Proof-HD' trial with Pridopidine in Huntington's disease

The first European patients in the Phase 3 'Proof-HD' trial with Pridopidine in Huntington's disease are from Italy and Germany


The first two Italian patients started the trial today, January 20, 2021, in Rome, at the CSS-Mendel Institute, section of IRCCS Casa Sollievo della Sofferenza and Coordinating Center for Italy, under the guidance of Principal Investigator Prof. Ferdinando Squitieri.

PROOF-HD (PRidopidineOutcome On Function in Huntington Disease) is a Phase 3, randomized, double-blind versus placebo, multinational, multicenter trial to evaluate the efficacy and safety of Pridopidine in patients in the early stage of Huntington's disease

The trial aims to test the efficacy of the molecule on the course of the disease by investigating the functional capacity of patients. The main expected result (primary endpoint) is, in fact, a significant improvement in autonomy, measured through the assessment scale TFC (Total Functional Capacity). The impairment of functional capacity, i.e. the inability to conduct normal daily activities, is what regulatory authorities believe has the most significant impact on patients' lives.

Over the years, patients and their families have constantly stressed the disease's impact on the impairment of daily activities: such as, for instance, not being able to work, drive, carry out simple household activities, feed themselves, take care of themselves (washing, dressing) and practice their hobbies and sports. Patients themselves highlighted what it had been taken from them in becoming increasingly dependent on others as the symptoms of the disease worsened (Source: Food and Drug Administration's 'Voice of Patient', September 22, 2015). 

Therefore, if this molecule is indeed able to affect autonomy, this would mean an improvement in the quality of life for people with Huntington's disease.

Preliminary data encourage the belief that pridopidine may represent the first drug capable of acting on these specific patient frailties, although, to date, definitive confirmation of its efficacy has not yet been found.

"Previously the aim was to investigate a symptomatic effect of the molecule on the motor aspect, now instead it will be explored the effect on the autonomy of people. Today, moreover, unlike the past, we know much more about the relationship between the drug dosage and mechanism, so this is the right time to conduct this trial, designed to verify the impact on autonomy" - says Prof. Ferdinando Squitieri, who explains the action of Pridopidine stating that "the drug interacts with the Sigma-1 receptor, thus playing a biological and potentially neuroprotective role"

Therefore, no longer a symptomatic effect, but a potential neuroprotective effect able to slow down the course of the disease.

The study is conducted in the United States, Canada and Europe and involves 480 patients. 

Ralf Reilmann, MD, PhD, FAAN, Founding Director of the George-Huntington-Institute in Münster (Germany) and European Global Principal Investigator of the study, said: “Pridopidine has shown promising efficacy signs on everyday function and motor symptoms in earlier studies, making me confident of the potential of this orally available drug to have a positive effect for HD patients. Similarly to Prof. Squitieri’s clinic, my team has already had the opportunity to care for more than 50 patients treated with Pridopidine in previous studies where we observed a positive safety profile. We are excited that PROOF-HD now allows us to jointly explore a new therapeutic option for HD patients by assessing the efficacy of Pridopidine in early-HD patients in a properly powered global Phase 3 study. I would like to thank Prof. Squitieri and his committed team and all study participants and their families in Italy for their support for this international collaborative study.”

In Italy, the sites involved are the Mendel Institute of Genetics/Fondazione IRCCS Casa Sollievo della Sofferenza (Coordinating Center), the IRCCS Carlo Besta of Milan, the University Hospital "Federico II" of Naples, the Policlinico di Bari "Ospedale Giovanni XXIII", the IRCSS - Institute of Neurological Sciences of Bologna. It is expected the involvement of 40 patients.

To learn more:

Proof-HD trial 

Presentation of Proof-HD study by Prof. Hayden:

Prilenia website: