Evaluation of Effectiveness of ALBENDAZOLIVERMECTIN Coformulation vs ALBENDAZOLE for Treatment of Intestinal Worms

NCT05124691 | Terminated Phase 2 Results DMC

• 1 other identifier: ALIVE
• Study Type: interventional
• Target: 1,001
• Locations: 3 countries
• Sites: 3

Brief Summary

The purpose of this clinical trial is to evaluate a fixed-dose co-formulation (FDC) of ivermectin and albendazole for the treatment of all Soil Transmitted helminths (STH). The current strategy to control STH in endemic areas is mass administration of albendazole or mebendazole, mainly to pre-school and school-aged children. Although this treatment works well for some STH species, efficacy against Trichuris trichiura is poor and it is not effective Strongyloides stercoralis. Thus new drugs or drug combinations are an urgent priority to increase the effectiveness of control programmes. Furthermore, the World Health Organisation has recommended combination therapy of ivermectin with albendazole. The trial proposed, is an adaptive phase II/III trial where the phase II component will evaluate the safety of the FDC as a single dose or 3-day single dose regimen for the treatment of T. trichiura in paediatric population. After analysis of the safety results the phase III trial will be executed to evaluate the efficacy of the FDC as a single dose or 3-day single dose regimen compared to the standard single dose regimen of ALB (400 mg) for the treatment of T. trichiura, hookworm and S. stercoralis in paediatric and young adult population. The estimated total sample size for the adaptive design (phase II and III component) is 1223 participants. Of these, 126 will be enrolled in the phase II and 1097 in the phase III components respectively in an adaptive trial design.

Conditions

Helminthes; Infestation, Intestinal

Keywords

soil-transmitted helminths; pediatric; adult; albendazole; ivermectin; coformulation

Outcome Measures

Primary Outcomes (2)

• Cure Rate for T. Trichiura (CR)

  For Trichuris trichiura, the cure rate is defined as the proportion of participants who test negative for T. trichiura eggs in the Kato-Katz fecal examination on day 21 post-treatment, relative to the total number of participants infected at baseline (n=636).

  21 days

• Frequency of Related Adverse Events

  Proportions of participants presenting at least one treatment-related adverse event by arm

  21 days postreatment

Secondary Outcomes (6)

• Egg Reduction Rate for T. Trichiura (ERR)

  21 days

• Cure Rate for for Hookworm (CR)

  21 days

• Egg Reduction Rate for Hookworm (ERR)

  21 days

• Cure Rates for for S. Stercoralis

  21 days

• Cure Rate for T. Trichiura (CR) by qPCR

  21 days

Study Arms (3)

Albendazole

ACTIVE COMPARATOR

Albendazole 400 mg single dose

Drug: Albendazole

FDCx1. Albendazole and Ivermectin Fixed Dose Coformulation

EXPERIMENTAL

Single dose of a tablet of FDC 400mg18mg or 400mg9mg. (i) For participants \<45 kg of body weight at baseline: FDC of 400mg ALB 9mg IVM. (ii) For participants ≥45 kg of body weight at baseline: FDC of 400mg ALB18mg IVM

Combination Product: Albendazole and Ivermectin fixed dose coformulation

FDCx3. Albendazole and Ivermectin Fixed Dose Coformulation 3 days

EXPERIMENTAL

Daily dose of a tablet of FDC 400mg18mg or 400mg 9mg for 3 days. (i)For participants \<45 kg of body weight at baseline: FDC of 400mg ALB9mg IVM. (ii) For participants ≥45 kg of body weight at baseline: FDC of 400mg ALB 18mg IVM.

Combination Product: Albendazole and Ivermectin fixed dose coformulation

Interventions

Albendazole and Ivermectin fixed dose coformulation COMBINATION_PRODUCT

400 mg Albendazole - 9 mg Ivermectin OR 400 mg Albendazole - 18 mg Ivermectin

FDCx1. Albendazole and Ivermectin Fixed Dose Coformulation; FDCx3. Albendazole and Ivermectin Fixed Dose Coformulation 3 days

Albendazole DRUG

Albendazole 400mg single dose

Albendazole

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Positive infection test by microscopy for at least one of the following STH: T. trichiura, hookworms and/or larvae of S. stercoralis.
• Weight ≥15 Kg.
• Male or female, aged 5 to 18 years.
• Female participants who are ≥12 years old (or female post menarche) must have a negative urine pregnancy test at screening or at the time of randomization.
• Ability to take oral medication and willingness to comply with all study procedures.
• Parental acceptance to participate in the study by obtaining a signed and dated informed consent form approved by the Regulatory authorities. In addition, verbal assent will be obtained from children aged 12-18 years.

You may not qualify if:

• Intake of ALB, mebendazole and/or IVM, or any potentially interacting drug three months before screening.
• Residence outside the study area or planning to move away in the four weeks following recruitment.
• Epidemiological risk of infection by Loa loa.
• Serious medical illness, per investigator's criteria.
• Any participant's condition that would prevent the appropriate evaluation and followup, as per investigator's criteria.
• Known hypersensitivity to any components of either of the study treatment.
• Positive pregnancy urine test, pregnant or first week postpartum.

Sponsors & Collaborators

• Barcelona Institute for Global Health: lead
• Leiden University Medical Center: collaborator
• Bahir Dar University: collaborator
• Centro de Investigacao em Saude de Manhica: collaborator
• London School of Hygiene and Tropical Medicine: collaborator
• Kenya Medical Research Institute: collaborator
• Laboratorios Liconsa: collaborator
• Universidad de León: collaborator
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator

Study Sites (3)

Bahir Dar University, Colleges of Medicine and Health Sciences (BDU-CMHS)

Bahir Dar, P.O. Box 79, Ethiopia

Location

Kenya Medical Research Institute (KEMRI)

Nairobi, 54840-00200, Kenya

Location

Centro de Investigação em Saúde da Manhiça (CISM)

Manhiça, Maputo Province, 1929, Mozambique

Location

Related Publications (2)

• Krolewiecki A, Kepha S, Fleitas PE, van Lieshout L, Gelaye W, Messa A Jr, Gandasegui J, Algorta J, Novela V, de Jesus A, Rono M, Degarege D, Bedane D, Mwahanje J, Mandomando I, Mwandawiro C, Enbiale W, Munoz J; Stopping Transmission of Intestinal Parasites (STOP) consortium. Albendazole-ivermectin co-formulation for the treatment of Trichuris trichiura and other soil-transmitted helminths: a randomised phase 2/3 trial. Lancet Infect Dis. 2025 May;25(5):548-559. doi: 10.1016/S1473-3099(24)00669-8. Epub 2025 Jan 10.

  PMID: 39805305 DERIVED

• Krolewiecki A, Enbiale W, Gandasegui J, van Lieshout L, Kepha S, Messa Junior A, Bengtson M, Gelaye W, Escola V, Martinez-Valladares M, Cambra-Pelleja M, Algorta J, Marti-Soler H, Fleitas P, Ballester MR, Doyle SR, Williams NA, Legarda A, Mandomando I, Mwandawiro C, Munoz J. An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the treatment of Trichuris trichiura and other STH infections. ALIVE trial protocol. Gates Open Res. 2022 May 5;6:62. doi: 10.12688/gatesopenres.13615.1. eCollection 2022.

  PMID: 36540062 DERIVED

MeSH Terms

Conditions

Helminthiasis

Interventions

Albendazole; Ivermectin

Condition Hierarchy (Ancestors)

Parasitic Diseases; Infections

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Polyketides; Lactones

Limitations and Caveats

Pre-specified sample size for evaluating the efficacy of FDCx1 and FDCx3 versus albendazole for the treatment of S. stercoralis was not met, the available data were collected and summarized descriptively. These results are reported in Outcome Measure 6. However, due to the insufficient sample size, no formal statistical analysis was performed, and the findings are presented for descriptive purposes only.

Results Point of Contact

• Title: Jose Muñoz
• Organization: Instituto de Salud Global de Barcelona - ISGLOBAL

jose.munoz@isglobal.org

+34608774071

Study Officials

• Jose Munoz, MD, PhD

  Barcelona institue for Global health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2021
• First Posted: November 18, 2021
• Study Start: January 20, 2022
• Primary Completion: March 21, 2023
• Study Completion: March 24, 2023
• Last Updated: September 22, 2025
• Results First Posted: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Data is already available upon request to IDDO
• Access Criteria: All data sharing request received by IDDO will be addressed to the project consortium members who will approve/reject the data sharing based on the relevance of the proposal.

Locations

KE (1); MO (1); ET (1)