Clinical trials for Molgradex
Molgradex (recombinant human GM-CSF) is being developed for the treatment of pulmonary alveolar proteinosis (PAP) – a rare lung disease with no current medical treatment. Standard treatment is whole lung lavage (WLL).
Read more about WLL
Pivotal phase II/III clinical trial, IMPALA
Savara is currently conducting a pivotal clinical phase II/III trial in Europe including Russia and Israel. The trial has been named IMPALA and its primary aim is to confirm the efficacy and safety of Molgradex® in PAP patients. IMPALA is a randomized, double-blind, placebo-controlled multicenter trial lead by Coordinating Principal Investigator Dr. Cliff Morgan from the Royal Brompton Hospital in London, United Kingdom.
The patients will be dosed with Molgradex or placebo. Up to 51 patients to be recruited to the trial during a period of estimated one year. Top line data from the treatment period is expected 1H 2018. The first patient was dosed May 2016.
Why phase II/III?
IMPALA is a phase II trial in that Molgradex is tested in patients for the first time. It is, however, also pivotal in that the results of this trial will form the basis of a future marketing authorization in Europe and Japan. Effectively, phase II and III have been combined in the IMPALA trial .
Read more about the IMPALA trial
Phase I trial in healthy volunteers
Savara has finalized and received data from phase I clinical trial – a randomized, double-blind, placebo-controlled, single-center, single-ascending dose (SAD) and multiple ascending-dose (MAD) study. Its objectives were to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of molgramostim when administered by inhalation to healthy adult subjects.
The trial enrolled 42 healthy adults and was conducted by Celerion in Belfast, Northern Ireland. Initial data from the trial were published October 2015.
- Drug formulation was well tolerated at all dose levels; no serious or severe treatment emergent adverse events were registered.
- None of the subjects developed antibodies against Molgradex.
- Number of Molgradex treated subjects reporting treatment emergent adverse events was similar to that seen in placebo.
- The number of related treatment emergent adverse events per subject was higher in Molgradex treated subjects (2.1 per subject in the active group >< 1.4 per subject in the placebo group).
- Mild cough was the most frequently related adverse event. The number of subjects reporting any treatment emergent adverse events was similar to that seen in placebo.
- The number of treatment related cough events per subject was higher in Molgradex treated subjects (1.6 per subject in the active group >< 1.25 in the placebo group).
- In line with the expected efficacy of GM-CSF 28/30 subjects in the Molgradex groups reported a mild increase of white blood cell counts characterized as ‘not clinically significant’.
- In two subjects the increase of white blood cell counts were reported as ’mild adverse events’.
- The concentration of Molgradex measured in the blood after inhalation was 50-100 times lower than after systemic administration of GM-CSF.
The results of the phase I clinical trial were presented at ATS (American Thoracic Society) congress in May 2016. Scientific poster attached.
Read more about the phase I clinical trial here.