Efavirenz for the Treatment of Creutzfeldt-Jakob Disease

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

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 Overview

• Status: Not yet recruiting
• Conditions: Creutzfeldt-Jakob Disease
• Intervention / Treatment: Drug: Efavirenz; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 246
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zhongyun Chen, MD; Phone Number: +86-10-1365-100-6467; Email: chenzhongyun3@163.com

Study Locations

• China
  • Beijing, China, 100053
    • Xuanwu Hospital, Capital Medical University
    • Contact: Yan Yin; Phone Number: 010-83199270; Email: xwkxsc@163.com
    • Principal Investigator: Liyong Wu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Efavirenz Treatment Arm; Participants will receive oral efavirenz at a dose of 200 mg once daily (1 tablet per dose). After 1 week of continuous treatment, the dose will be increased to 400 mg once daily (2 tablets per dose). To reduce central nervous system-related adverse effects, administration at bedtime is recommended. Participants will continue study treatment under double-blind conditions from the time of randomization until the primary study endpoint is reached or the study is completed.	Drug: 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 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.
Placebo Comparator: Placebo Control Arm; Participants will receive oral placebo tablets that are identical in appearance, color, and size to efavirenz tablets at a dose of 200 mg once daily (1 tablet per dose). After 1 week of continuous treatment, the dose will be increased to 400 mg once daily (2 tablets per dose). Participants will continue study treatment until the primary study endpoint is reached or the study is completed. All other treatment procedures and conditions will be the same as those applied in the efavirenz treatment arm.	Drug: 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 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median survival time	The median number of days from randomization to death	From randomization to death, assessed up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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)	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)	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	From randomization to each monthly follow-up assessment, assessed every month up to 36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Incidence, severity, and outcomes of adverse events (AEs) and serious adverse events (SAEs) will be recorded and analyzed, including assessment of their potential relationship to the study treatment. Safety information will be collected through monthly telephone follow-up interviews with the patient or caregiver	From randomization until the end of the study, assessed up to 36 months

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: March 6, 2026
• First Submitted That Met QC Criteria: March 15, 2026
• First Posted (Actual): March 19, 2026

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 15, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: efavirenz; Creutzfeldt-Jakob disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Infections; Neurocognitive Disorders; Dementia; Central Nervous System Infections; Prion Diseases; Creutzfeldt-Jakob Syndrome; efavirenz
• Other Study ID Numbers: 临研审[2026]009号-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The results of this study will be summarized promptly after study completion, with consideration given to publication in academic journals. Any publication will adhere to ICMJE guidelines regarding authorship and disclosure of conflicts of interest. Regardless of whether the study results are positive or negative, they will be reported on public platforms (e.g., updates on the Chinese Clinical Trial Registry). Data sharing will follow the policies of the Beijing Hospital Authority and the sponsor. Reasonable requests from researchers for data sharing will be considered, and anonymized data may be provided as appropriate, ensuring the confidentiality of participants' personal information.

Before any paper or report is published, no participant may disclose interim results or unpublished data without the sponsor's permission, to avoid misinterpretation of the findings. Published content will present aggregate data only, without revealing individual identities.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No