What is a clinical trial?
A clinical trial is performed to assess the efficacy and safety of new treatments that will eventually receive a market authorization. Clinical trials are preceded by preclinical research (in animal or cell models) to confirm their relevance and safety.
What are the different phases of clinical trials?
Consists of the study of the molecule, its structure, its effect on cells, its effect on animals at the behavioral and biological level, and the study of target organs. It is carried out in vitro then in vivo on animal models, generally rodents (mice and rats).
Assesses tolerance and absence of adverse effects in mostly healthy volunteers. The groups studied are usually small (less than 100 participants). Absence of significant side effects conditions the pursue of a given therapeutic strategy.
Phase II, also called “the pilot study”, consists of determining the optimal dose of the drug and its possible side effects. This is usually performed double blind and randomized, comparing the agent and placebo. The groups studied are of medium size (usually around 100). Two groups of patients are formed by drawing lots (randomization), so as to constitute homogeneous and comparable groups (age, sex, characteristics of the disease, etc.): one will receive the reference treatment or placebo and the other the new treatment. The term “double blind” is used when neither the patient nor the caregiver knows what treatment is being given.
Phase III, or “pivotal study”, is the final comparative efficacy study performed on large multiple clinical centers and several hundreds of patients to assess the efficacy of a treatment versus placebo. This trial is evaluated by European and/or US authorities to enable market authorization if the results are satisfactory.
Phase IV, or “post-marketing”, is the long-term follow-up of a treatment while the treatment is authorized on the market. This phase allows to detect possible rare side effects or late complications. This phase is under the responsibility of the pharmaceutical laboratories and thanks to its close monitoring is called “pharmacovigilance”.
Neurochlore’s clinical trials
Clinical trials with positive results on the use of Bumetanide to treat Autism have been performed on more than 120 children with Autism Spectrum Disorders (ASD). After two successful phase II clinical trials (Lemonnier et al., 2012 and 2017). Then, several independant studies validated the effectiveness of this molecule on ASD. This permits to start a phase III approved by the European authorities. Neurochlore signed a licensing partnership with Servier Laboratories granting it development and marketing rights in Europe.
The purpose of phase III was to validate the efficacy of Bumetanide and to submit a marketing application in Europe. The trial, divided into 2 subgroups (2 to 7 years old and <7 to 18 years old), included 420 children recruited from 40 centers in Europe/Brazil/Australia and USA. They were divided into “on treatment (0.5mg)” and “on placebo” for 6 months. Unfortunately, the results were negative, with no significant differences between treated and placebo in the primary endpoint and secondary endpoints, for both groups.
The details of the studies are available on the following sites:
- For the study of children aged from 2 to less than 7 years old: https://clinicaltrials.gov/ct2/show/NCT03715153
- For the study of children aged from 7 to less than 18 years old: https://clinicaltrials.gov/ct2/show/NCT03715166
Bumetanide was administered in liquid form, approved and tested in phases 2 and 3.
The vials are dosed for 1 month (1mg morning and evening).
La phase II B qui vérifie l’efficacité et détermine la dose optimale a réussi, mais la phase III n’a malheureusement pas montré de réelle différence entre la Bumétanide et un placébo.
The phase II.B which verifies the effectiveness and determines the optimal dose was successful, but the phase III unfortunately did not show any real difference between Bumetanide and a placebo.
This result preventing us from finding future investors, Neurochlore will therefore stop its clinical trials.