Pridopidine Phase 3 Study to Evaluate Efficacy and Safety in ALS

Официальное название

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Pridopidine in Participants With Amyotrophic Lateral Sclerosis

Обзор

The goal of this clinical trial is to learn if the drug pridopidine works to treat amyotrophic lateral sclerosis in adults. It will also help to learn about the safety of pridopidine. The main question it aims to answer is: Does pridopidine slow disease progression of ALS? Researchers will compare pridopidine to a placebo (a look-alike substance that contains no drug) to see if pridopidine works to treat ALS. Participants will: Take pridopidine or a placebo by mouth every day for 48 weeks. Afterwards, all participants will take pridopidine for another 48 weeks. Visit the clinic once every 1-3 months for checkups and tests

Подробное описание

This is a Phase 3, randomized study consisting of a double-blind placebo-controlled (DBPC) period followed by an open-label extension (OLE) to evaluate the efficacy and safety of pridopidine administered orally at a dose of 45 mg twice a day in adult participants with early and rapidly progressing ALS. Standard of care treatments (e.g. riluzole, edaravone and Nuedexta) will be allowed as long as participants are on a stable dose for at least 4 weeks prior to dosing. In the DBPC period, participants will be randomized in a 3:2 ratio to the pridopidine and placebo arms.

In the DBPC period, participants will receive pridopidine or placebo for 48 weeks. In the OLE period, all participants will receive pridopidine for 48 weeks, while maintaining the blind to their original randomization for both the participant as well as the Investigator and other clinical staff. The total study duration per participant will be 102 weeks including screening and follow up.

Throughout the study, participants will be assessed through on-site clinic visits and virtual visits (via telephone).

Вмешательства

• Препарат Pridopidine
  Pridopidine hard gelatin capsule.
• Препарат Placebo
  Placebo hard gelatin capsule.

Первичные конечные точки

• Change from baseline through Week 26 and Week 48 in the Revised ALS Functional Rating Scale (ALSFRS-R) total score adjusted for mortality [Срок оценки: Baseline to Week 48]

Вторичные конечные точки (6)

• Overall survival at Week 96 [Срок оценки: Baseline to Week 96]
• Change from baseline through Week 26 and Week 48 in speaking rate as measured by quantitative speech assessment in the clinic [Срок оценки: Baseline to Week 48]
• Change from baseline through Week 48 in intelligibility of speech by quantitative speech assessment in the clinic. [Срок оценки: Baseline to Week 48.]
• Change from baseline through Week 48 in percent predicted slow vital capacity (SVC) [Срок оценки: Baseline to Week 48]
• Change from baseline through Week 48 in the Bulbar subdomain of the ALSFRS-R [Срок оценки: Baseline to Week 48]
• Change from baseline through Week 48 in the Amyotrophic Lateral Sclerosis Assessment Questionnaire - 40 (ALSAQ-40) [Срок оценки: Baseline to Week 48]

Критерии участия

Критерии включения

• Definite ALS or Probable ALS using the El Escorial criteria.
• Symptom onset of ≤18 months at screening.
• Slow vital capacity (SVC) greater or equal to 60% predicted.
• Treatment Research Initiative to Cure ALS (TRICALS) Risk Profile Calculator score, based on the European Network for the Cure of ALS (ENCALS) survival prediction model, in the range of -6 to -2, inclusive, at screening.
• Able to swallow a capsule.

Критерии исключения

• Presence of tracheostomy or permanent assisted ventilation.
• Clinically significant heart disease, clinically significant history of arrhythmia, symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia, or presence of left bundle branch block.
• Presence of unstable psychiatric disease, cognitive impairment, dementia or substance abuse that would impair ability of the participant to provide informed consent and participate in the study.
• Clinically significant and/or unstable medical condition (other than ALS) that may either pose a clinically meaningful risk to the participant and/or to study completion.
• Use of medications that prolong QT interval.
• Previous treatment with pridopidine, gene therapy, or antisense oligonucleotides.
• Confirmed mutation in the SOD1, FUS or C9orf72 gene.
• Pregnancy.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 18 центров

• Barrow Neurological Institute — Phoenix
• California Pacific Medical Center — San Francisco
• University of Colorado CU Anschutz Neurology — Aurora
• Mayo Clinic — Jacksonville
• University of South Florida — Tampa
• Emory University — Atlanta
• Northwestern University — Chicago
• University of Kansas — Fairway
• … и ещё 10 центров

Германия · 6 центров

• ALS outpatient department at Charité - university medicine Berlin — Berlin
• ALS outpatient department at Charité - university medicine Berlin — Berlin
• ALS Clinic Bonn University — Bonn
• University Hospital Jena — Jena
• Universitätsklinikum Schleswig-Holstein — München
• University of Ulm — Ulm

Италия · 6 центров

• University of Campania "Luigi Vanvitelli" — Caserta
• Centro Clinico NEMO Fondazione Serena Onlus - ASST Niguarda Hospital — Milan
• Istituto Auxologico Italiano Ospedale San Luca — Milan
• Azienda Ospedaliero Universitaria Di Modena — Modena
• University of Padova — Padova
• University of Torino — Torino

Франция · 5 центров

• CHU Lille — Lille
• Hôpitaux Universitaires de Marseille Timone — Marseille
• Centre Hospitalier Universitaire de Nice — Nice
• Hospitalier Pitié-Salpêtrière — Paris
• Centre hospitalier régional universitaire de de Tours — Tours

Испания · 5 центров

• Hospital del Mar — Barcelona
• University Hospital of Bellvitge — Barcelona
• Hospital Universitario La Paz - Carlos III — Madrid
• Clinical Hospital Santiago de Compostela — Santiago de Compostela
• Hospital Universitari i Politècnic La Fe — Valencia

Канада · 3 центра

• Genge Partners — Montreal
• University of Alberta — Edmonton
• McMaster University Medical Centre — Hamilton

Польша · 3 центра

• Centrum Medyczne Neuromed — Bydgoszcz
• Linden sp. z o. o. sp. k. — Krakow
• City Clinic Research Sp. z o.o. — Warsaw

Великобритания · 3 центра

• King's College Hospital — London
• MDN Centre Queen Square Institute of Neurology — London
• Royal Stoke University Hospital — Stoke-on-Trent

Израиль · 2 центра

• Hadassah Medical Center — Jerusalem
• Tel Aviv Sourasky Medical Center — Tel Aviv

Швеция · 2 центра

• Studieenheten Akademiskt specialistcentrum — Stockholm
• Umeå University Hospital — Umeå

Бельгия · 1 центр

• UZ Leuven — Leuven

Ирландия · 1 центр

• Trinity College Dublin — Dublin

Нидерланды · 1 центр

• UMC Utrecht — Utrecht

Идентификаторы

NCT: NCT07322003 · PL101-ALS301 / FNP254-CT-2501

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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