Oxfendazole in Mild Parenchymal Brain Cysticercosis

NCT ID: NCT06565507

Last Updated: 2024-11-01

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 544 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-15
• Study Completion Date: 2028-12-30

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.

Conditions

Brain Cysticercosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Intervention 1

OXF 20 mg/kg/d, single dose, orally

Group Type: EXPERIMENTAL

Oxfendazole single dose

Intervention Type: DRUG

Subjects will receive active oxfendazole, 20 mg/kg/day, orally, as a single dose. Oxfendazole placebo will be used at days 4 and 7 to maintain blinding between the two intervention arms.

Intervention 2

OXF 20 mg/kg/d, for three days (1, 4 and 7), orally

Group Type: EXPERIMENTAL

Oxfendazole three doses

Intervention Type: DRUG

Subjects will receive active oxfendazole, 20 mg/kg/day, orally, in three days (1, 4 and 7)

Comparison regimen

Combined treatment with albendazole (15 mg/k/d) plus praziquantel (50 mg/k/d), for 10 days, orally.

Group Type: ACTIVE_COMPARATOR

albendazole plus praziquantel regime

Intervention Type: DRUG

Subjects will receive a combination of albendazole plus praziquantel, as a standard treatment for brain cysticercosis (neurocysticercosis), orally, for ten days. Albendazole will be given at 15/kg/d and praziquantel at 50/kg/d.

Interventions

Oxfendazole single dose

Subjects will receive active oxfendazole, 20 mg/kg/day, orally, as a single dose. Oxfendazole placebo will be used at days 4 and 7 to maintain blinding between the two intervention arms.

Intervention Type: DRUG

Oxfendazole three doses

Subjects will receive active oxfendazole, 20 mg/kg/day, orally, in three days (1, 4 and 7)

Intervention Type: DRUG

albendazole plus praziquantel regime

Subjects will receive a combination of albendazole plus praziquantel, as a standard treatment for brain cysticercosis (neurocysticercosis), orally, for ten days. Albendazole will be given at 15/kg/d and praziquantel at 50/kg/d.

Intervention Type: DRUG

Other Intervention Names

Intervention 1; Intervention 2; Comparison regimen

Eligibility Criteria

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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oxfendazole Development Group

OTHER

Sponsor Role: collaborator

Universidad Peruana Cayetano Heredia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hector H Garcia, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Universidad Peruana Cayetano Heredia

Central Contacts

Hector H Garcia, MD, PhD

Role: CONTACT

hgarcia@jhsph.edu

+511 3287360

Javier A Bustos, MD, PhD

Role: CONTACT

javier.bustos.p@upch.pe

+511 3284038

Other Identifiers

211661

Identifier Type: -

Identifier Source: org_study_id