Efavirenz for the Treatment of Creutzfeldt-Jakob Disease

Официальное название

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Clinical Study to Evaluate the Efficacy and Safety of Efavirenz in Patients With Creutzfeldt-Jakob Disease

Обзор

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial designed to evaluate the efficacy and safety of efavirenz in patients with Creutzfeldt-Jakob disease (CJD). A total of 246 eligible participants will be enrolled across 21 study centers nationwide. Participants will be randomly assigned in a 1:1 ratio to receive either efavirenz or placebo. Participants in the efavirenz group will receive 200 mg once daily at bedtime for the first week, followed by an increased dose of 400 mg once daily thereafter. Participants in the placebo group will receive matching placebo tablets using the same dosing schedule. Treatment will be administered under double-blind conditions and will continue until death or study completion. During the study, all participants will receive monthly telephone follow-up assessments starting from treatment initiation to evaluate long-term efficacy and safety, continuing until death or study termination. The primary objective of the study is to determine whether efavirenz can prolong survival in patients with CJD. The primary endpoint is median survival time from randomization to death. Secondary endpoints include assessment of the effect of efavirenz on the rate of functional decline and treatment tolerability. Adverse events (AEs) and serious adverse events (SAEs) will be recorded and evaluated for frequency, severity, outcomes, and their relationship to the study drug. Key inclusion criteria include adults aged 18 to 80 years of either sex with a baseline MRC-Prion Disease Rating Scale (MRC-PDRS) score greater than 10 and the availability of a reliable caregiver to support study participation. Key exclusion criteria include the presence of other serious or life-threatening illnesses, use of medications contraindicated with efavirenz that cannot be adjusted, and pregnancy or breastfeeding. Written informed consent will be obtained from all participants or their legally authorized representatives prior to enrollment.

Вмешательства

• Препарат Efavirenz
  The study drug in this trial is Efavirenz, and the control is a matching placebo. Efavirenz is supplied as 200 mg film-coated tablets. The placebo tablets are identical in appearance, color, and size to the Efavirenz tablets but contain no active ingredient. The main excipients of the placebo include lactose, microcrystalline cellulose, cross-linked sodium carboxymethyl cellulose, hydroxypropyl cellulose, sodium lauryl sulfate, purified water, Opadry, and an enteric film-coating premix. Both Efa
• Препарат Placebo
  The study drug in this trial is Efavirenz, and the control is a matching placebo. Efavirenz is supplied as 200 mg film-coated tablets. The placebo tablets are identical in appearance, color, and size to the Efavirenz tablets but contain no active ingredient. The main excipients of the placebo include lactose, microcrystalline cellulose, cross-linked sodium carboxymethyl cellulose, hydroxypropyl cellulose, sodium lauryl sulfate, purified water, Opadry, and an enteric film-coating premix. Both Efa

Первичные конечные точки

• Median survival time [Срок оценки: From randomization to death, assessed up to 36 months]

Вторичные конечные точки (4)

• Time to Loss of Independent Feeding Ability [Срок оценки: From randomization until the feeding item in the Barthel Index first reaches 0, assessed up to 36 months]
• Time to Loss of Bowel and Bladder Control [Срок оценки: From randomization until both bowel and bladder control items in the Barthel Index first reach 0, assessed up to 36 months]
• Time to Development of Akinetic Mutism [Срок оценки: From randomization until the patient meets criteria for akinetic mutism, assessed up to 36 months]
• Changes in MRC-PDRS and Barthel Index Scores [Срок оценки: From randomization to each monthly follow-up assessment, assessed every month up to 36 months]

Критерии участия

Критерии включения

• Patients who meet the World Health Organization (WHO) diagnostic criteria for probable sporadic CJD or have a genetically confirmed diagnosis of hereditary CJD.
• Age 18-80 years, any sex.
• Baseline score on the Medical Research Council Prion Disease Rating Scale (MRC-PDRS) >10 (i.e., retaining some functional ability).
• The patient has a caregiver aged ≥18 years who can accompany the patient during the study and assist in providing relevant information.
• The patient or their legally authorized representative has signed the informed consent form.

Критерии исключения

• Presence of severe somatic diseases or unstable clinical conditions that may affect study compliance or patient safety, including malignancy, advanced liver or kidney dysfunction, severe cardiac disease (including patients with a history of significant QTc prolongation).
• Current use of drugs that are known contraindications with efavirenz and cannot be discontinued or substituted.
• Female participants who are pregnant or breastfeeding.
• Other medical or psychiatric conditions, as judged by the investigator, that may interfere with the patient's participation in or completion of the study.

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

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Xuanwu Hospital, Capital Medical University — Пекин

Публикации

• Lerner AJ, Arnold SE, Maxfield E, Koenig A, Toth ME, Fortin B, Mast N, Trombetta BA, Denker J, Pieper AA, Tatsuoka C, Raghupathy S, Pikuleva IA. CYP46A1 activation by low-dose efavirenz enhances brain cholesterol metabolism in subjects with early Alzheimer's disease. Alzheimers Res Ther. 2022 Dec 29;14(1):198. doi: 10.1186/s13195-022-01151-z. PMID 36581878
• Ali T, Hannaoui S, Nemani S, Tahir W, Zemlyankina I, Cherry P, Shim SY, Sim V, Schaetzl HM, Gilch S. Oral administration of repurposed drug targeting Cyp46A1 increases survival times of prion infected mice. Acta Neuropathol Commun. 2021 Apr 1;9(1):58. doi: 10.1186/s40478-021-01162-1. PMID 33795005

Идентификаторы

NCT: NCT07482085 · 临研审[2026]009号-002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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