Date: 2016-05-03
Type of information: Results
phase: 1-2a
Announcement: results
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 (RSV) infection
Therapeutic area: Infectious diseases - Respiratory diseases
Country: Australia, Belgium, Bulgaria, Estonia, Hungary, Israel, Latvia, Malaysia, Philippines, Poland, Slovakia, Spain, Thailand, UK
Trial
details: The primary objective of the study is to investigate the safety and tolerability of ALX-0171. The secondary objectives are to evaluate the clinical effect of ALX-0171 and to explore the pharmacodynamics (PD) and the systemic pharmacokinetics (PK) of ALX-0171.The study consists of two parts. The first part is an open-label “lead-in” part to assess the safety of ALX-0171 in five patients who will receive a once-daily inhaled dose of ALX-0171 for three consecutive days. Following a positive recommendation after review of these “lead-in” safety data by an independent data monitoring committee (DMC), 30 patients will be enrolled in the subsequent double-blind, placebo controlled part of the study in which patients will be randomly assigned to receive either, a once-daily inhaled dose of ALX-0171 or placebo, for three consecutive days. (NCT02309320) At the end of September 2014, the European Medicines Agency (EMA) approved the Paediatric Investigation Plan (PIP) for ALX-0171. In December 2014, Ablynx opened recruitment for the first-in-infant Phase I/IIa safety study with inhaled ALX-0171 in otherwise healthy infants (aged 3-24 months) diagnosed with RSV and hospitalised for lower respiratory tract infection. The study has recruited 35 hospitalised infants in multiple clinical centres in Europe and the Asia-Pacific region. The primary endpoint of the study is safety and tolerability of ALX-0171. Secondary endpoints include clinical effect (including effect on feeding, respiratory rate, wheezing, coughing, general appearance and clinical scores), immunogenicity, pharmacokinetics (PK) and pharmacodynamics (PD) of inhaled ALX-0171.
Latest
news: * On May 3, 2016, Ablynx announced top line results from the first-in-infant Phase I/IIa study of its wholly-owned, inhaled, anti-RSV Nanobody, ALX-0171, in 53 infants, aged 1-24 months, hospitalised as a result of a respiratory syncytial virus (RSV) infection. The study met its primary endpoint, demonstrating the favourable safety and tolerability profile of ALX-0171 when administered daily by inhalation in the target infant population, with no treatment-related serious adverse events reported. ALX-0171 was detected in the serum of subjects after treatment, consistent with lung exposure. Anti-drug antibodies had no effect on the pharmacokinetics and no relation with adverse events was seen. Treatment with inhaled ALX-0171 had an immediate impact on viral replication and also reduced viral load, as compared to placebo. Analysis of a composite of clinical efficacy endpoints, the Global Severity Score, led to an encouraging initial indication of a therapeutic effect for infants treated with ALX-0171. Ablynx believes that these results strongly support advancement into a Phase II efficacy study. * On December 17, 2015, Ablynx announced that it has completed target enrolment of the first-in-infant Phase I/IIa safety study with its anti-RSV Nanobody, ALX-0171, and is on track to publish top line results in the first half of 2016. ALX-0171 is a wholly-owned Nanobody drug candidate, administered through inhalation, for the treatment of respiratory syncytial virus (RSV) infection in infants. Ablynx also announced that following a positive recommendation from an independent Data Monitoring Committee (DMC) based on data available for the first 15 infants from the placebo-controlled part of this Phase I/IIa safety study, the age requirement for infants in the trial has been reduced from 3 months to 1 month. The Phase I/IIa study will now continue with an expansion cohort enrolling younger infants aged 1-5 months during the remaining RSV season in Northern Europe. This will enable the collection of additional data on ALX-0171 in a younger patient population. Results from this extension will be available in the second half of 2016. The company is also preparing the initiation of the next clinical study in infants, which is expected to start recruiting by the end of 2016.
* On December 17, 2014, Ablynx announced that it has opened recruitment in the initial clinical centres for the first-in-infant Phase IIa study with ALX-0171, administered through inhalation. The Phase IIa study is a multi-centre, multi-country trial to evaluate the safety, tolerability and clinical activity (including effect on feeding, respiratory rate, wheezing, coughing and general appearance) of ALX-0171, administered via inhalation, in otherwise healthy infants and toddlers (aged 5-24 months) diagnosed with RSV and hospitalised for a lower respiratory tract infection. The study will be run in five European countries with potential additional sites available in the Southern Hemisphere as risk mitigation for the unpredictable length and severity of the European RSV season. The study is expected to be completed in Q2 2015 with results anticipated in Q3 2015.
