Efavirenz for the Treatment of Creutzfeldt-Jakob Disease

Phase 3Not Yet RecruitingNCT07482085

Xuanwu Hospital, Beijing246 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Interventions

EfavirenzDRUG

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 Efavirenz and placebo tablets are manufactured and supplied uniformly by the sponsor and dispensed in identical packaging with matching label numbers. The distribution and administration of the study drugs follow a double-blind procedure to ensure that neither investigators nor participants can determine the group assignment based on the appearance of the tablets, thereby maintaining blinding throughout the study.

PlaceboDRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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.

Outcomes

Primary Outcomes

Median survival time

The median number of days from randomization to death

Time frame: From randomization to death, assessed up to 36 months

Secondary Outcomes

Time to Loss of Independent Feeding Ability

Time from randomization to the first occurrence of loss of independent feeding ability, defined as the first time the feeding item in the Barthel Index drops to 0 (days)

Time frame: 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

Time from randomization to the first occurrence of loss of bowel and bladder control, defined as the first time both "bowel control" and "bladder control" items in the Barthel Index drop to 0 (days)

Time frame: 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

Time from randomization to the onset of akinetic mutism, defined as the time at which the patient is independently assessed and jointly confirmed by two investigators to have no spontaneous movements but maintains a sleep-wake cycle (days)

Time frame: From randomization until the patient meets criteria for akinetic mutism, assessed up to 36 months

Changes in MRC-PDRS and Barthel Index Scores

Changes in functional assessment scores from randomization to each pre-specified follow-up time point, including MRC-PDRS scores and Barthel Index scores, assessed monthly via telephone follow-up interviews with the patient or caregiver

Time frame: From randomization to each monthly follow-up assessment, assessed every month up to 36 months