Efavirenz for the Treatment of Creutzfeldt-Jakob Disease

NCT07482085 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 临研审[2026]009号-002
• Study Type: interventional
• Target: 246
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Creutzfeldt-Jakob Disease

Keywords

Creutzfeldt-Jakob disease; efavirenz

Outcome Measures

Primary Outcomes (1)

• Median survival time

  The median number of days from randomization to death

  From randomization to death, assessed up to 36 months

Secondary Outcomes (4)

• Time to Loss of Independent Feeding Ability

  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

  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

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

• Changes in MRC-PDRS and Barthel Index Scores

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

Other Outcomes (1)

• Adverse Events

  From randomization until the end of the study, assessed up to 36 months

Study Arms (2)

Efavirenz Treatment Arm

EXPERIMENTAL

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

Placebo Control Arm

PLACEBO COMPARATOR

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

Interventions

Efavirenz DRUG

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.

Efavirenz Treatment Arm

Placebo DRUG

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 Control Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Xuanwu Hospital, Beijing: lead

Study Sites (1)

Xuanwu Hospital, Capital Medical University

Beijing, 100053, China

Location

Related Publications (2)

• 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 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Creutzfeldt-Jakob Syndrome

Interventions

efavirenz

Condition Hierarchy (Ancestors)

Prion Diseases; Central Nervous System Infections; Infections; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Zhongyun Chen, MD

CONTACT

+86-10-1365-100-6467; chenzhongyun3@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2026
• First Posted: March 19, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)