C1 Esterase Inhibitor Single Dose Crossover Study
Research type
Research Study
Full title
A PHASE 1, RANDOMIZED, SINGLE DOSE, CROSSOVER STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND RELATIVE BIOAVAILABILITY OF SUBCUTANEOUS ADMINISTRATION OF C1 ESTERASE INHIBITOR [HUMAN] LIQUID FOR INJECTION IN HEALTHY VOLUNTEERS FOLLOWING AN INITIAL ASSESSMENT USING THE MARKETED IV FORMULATION
IRAS ID
165652
Contact name
Joseph Chiesa
Contact email
Sponsor organisation
Shire Development LLC and International Affiliates
Eudract number
2014-001605-40
Duration of Study in the UK
0 years, 2 months, 26 days
Research summary
C1 esterase inhibitor [human] is an investigational drug being developed with the aim of helping people with hereditary angioedema (HAE), HAE is a rare genetic disease with a deficiency of C1INH enzyme resulting in the uninhibited production of bradykinin (a molecule involved in inflammation), which promotes inflammation through increased vascular permeability (fluid leakage through blood vessel) and excessive accumulation of fluid in body tissues. Thus, patients with HAE are susceptible to recurrent episodes of debilitating swelling throughout the body. This can affect the face, tongue, larynx, gastrointestinal tract, genitourinary system, and extremities. Laryngeal swelling can occlude the airway and cause death by asphyxiation.
Replacement of C1-INH through IV (intravenous) administration of CINRYZE (comparator product in this study) can prevent the occurrence of angioedema attacks associated with HAE or stop and control the mechanism that causes swelling if an attack does occur.
Some HAE patients have inaccessible peripheral veins for reasons such as obesity (due to steroid treatment) or damaged veins because of frequent infusions. Some patients with HAE may be reluctant to or unable to an IV route. As a result, HAE patients requiring prophylactic therapy may have placement of an indwelling central venous catheter, which can be associated with complications such as infection, bleeding, and thrombosis or stenosis of central veins.
Subcutaneous administration represents an alternative method of administering prophylactic CINRYZE to HAE patients for whom accessing peripheral veins is difficult or when central venous catheters are contraindicated, and may alleviate potential complications associated with IV administration via indwelling catheters.
This is a, single dose, crossover study to evaluate the safety, tolerability, and relative bioavailability (percentage of drug absorbed in to body) of subcutaneous administration of C1 esterase inhibitor liquid for injection in healthy volunteers following an initial assessment using the IV formulation of CINRYZE.
Subjects will receive 1000 U IV dose of CINRYZE (lyophilized formulation) in Treatment Period 1. Subjects will then receive a single dose of 1000 U of C1 esterase inhibitor [human] for injection, and a single dose of 2000U of C1 esterase inhibitor [human] for injection via SC administration in Treatment Period 2 and Treatment Period 3, in randomised order.
REC name
North East - York Research Ethics Committee
REC reference
14/NE/1188
Date of REC Opinion
27 Nov 2014
REC opinion
Further Information Favourable Opinion