Oxfendazole in Mild Parenchymal Brain Cysticercosis

Phase 2

Not yet recruiting

• Conditions: Brain Cysticercosis
• Interventions: Drug: Oxfendazole single dose; Drug: Oxfendazole three doses; Drug: albendazole plus praziquantel regime

• Registration Number: NCT06565507
• Lead Sponsor: Universidad Peruana Cayetano Heredia

Brief Summary

The goal of this clinical trial is to compare a single and multiple dose regimens of oxfendazole with the standard treatment in patients with mild (one or two lesions) parenchymal brain cisticercosis. The main question it aims to answer is if OXF will enhance clearance of brain parasites and therefore provide greater cysticidal efficacy, with the potential to provide a single-dose therapy for this type of NCC.

The study cohort will also allow us to identify early imaging markers that predict lesion resolution, as well as factors associated with residual calcification or focal gliosis after lesion resolution. This study will also provide additional information on the safety of the study interventions.

Detailed Description

This three-arm randomized controlled phase II/III clinical trial will compare the efficacy and safety of a single-dose regimen with 20 mg/kg oxfendazole and a regimen with three similar doses spread over seven days (day 1, day 4 and day 7), with the most effective antiparasitic regimen available, combined albendazole plus praziquantel for ten days in individuals with mild NCC (with one to two lesions).

Participants will receive treatment with oxfendazole (one or three dose regimens) or the standard treatment (albendazole + praziquantel). At day 15 after treatment onset, an MRI will be perfomed to evaluate early predictors of lesion resolution. MRI at day 90 will serve to evaluate efficacy (lesion resolution) and a day 180 MRI will evaluate sequelar lesions. CT will be perfomed at the en of the study to confirm persistence of calcified sequelar lesion.

The study will enroll 544 patients with viable or degenerating parenchymal NCC with no more than two lesions, all in a single brain area. Lesions can be one or two adjacent, viable or degenerating NCC lesions. Patients with only calcified lesions will not be included even if they show perilesional contrast enhancement.

Study Timeline

• Status Verified: 2024-06
• Study First Submitted: 2024-08-12
• Study First Submitted QC: 2024-08-19
• Study First Posted: 2024-08-22
• Last Update Submitted: 2024-10-30
• Last Update Posted: 2024-11-01
• Study Start: 2024-12-15
• Primary Completion: 2028-03-30
• Study Completion: 2028-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 544

Inclusion Criteria

1. Male or female individuals between 12 and 75 years of age, with suspected viable or degenerating intraparenchymal brain cysticercosis on neuroimaging (CT or MRI) and fulfill the diagnostic criteria for solitary cysticercus granuloma (Rajshekhar and Chandy, 1997)
2. If female of child-bearing potential and men, willing to use an adequate method of contraception*, including implants, injectables, combined oral contraceptives, effective intrauterine devices, sexual abstinence, or vasectomized partner while participating in the study.
3. Patients with normal laboratory values for hemoglobin, platelet counts, total white blood cells, glucose, creatinine, bilirubin, ALT, and AST.
4. Availability to grant informed consent if you are over 18 years of age or assent if you are a minor between 12 and 17 years of age.

Exclusion Criteria

1. Multiple lesion sites or more than two adjacent lesions.
2. Suspected neurotuberculosis (Rajshekhar's criteria) [66,67]
3. More than two viable brain cysts.
4. Large brain cysts (> 3cm in diameter)
5. Subarachnoid neurocysticercosis or intraventricular
6. Untreated ocular cysticercosis
7. Previous therapy with ABZ (does not include patients who received single-dose 400 mg ABZ for intestinal parasites), or PZQ in the past twelve months.
8. Active pulmonary tuberculosis evidenced by a positive chest X-ray and positive sputum smears.
9. Systemic disease other than NCC that may affect therapy or short-term prognosis, including but not limited to chronic renal failure, hepatic insufficiency, cardiac failure, and steroid-dependent immune diseases.
10. Patients in unstable condition or with severe intracranial hypertension (ICH). Definition of severe ICH for this study would be the presence of headaches, nausea, and vomiting, and papilledema at fundoscopic examination.
11. Pregnancy
12. History of hypersensitivity to ABZ or PZQ
13. Concurrent treatment with cimetidine, ranitidine, or theophylline.
14. Chronic alcohol or drug abuse
15. Positive to Strongyloides infection
16. History of reported allergy to contrast substances used in MRI.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention 1	Oxfendazole single dose	OXF 20 mg/kg/d, single dose, orally
Intervention 2	Oxfendazole three doses	OXF 20 mg/kg/d, for three days (1, 4 and 7), orally
Comparison regimen	albendazole plus praziquantel regime	Combined treatment with albendazole (15 mg/k/d) plus praziquantel (50 mg/k/d), for 10 days, orally.

Primary Outcome Measures

Name	Time	Method
Efficacy: completely resolution or persistance only as small lesion remnants.	Three months after treatment onset	Proportion of participants whose lesions completely resolved or persist only as small lesion remnants (\<20% of the original lesion size).

Secondary Outcome Measures

Name	Time	Method
Clinical effectiveness: Seizure relapses.	In the initial 12 months after treatment	The frequency of seizure relapses in individuals whose lesions resolved compared to those who had remaining viable or degenerating lesions on month 3 MRI
Safety: Serious adverse events	In the initial 12 months after treatment	Proportion of participants in each group who develop serious or severe adverse events, and the numbers of adverse events per group