebo-controlled, parallel-arm study has been completed and an open-label extension is currently ongoing.

METHODS/DESIGN

The primary objective of the open-label extension is to evaluate the long-term safety of repeated subcutaneous administrations of lanadelumab in patients with type I/II HAE. Secondary objectives include evaluation of efficacy and time to first angioedema attack to determine outer bounds of the dosing interval. The study will also evaluate immunogenicity, pharmacokinetics/pharmacodynamics, quality of life, characteristics of breakthrough attacks, ease of self-administration, and safety/efficacy in patients who switch to lanadelumab from another prophylactic therapy. The open-label extension will enroll patients who completed the double-blind study ("rollover patients") and those who did not participate in the double-blind study ("non-rollover patients"), which includes patients who may or may not be currently using another prophylactic therapy. Rollover patients will receive a single 300 mg dose of lanadelumab on Day 0 and the second dose after the patient's first confirmed angioedema attack. Thereafter, lanadelumab will be administered every 2 weeks. Non-rollover patients will receive 300 mg lanadelumab every 2 weeks regardless of the first attack. All patients will receive their last dose on Day 350 (maximum of 26 doses), and will then undergo a 4-week follow-up.

DISCUSSION

Prevention of attacks can reduce the burden of illness associated with HAE. Prophylactic therapy requires extended, repeated dosing and the results of this study will provide important data on the long-term safety and efficacy of lanadelumab, a monoclonal antibody inhibitor of plasma kallikrein for subcutaneous administration for the treatment of HAE. Trial registration NCT02741596.

Authors+Show Affiliations

University of California - San Diego School of Medicine, 8899 University Center Lane, Suite 230, San Diego, CA 92122 USA.Department of Internal Medicine/Allergy Section Cincinnati, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML#563, Cincinnati, OH 45267 USA.Department of Medicine and Pediatrics, Penn State University, Allergy, Asthma and Immunology, 500 University Drive, Hershey, PA 17033 USA.Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Cox 201, Boston, MA 02114 USA.Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.Department of Biomedical and Clinical Sciences, Luigi Sacco, University of Milan, ASST Fatebenefratelli-Sacco Milan, Via G.B. Grassi 74, 20157 Milan, Italy.Department of Immunology, Barts Health NHS Trust, 80 Newark Street, London, E1 2ES UK.Triumpharma Inc., 07 Building, Al Yarooty Street, PO Box 2233, Amman, 11941 Jordan.Ottawa Allergy Research Corporation, University of Ottawa Medical School, 110-2935 Conroy Road, Ottawa, ON K1G 6C6 Canada.Shire, 300 Shire Way, Lexington, MA 02421 USA.Shire, 300 Shire Way, Lexington, MA 02421 USA.Division of Clinical Immunology and Allergy, Department of Medicine, Icahn School of Medicine at Mount Sinai, 5 East 98th Street 11th Floor, New York, NY 10029 USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29043014

Citation

Riedl, Marc A., et al. "An Open-label Study to Evaluate the Long-term Safety and Efficacy of Lanadelumab for Prevention of Attacks in Hereditary Angioedema: Design of the HELP Study Extension." Clinical and Translational Allergy, vol. 7, 2017, p. 36.
Riedl MA, Bernstein JA, Craig T, et al. An open-label study to evaluate the long-term safety and efficacy of lanadelumab for prevention of attacks in hereditary angioedema: design of the HELP study extension. Clin Transl Allergy. 2017;7:36.
Riedl, M. A., Bernstein, J. A., Craig, T., Banerji, A., Magerl, M., Cicardi, M., ... Busse, P. J. (2017). An open-label study to evaluate the long-term safety and efficacy of lanadelumab for prevention of attacks in hereditary angioedema: design of the HELP study extension. Clinical and Translational Allergy, 7, p. 36. doi:10.1186/s13601-017-0172-9.
Riedl MA, et al. An Open-label Study to Evaluate the Long-term Safety and Efficacy of Lanadelumab for Prevention of Attacks in Hereditary Angioedema: Design of the HELP Study Extension. Clin Transl Allergy. 2017;7:36. PubMed PMID: 29043014.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An open-label study to evaluate the long-term safety and efficacy of lanadelumab for prevention of attacks in hereditary angioedema: design of the HELP study extension. AU - Riedl,Marc A, AU - Bernstein,Jonathan A, AU - Craig,Timothy, AU - Banerji,Aleena, AU - Magerl,Markus, AU - Cicardi,Marco, AU - Longhurst,Hilary J, AU - Shennak,Mustafa M, AU - Yang,William H, AU - Schranz,Jennifer, AU - Baptista,Jovanna, AU - Busse,Paula J, Y1 - 2017/10/06/ PY - 2017/03/22/received PY - 2017/09/19/accepted PY - 2017/10/19/entrez PY - 2017/10/19/pubmed PY - 2017/10/19/medline KW - Bradykinin KW - C1-inhibitor KW - Hereditary angioedema KW - Lanadelumab KW - Monoclonal antibody KW - Orphan disease KW - Plasma kallikrein KW - Prophylaxis KW - Rare disease SP - 36 EP - 36 JF - Clinical and translational allergy JO - Clin Transl Allergy VL - 7 N2 - BACKGROUND: Hereditary angioedema (HAE) is characterized by recurrent attacks of subcutaneous or submucosal edema. Attacks are unpredictable, debilitating, and have a significant impact on quality of life. Patients may be prescribed prophylactic therapy to prevent angioedema attacks. Current prophylactic treatments may be difficult to administer (i.e., intravenously), require frequent administrations or are not well tolerated, and breakthrough attacks may still occur frequently. Lanadelumab is a subcutaneously-administered monoclonal antibody inhibitor of plasma kallikrein in clinical development for prophylaxis of hereditary angioedema attacks. A Phase 1b study supported its efficacy in preventing attacks. A Phase 3, randomized, double-blind, placebo-controlled, parallel-arm study has been completed and an open-label extension is currently ongoing. METHODS/DESIGN: The primary objective of the open-label extension is to evaluate the long-term safety of repeated subcutaneous administrations of lanadelumab in patients with type I/II HAE. Secondary objectives include evaluation of efficacy and time to first angioedema attack to determine outer bounds of the dosing interval. The study will also evaluate immunogenicity, pharmacokinetics/pharmacodynamics, quality of life, characteristics of breakthrough attacks, ease of self-administration, and safety/efficacy in patients who switch to lanadelumab from another prophylactic therapy. The open-label extension will enroll patients who completed the double-blind study ("rollover patients") and those who did not participate in the double-blind study ("non-rollover patients"), which includes patients who may or may not be currently using another prophylactic therapy. Rollover patients will receive a single 300 mg dose of lanadelumab on Day 0 and the second dose after the patient's first confirmed angioedema attack. Thereafter, lanadelumab will be administered every 2 weeks. Non-rollover patients will receive 300 mg lanadelumab every 2 weeks regardless of the first attack. All patients will receive their last dose on Day 350 (maximum of 26 doses), and will then undergo a 4-week follow-up. DISCUSSION: Prevention of attacks can reduce the burden of illness associated with HAE. Prophylactic therapy requires extended, repeated dosing and the results of this study will provide important data on the long-term safety and efficacy of lanadelumab, a monoclonal antibody inhibitor of plasma kallikrein for subcutaneous administration for the treatment of HAE. Trial registration NCT02741596. SN - 2045-7022 UR - https://www.unboundmedicine.com/medline/citation/29043014/An_open_label_study_to_evaluate_the_long_term_safety_and_efficacy_of_lanadelumab_for_prevention_of_attacks_in_hereditary_angioedema:_design_of_the_HELP_study_extension_ L2 - https://ctajournal.biomedcentral.com/articles/10.1186/s13601-017-0172-9 DB - PRIME DP - Unbound Medicine ER -