Date: 2017-01-11
Type of information: Treatment of the first patient
phase: 2
Announcement: treatment of the first patient
Company: Ablynx (Belgium)
Product: ALX-0171
Action
mechanism: monoclonal antibody/nanobody. ALX-0171 is a trivalent Nanobody product which binds to RSV and neutralizes the virus. This trivalent molecule is the first Nanobody to enter the clinic that will be administered through inhalation instead of injection. It nhibits RSV replication and neutralises RSV activity by blocking virus uptake into cells. The physical robustness of the Nanobody allows administration via inhalation directly to the site of infection, i.e. the respiratory tract including the lungs. ALX-0171 has shown a potent anti-viral effect against recent clinical RSV isolates. The Nanobody was well tolerated in multiple Phase I clinical studies in adults.
Disease: respiratory syncytial virus lower respiratory tract infection
Therapeutic area: Infectious diseases - Respiratory diseases
Country:
Trial
details: The primary objective is to evaluate the anti-viral effect and safety of different doses of inhaled ALX-0171 in subjects hospitalized for Respiratory Syncytial Virus Lower Respiratory Tract Infection (RSV LRTI). The secondary objective is to evaluate the clinical activity, pharmacokinetic (PK) properties, pharmacodynamic (PD) effect and immunogenicity of different doses of inhaled ALX-0171. (NCT02979431)
Latest
news: * On January 11, 2017, Ablynx announced that it has dosed the first patient in the Phase IIb "RESPIRE" dose-ranging efficacy study of ALX-0171, its novel inhaled drug candidate to treat RSV infections. Topline results from this Phase IIb study of inhaled ALX-0171 are expected in the second half of 2018. This Phase IIb study is a randomised, double-blind, placebo-controlled, international, multicentre dose-ranging study of three different doses of inhaled ALX-0171 in approximately 180 infants (aged 1-24 months) diagnosed with RSV and hospitalised for a lower respiratory tract infection. ALX-0171 will be administered once daily for three consecutive days. The study consists of a sequential dose escalation part, which is expected to enrol approximately 36 infants, followed by a parallel part in which approximately 144 infants will be randomly assigned to one of the three dose groups of inhaled ALX-0171, or placebo.
The primary endpoint of the study is to evaluate the anti-viral effect of treatment measured in nasal swabs. Secondary endpoints include safety, pharmacokinetics, clinical activity with assessment of composite clinical scores such as the Global Severity Score (using data on feeding intolerance, medical interventions, respiratory distress, apnoea, general condition and fever), and time to clinical response (i.e. time needed to achieve adequate oxygen saturation and oral feeding ).
Dr Edwin Moses, CEO of Ablynx, commented: "Ablynx is a pioneer in the development of a specific treatment for RSV infections. The start of this efficacy study in hospitalised infants with a RSV infection is another important step forward. If recruitment goes to plan then the study is expected to be completed in the first half of 2018 with results anticipated by the end of 2018."
The primary objective of the recently reported first-in-infant Phase I/IIa study in 53 hospitalised RSV-infected infants, aged 1-24 months, was to evaluate the safety and tolerability of an inhaled dose (1.5 mg/kg) of ALX-0171, administered once daily for three consecutive days. The results from this study demonstrated that ALX-0171 was safe and well tolerated, had a significant and immediate impact on viral replication and that it had an encouraging initial indication of therapeutic effect.
The benign safety profile of inhaled ALX-0171 observed so far supports the study of increased doses of inhaled ALX-0171 in the Phase IIb RESPIRE efficacy trial, to evaluate the maximum potential of this novel drug candidate and to support selection of the optimal dose for future development and commercialisation.
The RESPIRE study will consist of two parts. The first part will be a sequential dose escalation that will include three cohorts of 12 subjects each of whom will be randomly (3:1 ratio) assigned to receive inhaled ALX-0171 or inhaled placebo. The first cohort will evaluate the safety of inhaled ALX-0171 at a dose of 3.0 mg/kg. After the last subject in this cohort has completed treatment, an independent data monitoring committee (DMC) will review the safety data and advise the Company on proceeding to the next cohort with a dose of 6.0 mg/kg, and the same procedure will then be used prior to the third cohort which will be dosed at 9.0 mg/kg. Recruitment will be paused while the DMC reviews each data set. Following completion of the sequential dose escalation part, the remaining 144 subjects will be randomly assigned in a 1:1:1:1 ratio to one of the three dose groups of inhaled ALX-0171 (3.0 mg/kg, 6.0 mg/kg and 9.0 mg/kg) or inhaled placebo. Subjects will receive once daily doses for three consecutive days and the total study duration per subject will be 28 days.
