6 research outputs found
design of the HELP study extension
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
NCT0274159
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
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 Electronic supplementary material The online version of this article (doi:10.1186/s13601-017-0172-9) contains supplementary material, which is available to authorized users