Trial of treatment for monkeypox begins in the Democratic Republic of the Congo

press release

Wednesday 12 October 2022

NIH partnership with INRB to evaluate Tecovirimat (TPOXX).

A clinical trial evaluating the antiviral drug Tecovirimat, also known as TPOXX, in adults and children with monkeypox has begun in the Democratic Republic of the Congo (DRC). The study will evaluate the drug’s safety and its ability to relieve monkeypox symptoms and prevent serious outcomes, including death. The National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health, and the National Institute for Biomedical Research (INRB) of the Democratic Republic of the Congo are co-leading the study as part of the PALM government-government partnership. The collaborating institutions include the US Centers for Disease Control and Prevention (CDC), the Antwerp Institute for Tropical Medicine, the aid organization Alliance for International Medical Action (ALIMA) and the World Health Organization (WHO).

TPOXX, manufactured by pharmaceutical company SIGA Technologies, Inc. (New York), is approved by the US Food and Drug Administration for the treatment of smallpox. The drug inhibits the spread of viruses in the body by preventing virus particles from leaving human cells. The drug targets a protein found on both the virus that causes smallpox and the monkeypox virus.

“Monkeypox has caused a high burden of disease and death among children and adults in the Democratic Republic of the Congo, and improved treatment options are urgently needed,” said NIAID Director Anthony S. Fauci, MD. “This clinical study will provide important information on the safety and efficacy of tecovirimat in monkeypox. I would like to thank our scientific partners in the Democratic Republic of the Congo and the Congolese people for their continued collaboration in advancing this important clinical research.”

Since the 1970s, monkeypox virus has caused sporadic cases and outbreaks, mainly in the rainforest areas of Central and West Africa. Since May 2022, an outbreak of monkeypox has been taking place across several continents in areas where the disease is not endemic, including Europe and the United States, with most cases occurring in men who have sex with men. The outbreak has led to the recent declarations of public health emergency by the WHO and the US Department of Health and Human Services. From January 1, 2022 to October 5, 2022, the WHO has reported 68,900 confirmed cases and 25 deaths from 106 countries, regions and territories.

According to the WHO, the cases identified as part of the ongoing global outbreak are largely caused by the monkeypox virus clade IIb. Clade I, which is estimated to cause more severe disease and mortality than clade IIa and clade IIb, especially in children, is responsible for infections in the Democratic Republic of the Congo. The Africa Centers for Disease Control and Prevention (Africa CDC) has reported 3,326 cases of monkeypox (165 confirmed; 3,161 suspected) and 120 deaths in the Democratic Republic of the Congo from January 1, 2022 to September 21, 2022.

Humans can contract monkeypox through contact with infected animals, such as rodents or nonhuman primates, or humans. The virus can be transmitted between people through direct contact with skin lesions, body fluids, and respiratory droplets, including through intimate and sexual contact; and through indirect contact with contaminated clothing or bedding. Monkeypox can cause flu-like symptoms and painful skin lesions. Complications can include dehydration, bacterial infections, pneumonia, encephalitis, sepsis, eye infections, and death.

The study will enroll up to 450 adults and children weighing at least 3 kilograms (kg) with laboratory-confirmed monkeypox infection. Pregnant women can also register. Volunteers will be randomized to receive either tecovirimat or placebo oral capsules twice daily for 14 days, with the dose administered depending on the participant’s weight. The study is double-blind, so participants and investigators do not know who will receive tecovirimat or placebo.

All participants stay in a hospital for at least 14 days, where they receive supportive care. Study physicians will regularly monitor participants’ clinical status throughout the study, and participants will be asked to provide blood samples, throat swabs, and swabs from skin lesions for laboratory testing. The study is primarily designed to compare the mean time to healing of skin lesions in those who received tecovirimat versus those who received placebo. Investigators will also collect data on several secondary objectives, including comparisons of how quickly participants test negative for monkeypox blood in their blood, overall disease severity and duration, and between-group mortality.

Participants will be discharged from the hospital once all lesions have crusted over or flaked off and they have tested negative for monkeypox virus in their blood for two days in a row. You will be followed up for at least 28 days and asked to return at 58 days for an optional study visit for additional clinical and laboratory testing. An independent data and safety monitoring board will monitor the safety of participants throughout the duration of the study.

The study is being led by co-principal investigators Jean-Jacques Muyembe-Tamfum, MD, Ph.D., Director General of the INRB and Professor of Microbiology at Kinshasa University Medical School in Gombe, Kinshasa; and Placide Mbala, MD, Ph.D., operations director of the PALM project and director of the Division of Epidemiology and Pathogen Genomic Laboratory at the INRB.

“I am pleased that monkeypox is no longer a neglected disease and that this study will soon enable us to prove that there is an effective treatment for this disease,” said Dr. Muyembe Tamfum.

For more information, see clinicaltrials.gov and search identifier NCT05559099. The test schedule depends on the sign-up pace. A separate NIAID-sponsored study of TPOXX is ongoing in the United States. For information on the US study, visit the AIDS Clinical Trials Group (ACTG) website and search for TPOXX or Study A5418.

PALM is short for “Pamoja Tulinde Maisha,” a Swahili phrase that translates to “saving lives together.” NIAID and the Ministry of Health of the Democratic Republic of the Congo formed the clinical research partnership PALM in response to the 2018 Ebola outbreak in eastern DRC. The collaboration continued as a multilateral clinical research program composed of NIAID, the DRC Ministry of Health, INRB and INRB’s partners. PALM’s first study was the randomized controlled trial of multiple therapeutics for Ebola virus disease that supported regulatory approvals of NIAID-developed mAb114 (Ebanga) and REGN-EB3 (Inmazeb, developed by Regeneron) treatments.

NIAID conducts and supports research—at the NIH, in the United States, and worldwide—to study the causes of infectious and immune-mediated diseases and to develop better ways to prevent, diagnose, and treat these diseases. Press releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH):
NIH, the country’s medical research agency, comprises 27 institutes and centers and is part of the US Department of Health and Human Services. The NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research investigating the causes, treatments, and cures for common and rare diseases. For more information about the NIH and its programs, visit www.nih.gov.

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