Safety, PK, PD of SC ALXN1210 with rHuPH20 in Healthy Volunteers
Research type
Research Study
Full title
A Partially Randomized, Sequential Cohort, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Subcutaneous Ravulizumab Coadministered With rHuPH20 in Healthy Adult Volunteers
IRAS ID
248436
Contact name
Ulrike Lorch
Contact email
Sponsor organisation
Alexion Pharma GmbH
Eudract number
2017-004931-35
Duration of Study in the UK
0 years, 8 months, 1 days
Research summary
We are conducting a clinical study in healthy volunteers with the investigational drug ravulizumab. This is being developed by Alexion Pharmaceuticals, Inc. for the treatment of rare immune system diseases such as paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). These diseases cause the potentially life-threatening breakdown of red blood cells and platelets (hemolysis). Eculizumab (also manufactured by Alexion) is the only approved drug for their treatment. Ravulizumab works in the same way as eculizumab but may be given less frequently and subcutaneously, which may provide a more convenient treatment for patients.\n\nRavulizumab has administered to over 200 healthy volunteers and PNH/aHUS patients intravenously (iv) and subcutaneously (sc) in single and multiple doses in clinical trials. No safety concerns have thus far been identified. In this study, ravulizumab with be co-administered subcutaneously with recombinant human hyaluronidase PH20 (rHuPH20), a ‘spreading agent’ which breaks down hyaluronic acid in subcutaneous tissues, allowing a potentially larger volume (and dose) or ravulizumab to be injected, which may allow less frequent dosing. The aim of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of a single doses of ravulizumab alone (iv and sc) and when co-administered subcutaneously with rHuPH20. \n\nForty-eight volunteers will participate in the study in five cohorts, each lasting up to 270 days, including a screening period of up to 70 days, and a treatment period of 150 days. Cohorts 1 and 5 will receive a single dose of ravulizumab (sc and iv respectively) and cohorts 2 to 4 will receive single ascending doses of ravulizumab and rHuPH20. \n\nWe will assess safety parameters including physical examination, vital signs, laboratory evaluations, electrocardiogram (ECG) and monitoring of adverse events (AEs). Volunteers will be vaccinated against meningitis and will be administered prophylactic antibiotics.\n
REC name
London - London Bridge Research Ethics Committee
REC reference
18/LO/0975
Date of REC Opinion
3 Jul 2018
REC opinion
Favourable Opinion