A Study to Investigate the Efficacy, Safety and Tolerability of Votoplam in Participants With Huntington's Disease

Официальное название

A Randomized, Placebo-controlled, Double-blind Phase 3 Study to Evaluate the Efficacy, Safety and Tolerability of Votoplam in Participants With Huntington's Disease

Обзор

The purpose is to assess safety and tolerability of votoplam and to determine whether votoplam slows disease progression in patients with early symptomatic Huntington's disease (HD) compared to the control arm. HTT227 - current compound code (former code is PTC518 from PTC Therapeutics), HTT227 is Novartis code under Novartis sponsorship.

Подробное описание

This study will have a variable double-blind treatment duration of up to 36 months. As part of the study design, not every participant will complete 36 months of treatment.

The study consists of 3 periods:

* Screening Period: A period of up to 42-days to assess participants eligibility * Double-blind Treatment Period: This period will have variable individual treatment duration, up to 36 months. The double-blind treatment period concludes when ≥50% patients complete Month 36. The maximum treatment duration for an individual participant is 36 months. * Safety Follow-up Period: A period consisting of one safety follow-up visit, conducted on site or by phone call, for all participants not continuing treatment in the separate open-label extension study or discontinuing early. The visit/phone call will take place 30 days after End of Study (EOS)

Вмешательства

• Препарат Votoplam (blinded)
  Votoplam (blinded) active treatment
• Препарат Placebo
  Placebo

Первичные конечные точки

• Change from Baseline in cUHDRS score [Срок оценки: Baseline, Month 36]

Вторичные конечные точки (9)

• Change from Baseline in UHDRS-TFC [Срок оценки: Baseline, Month 36]
• Change from Baseline in UHDRS-IS [Срок оценки: Baseline, Month 36]
• The time to decline in TFC score by at least one or IS score by at least 10 [Срок оценки: Baseline to end of treatment up to 36 months]
• Change from Baseline in UHDRS-TMS [Срок оценки: Baseline, Month 36]
• Change from Baseline in SDMT [Срок оценки: Baseline, Month 36]
• Change from Baseline in SWRT [Срок оценки: Baseline, Month 36]
• Percent change from Baseline in blood mHTT protein [Срок оценки: Baseline to steady state and up to 36 months in blood mHTT protein]
• Change from Baseline in serum NfL [Срок оценки: Baseline, Month 36]
• Incidence and severity of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and TEAEs leading to participant withdrawal [Срок оценки: Baseline to up to 36 months]

Критерии участия

Критерии включения

• Signed informed consents must be obtained prior to participation in the study
• Ambulatory male or female participants between 21 to 70 years of age, inclusive, on the day of Informed Consent signature
• Genetically confirmed HD diagnosis with a cytosine-adenine-guanine (CAG) repeat length of 40 or above. Participants must have prior genetic confirmation and known CAG repeat length obtained prior to screening.
• Meets all of the following criteria:

• UHDRS IS score ≥90
• UHDRS TFC score = 13
• UHDRS TMS score = 7-25, inclusive
• CAP100 ≥ 70 Calculation: CAP = Age at study entry × (CAG length - 30) / 6.49

Критерии исключения

• History of gene therapy or cell transplantation or any other experimental brain surgery for the treatment of HD
• Serologic evidence for active viral hepatitis as indicated by:

• positive anti-HBc IgM
• positive anti-HBc IgG confirmed by positive HBsAg and/or HBV DNA
• positive HCV ab test confirmed by positive HCV RNA
• Immunodeficiency diseases, including a positive human immunodeficiency virus (HIV) test result
• History or current diagnosis of ECG or cardiac abnormalities indicating significant risk of safety for participants such as:

• Concomitant clinically significant cardiac arrhythmias, e.g., sustained ventricular tachycardia, and clinically significant second- or third-degree AV block without a pacemaker
• History of familial long QT syndrome or known family history of Torsade de Pointes
• Women of childbearing potential, defined as all women physiologically capable of becoming pregnant from menarche until becoming post-menopausal, unless they have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral salpingectomy at least six weeks before taking study treatment. In the case of oophorectomy alone, the reproductive status of the woman needs to have been confirmed by follow-up hormone level assessment.

o WOCBP are excluded unless they are using highly effective methods of contraception (failure rate < 1% per year) while taking study treatment and for 8 months after stopping study treatment.

• Pregnant or nursing (breastfeeding) women

Other protocol defined inclusion/exclusion criteria may apply

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 · 25 центров

• University of CA San Diego — La Jolla
• Stanford Healthcare — Stanford
• CenExcel Rocky Mtn Clin Research — Englewood
• Georgetown University — Washington D.C.
• University Of South Florida — Tampa
• Parkinsons-Movement Disorder Ctr — Chicago
• Indiana University Health — Indianapolis
• University of Iowa Health Care — Iowa City
• … и ещё 17 центров

Великобритания · 8 центров

• Novartis Investigative Site — Exeter
• Novartis Investigative Site — Aberdeen
• Novartis Investigative Site — Cambridge
• Novartis Investigative Site — Cardiff
• Novartis Investigative Site — Glasgow
• University College Hospital — London
• Novartis Investigative Site — Oxford
• Southampton General Hospital — Southampton

Канада · 3 центра

• North York General Hospital — North York
• Centre de recherche du CHUM — Montreal
• CUSM Montreal Neurological Institute — Montreal

South Korea · 3 центра

• Novartis Investigative Site — Dongjak Gu
• Novartis Investigative Site — Seoul
• Novartis Investigative Site — Busan

Аргентина · 2 центра

• Novartis Investigative Site — CABA
• Novartis Investigative Site — CABA

Китай · 2 центра

• West China Hospital of Sichuan Uni — Чэнду
• Novartis Investigative Site — Ханчжоу

Франция · 2 центра

• Novartis Investigative Site — Bordeaux
• Novartis Investigative Site — Montpellier

Швейцария · 2 центра

• Novartis Investigative Site — Basel
• Novartis Investigative Site — Muri bei Bern

Тайвань · 2 центра

• Novartis Investigative Site — Changhua
• Novartis Investigative Site — Taipei

Австралия · 1 центр

• Novartis Investigative Site — Caulfield South

Израиль · 1 центр

• Tel Aviv Sourasky Med Ctr Ichilov — Tel Aviv

Идентификаторы

NCT: NCT07326709 · CHTT227A12301

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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