Clinical trial NCT06156566: European Trial Into Mpox Infection
Official title: European Randomised Clinical Trial on mPOX Infection
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Monkeypox
Keywords: tecovirimat
mpox
TPOXX
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: European Clinical Research Alliance for Infectious Diseases (ECRAID)
name: Erasmus Medical Center
name: Hospital Universitario La Paz
name: ANRS, Emerging Infectious Diseases
name: Universiteit Antwerpen
First posted: 2023-12-05
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this randomized controlled double-blind clinical trial is to test the drug tecovirimat in patients with mpox (previously known as monkeypox) disease.

The main questions it aims to answer are:

* Is tecovirimat effective in treating mpox infection.
* Is tecovirimat safe to treat patients with mpox infection.

Participants will receive either the drug tecovirimat orally, 600 mg twice per day, or a matching placebo. The outcome of the infection and the side effect experienced will be compared between the two groups.


Eligibility criteria: Inclusion Criteria:

* Polymerase Chain Reaction (PCR) /Nucleic Acid Amplification Test (NAAT) -confirmed mpox infection
* The presence of active skin or mucosal lesion(s)
* Signed Informed Consent Form

Exclusion Criteria:

* Age \<18 years.
* Body weight \<40 kg
* Pregnant and breastfeeding patients are not eligible for inclusion in this study.
* Lack of mental capacity to provide informed consent
* Trial participation is considered not in the best interest of patient
* Known hypersensitivity to the active substance or to any of the excipients of the study drug.
* Use of contraindicated treatment repaglinide. (Repaglinide, an oral treatment for diabetes mellitus, may be discontinued while taking study treatment with the agreement of the patient's general practitioner, who may start alternate diabetes treatment if considered necessary.)
* Previous, current or planned use of another investigational drug (tecovirimat) at any point during study participation.
* The patient's own doctor considers there to be a definite indication for the patient to receive tecovirimat or the local guidelines establish that tecovirimat treatment should be initiated
* The patient's own doctor considers there to be a definite contraindication to the patient receiving tecovirimat.
* The patient suffers from hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.

Primary outcomes:
measure: Time to complete mpox lesion resolution
timeFrame: 28 days
Secondary outcomes:
measure: Time to active lesion resolution
timeFrame: 28 days
measure: Status of the lesions on day 7, 14 and 28
timeFrame: Day 7, day 14 and day 28
measure: Time to resolution of symptoms
timeFrame: 90 days
measure: Occurrence of a negative monkeypox PCR of skin or mucosal swab
timeFrame: Days 7, 14 and 28
measure: Persistence of scars and skin discoloration
timeFrame: Assessed on day 90
measure: Change from baseline in quality of life
timeFrame: Assessed on day 14 and day 90.
measure: All-cause mortality
timeFrame: Assessed on day 28 and on day 90
measure: Time to complication or all-cause admission to hospital or all-cause death
timeFrame: Assessed within 28 days and within 90 days.
measure: Frequency of AEs, SAEs and SUSARs
timeFrame: Assessed within 28 days and within 90 days.
measure: Resolution of pain
timeFrame: Assessed on days 7, 14 and 90.
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Institute of Tropical Medicine
city: Brussels
country: Belgium
facility: Cliniques Universitaires St. Luc
city: Paris
country: France
facility: APHP St. Louis
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Milan
country: Italy
facility: Hospital Luigi Sacco
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona - AOUI Verona
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC - AMC
city: Oslo
country: Norway
facility: Oslo Unversity Hospital
city: Lisbon
country: Portugal
facility: Hospital de Santo António dos Capuchos
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
Study officials:
affiliation: UMC Utrecht
name: Miquel B Ekkelenkamp, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wedekind C. The infectivity, growth, and virulence of the cestode Schistocephalus solidus in its first intermediate host, the copepod Macrocyclops albidus. Parasitology. 1997 Sep;115 ( Pt 3):317-24. doi: 10.1017/s0031182097001406.
citation: Jang TJ, Lee JI, Kim JR, Kim DH, Bae SH. Decreased gastric proliferation of foveolar epithelial cells after the eradication of Helicobacter pylori. J Korean Med Sci. 1997 Oct;12(5):421-6. doi: 10.3346/jkms.1997.12.5.421.
citation: Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Statist Soc B 1995;57(1):289-300.
citation: Horton JA, Cruess DF, Romans MC. Compliance with mammography screening guidelines: 1995 Mammography Attitudes and Usage Study Report. Womens Health Issues. 1996 Sep-Oct;6(5):239-45. doi: 10.1016/1049-3867(96)00037-0. No abstract available.
citation: Zherbin EA, Chukhlovin AB. [Loss of specific membrane receptors during the interphase death of thymus cells]. Tsitologiia. 1984 Aug;26(8):973-7. Russian.
citation: Asaki S, Hatori S, Iwai S, Nishimura T, Sato A, Goto Y. Diagnosis of submucosal tumors by injecting a water soluble contrast medium: basic research and imaging of tumors. Tohoku J Exp Med. 1982 Oct;138(2):121-30. doi: 10.1620/tjem.138.121.
citation: EMA: An overview of Tecovirimat SIGA and why it is authorised in the EU. 31-May-2022: https://www.ema.europa.eu/en/documents/overview/tecovirimat-siga-epar-medicine-overview_en.pdf
citation: EMA: Summary of product characteristics: www.ema.europa.eu/en/documents/product-information/tecovirimat-siga-epar-product-information_en.pdf, accessed 6-9-2022
citation: Mock M, Miyada CG, Collier RJ. Genetic analysis of the functional relationship between colicin E3 and its immunity protein. J Bacteriol. 1984 Aug;159(2):658-62. doi: 10.1128/jb.159.2.658-662.1984.
citation: Grohmann M, Henseling M. Lack of differences between the neuronal and extraneuronal handling of 3H-7- and 3H-ring-2,5,6-(-)noradrenaline. Naunyn Schmiedebergs Arch Pharmacol. 1988 Aug;338(2):180-4. doi: 10.1007/BF00174867.
citation: Hoy SM. Tecovirimat: First Global Approval. Drugs. 2018 Sep;78(13):1377-1382. doi: 10.1007/s40265-018-0967-6.
citation: Howard G, Waller JL, Voeks JH, Howard VJ, Jauch EC, Lees KR, Nichols FT, Rahlfs VW, Hess DC. A simple, assumption-free, and clinically interpretable approach for analysis of modified Rankin outcomes. Stroke. 2012 Mar;43(3):664-9. doi: 10.1161/STROKEAHA.111.632935. Epub 2012 Feb 16.
citation: Jezek Z, Nakano JH, Arita I, Mutombo M, Szczeniowski M, Dunn C. Serological survey for human monkeypox infections in a selected population in Zaire. J Trop Med Hyg. 1987 Feb;90(1):31-8.
citation: Joint ECDC-WHO Regional Office for Europe Monkeypox Surveillance Bulletin, published 31-8-2022: monkeypoxreport.ecdc.europa.eu, accessed 6-9-2022
citation: Tritrakarn A. Pulmonary sequestration: ultrasonographic visualization of feeding artery. J Med Assoc Thai. 1989 Aug;72(8):465-8.
citation: Mitchell DL. The induction and repair of lesions produced by the photolysis of (6-4) photoproducts in normal and UV-hypersensitive human cells. Mutat Res. 1988 Nov;194(3):227-37. doi: 10.1016/0167-8817(88)90024-7.
citation: Karcioglu O, Topacoglu H, Dikme O, Dikme O. A systematic review of the pain scales in adults: Which to use? Am J Emerg Med. 2018 Apr;36(4):707-714. doi: 10.1016/j.ajem.2018.01.008. Epub 2018 Jan 6.
citation: Label FDA: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/214518s000lbl.pdf, accessed 6-9-2022
citation: McCullagh P. Regression models for ordinal data (with discussion). J R Statist Soc B. 1980;42:109-42.
citation: Germer A, Jahnke C, Mack A, Enzmann V, Reichenbach A. Modification of glutamine synthetase expression by mammalian Muller (glial) cells in retinal organ cultures. Neuroreport. 1997 Sep 29;8(14):3067-72. doi: 10.1097/00001756-199709290-00012.
citation: Wienberg J, Stanyon R, Nash WG, O'Brien PC, Yang F, O'Brien SJ, Ferguson-Smith MA. Conservation of human vs. feline genome organization revealed by reciprocal chromosome painting. Cytogenet Cell Genet. 1997;77(3-4):211-7. doi: 10.1159/000134579.
citation: Pittman PR, Martin JW, Kingebeni PM, Tamfum J-JM, Wan Q, Reynolds MG, et al. Clinical characterization of human monkeypox infections in the Democratic Republic of the Congo. medRxiv. 2022:2022.05.26.22273379.
citation: Product Development Under the Animal Rule - Guidance for Industry, FDA October 2015: https://www.fda.gov/media/88625/download, accessed 6-9-2022
citation: Kuznetsov VG. [Contamination of vegetables and the external environment of vegetable store houses of the Primor'e Territory by Yersinia]. Gig Sanit. 1986 May;(5):69-71. No abstract available. Russian.
citation: Sale TA, Melski JW, Stratman EJ. Monkeypox: an epidemiologic and clinical comparison of African and US disease. J Am Acad Dermatol. 2006 Sep;55(3):478-81. doi: 10.1016/j.jaad.2006.05.061.
citation: Siegrist EA, Sassine J. Antivirals With Activity Against Mpox: A Clinically Oriented Review. Clin Infect Dis. 2023 Jan 6;76(1):155-164. doi: 10.1093/cid/ciac622.
citation: Cushing M. Who's responsible for too-early discharge? Am J Nurs. 1989 Apr;89(4):471-2. No abstract available.
citation: Tarin-Vicente EJ, Alemany A, Agud-Dios M, Ubals M, Suner C, Anton A, Arando M, Arroyo-Andres J, Calderon-Lozano L, Casan C, Cabrera JM, Coll P, Descalzo V, Folgueira MD, Garcia-Perez JN, Gil-Cruz E, Gonzalez-Rodriguez B, Gutierrez-Collar C, Hernandez-Rodriguez A, Lopez-Roa P, de Los Angeles Melendez M, Montero-Menarguez J, Munoz-Gallego I, Palencia-Perez SI, Paredes R, Perez-Rivilla A, Pinana M, Prat N, Ramirez A, Rivero A, Rubio-Muniz CA, Vall M, Acosta-Velasquez KS, Wang A, Galvan-Casas C, Marks M, Ortiz-Romero PL, Mitja O. Clinical presentation and virological assessment of confirmed human monkeypox virus cases in Spain: a prospective observational cohort study. Lancet. 2022 Aug 27;400(10353):661-669. doi: 10.1016/S0140-6736(22)01436-2. Epub 2022 Aug 8.
citation: Thornhill JP, Barkati S, Walmsley S, Rockstroh J, Antinori A, Harrison LB, Palich R, Nori A, Reeves I, Habibi MS, Apea V, Boesecke C, Vandekerckhove L, Yakubovsky M, Sendagorta E, Blanco JL, Florence E, Moschese D, Maltez FM, Goorhuis A, Pourcher V, Migaud P, Noe S, Pintado C, Maggi F, Hansen AE, Hoffmann C, Lezama JI, Mussini C, Cattelan A, Makofane K, Tan D, Nozza S, Nemeth J, Klein MB, Orkin CM; SHARE-net Clinical Group. Monkeypox Virus Infection in Humans across 16 Countries - April-June 2022. N Engl J Med. 2022 Aug 25;387(8):679-691. doi: 10.1056/NEJMoa2207323. Epub 2022 Jul 21.
citation: WHO fact sheet: www.who.int/news-room/fact-sheets/detail/monkeypox, accessed 6-9-2022
citation: I.G. stimulants of the central nervous system. Behav Neuropsychiatry. 1975 Apr-1976 Mar;7(1-12):79-80. No abstract available.