Tecovirimat (TPOXX) for Treatment of Mpox

Summary of recent changes

Updates as of December 10, 2024

On December 10, 2024, the National Institutes of Health, which ran the STOMP trial, announced that enrollment to the STOMP trial had been closed as of November 27, 2024. Oral tecovirimat is no longer available via the STOMP trial.

On September 13, 2024, a summary of data was published in NEJM Evidence describing more than 7,100 patients who were prescribed tecovirimat under the expanded access investigational new drug (EA-IND) protocol. Evaluation of the EA-IND data also informed the most recent updates to the EA-IND protocol (version 6.4).

On June 18, 2024, the EA-IND eligibility criteria for tecovirimat treatment for patients with mpox was revised. The current version of the EA-IND protocol is version 6.4 dated June 5, 2024. Refer to Section 2.0 of the protocol for the full list of eligibility criteria. The CDC Institutional Review Board (IRB) approved the protocol amendment on June 5, 2024 (see the approval letter). Protocol continuation was approved on June 20.

What's known about tecovirimat

• Initial analysis of data from two randomized clinical studies designed to assess the efficacy and safety of a 14-day course of tecovirimat in treating human mpox, PALM007 (NCT05559099) and STOMP (NCT05534984) became available in August and December 2024, respectively.
• They showed that tecovirimat was safe but the antiviral did not reduce the time to resolution of mpox lesions in participants who received tecovirimat compared to participants who received placebo.
• PALM007 study participants were adults and children with clade I mpox in the Democratic Republic of the Congo.
• STOMP-randomized study participants were in the U.S. and a few other countries with clade II outbreaks; they were non-pregnant and non-lactating adults with clade IIb mpox who did not have severe immunocompromise or severe mpox.
• The findings from these clinical trials suggest that most patients with mpox who do not have severe disease or risk factors for severe disease (e.g., severe immunocompromise) will recover with supportive care and pain management.
• The role of tecovirimat in treatment of mpox in patients with severe immunocompromise, including advanced HIV, has not been determined and requires additional clinical trials.
  

Tecovirimat access for certain patients with mpox

STOMP enrollment closed on November 27, 2024, based on the study's Data Safety and Monitoring Board recommendation to stop further enrollment of participants who were being randomized to tecovirimat or placebo. Oral tecovirimat is no longer available via the STOMP trial.

Providers with patients who meet EA-IND eligibility for tecovirimat treatment for mpox should contact their state, local, or territorial health departments to see if any previously deployed tecovirimat supply remains available within their jurisdiction.

Previously deployed supply of tecovirimat that still remains within expiry may be used for patients who meet EA-IND eligibility criteria. If there is no local supply, state, local, or territorial health departments should request tecovirimat on providers' behalf by calling the CDC Emergency Operations Center (EOC) at (770) 488-7100 or emailing poxvirus@cdc.gov. (This email box is monitored from 9 a.m. to 4 p.m. U.S. Eastern time on non-holiday weekdays). A clinical consultation with a CDC clinical duty officer regarding management of hospitalized patients can also be requested.

To facilitate access to tecovirimat, CDC holds an expanded access IND (EA-IND) protocol for the treatment of non-variola orthopoxvirus infections, including mpox, in adults and children who meet eligibility criteria. The compassionate use of tecovirimat is for patients with laboratory-confirmed or suspected mpox must meet the eligibility criteria as outlined in Section 2.0 of the protocol. This includes:

1. Patients with severely immunocompromised conditions, defined as:

• HIV with CD4 < 200 cells/mm³
• Leukemia or lymphoma
• Generalized malignancy
• Solid organ transplantation
• Therapy with alkylating agents within 180 days prior to mpox illness onset
• Taking antimetabolites within 180 days prior to mpox illness onset
• Having radiation therapy within 180 days prior to mpox illness onset
• Taking tumor necrosis factor inhibitors within 180 days prior to mpox illness onset
• Taking high-dose corticosteroids (equivalent of 20 mg or greater of prednisone for at least 14 days) within 90 days prior to mpox illness onset
• Being a recipient with hematopoietic stem cell transplant < 24 months post-transplant or ≥ 24 months but with graft-versus-host disease or disease relapse, or having autoimmune disease with immunodeficiency as a clinical component
• Other comparable severe immunocompromise

Patients with severe immunocompromise are known to be at high risk for protracted or life-threatening manifestations of mpox, regardless of disease severity at presentation.

2. Patients in the following categories:

• Those with active skin conditions that place them at higher risk for disseminated infection, defined as atopic dermatitis, active exfoliative skin condition(s), such as eczema, burns, impetigo, active varicella zoster virus infection, psoriasis, or Darier disease (keratosis follicularis)
• Pregnant or lactating patients, regardless of illness severity or underlying comorbidities at presentation
• Children (< 18 years) regardless of illness severity or underlying comorbidities at presentation

3. Patients with protracted or life-threatening manifestations of mpox at presentation, as defined by one of the following:

• Lesions affecting 25% or more of body surface that may be confluent, necrotic, and/or hemorrhagic in appearance or cause sepsis
• Disease resulting in airway compromise or affecting the nervous system
• Cardiac [e.g., myocarditis] and or neurologic disease [e.g., encephalitis] which might occur in a small number of patients with mpox
• Ocular or periorbital infection, regardless of the time since infection onset

For patients with protracted or life-threatening manifestations or at high risk for protracted or life-threatening manifestations of mpox due to severe immunocompromising conditions, tecovirimat treatment should be administered early in the course of illness along with supportive care and pain control. It is also reasonable to consider initiating tecovirimat treatment in these patients in combination with either IV cidofovir or oral brincidofovir (the prodrug of cidofovir) and/or Vaccinia Immune Globulin (VIGIV).

Because the full scope of protracted or life-threatening infections is not known at this time, tecovirimat may also be considered on a case-by-case basis for an unusual situation wherein the treating clinician can request consult with CDC to discuss the case and decide whether treatment under the EA-IND may potentially be beneficial. Such consideration is expected to be rare and intended for unusual situations associated with disease that could result in clear long-term sequelae, such as urethral stricture.

CDC's EA-IND provides umbrella regulatory coverage so that clinicians and facilities do not need to request and obtain their own INDs. To be covered under the EA-IND, the providers and affiliated facilities must register online as participating providers/sites.

Tecovirimat use under the EA-IND is also covered under the Public Readiness and Emergency Preparedness (PREP) Act, which provides liability immunity to qualified providers and compensation to eligible patients via the Countermeasures Injury Compensation Program (CICP).

Tecovirimat (TPOXX) IND online registry

Providers and affiliated facilities must be registered online as participating providers/sites under the CDC-held expanded access IND (EA-IND) protocol for tecovirimat.

The tecovirimat IND Online Registry allows for convenient, time-efficient, and secure completion and return of required EA-IND forms to CDC. View this Fact Sheet for an overview of the tecovirimat IND online registry process.

Tecovirimat EA-IND Protocol

• The current EA-IND protocol is version 6.4, updated June 5, 2024.
• On June 5, 2024, the CDC IRB approved a protocol amendment (version 6.4 updated June 5, 2024). Protocol continuation was approved on June 20.
• Clinicians, care facilities, and hospitals providing tecovirimat should immediately transition to the revised protocol (version 6.4 updated June 5, 2024).
• The protocol includes Instructions for mixing tecovirimat capsules with food or water (version 6.3 dated May 5, 2023): This patient instruction sheet explains how to open tecovirimat capsules and mix with food or water for infants and children who cannot swallow pills.

Healthcare providers will be responsible for completing the following forms

Required

Informed Consent Form (version 6.4 dated June 5, 2024): English | Spanish Obtain prior to treatment.

• Alternative Consent Forms that can be used to obtain informed consent:
  • Short Form (English) | Spanish
  • Written Summary (English) | Spanish
• FDA Form 1572: One signed 1572 and treating clinician's curriculum vitae per facility suffices for all tecovirimat treatments administered under the EA-IND at the same facility. Access the electronic form through the Tecovirimat IND Online Registry.
• Patient Intake Form (version 6.4 dated June 5, 2024): Baseline assessment. Access the electronic form through the Tecovirimat IND Online Registry.
• Clinical Outcome Form (version 6.4 dated June 5, 2024): Progress and outcome information post treatment. Access the electronic form through the Tecovirimat IND Online Registry.
• Serious Adverse Events: Per FDA requirement, report life-threatening or serious adverse events associated with tecovirimat by completing a PDF MedWatch Form and returning it to CDC via email (regaffairs@cdc.gov) within 72 hours of awareness or sooner, if possible. The PDF MedWatch Form can also be downloaded from the FDA website. Note: The MedWatch Form can only be viewed on the Adobe desktop app. Please save or download the form for viewing.

Optional

• Lesion specimens for resistance testing: Lesion specimens may be sent to CDC for tecovirimat-treated patients with persistent lesions and/or any new lesions that develop during and/or after tecovirimat treatment to assess for development of antiviral resistance mutations. See Optional Lesion Specimens to CDC for Resistance Testing (version 6.3 dated May 5, 2023) for instructions on collection, storage, and submission of samples.
• Pharmacokinetic samples for testing: During tecovirimat treatment, plasma samples may be collected to monitor tecovirimat levels for adequate drug exposure in patients. Optional Pharmacokinetic Samples for Testing (version 6.3 dated May 5, 2023) has instructions on collection, storage, and submission of samples.

Institutional Review Board (IRB) Approval of Tecovirimat IND Protocol

• CDC IRB serves as the central IRB for review and approval. Facilities may elect to rely on the CDC IRB for centralized review and approval by submitting a request to the CDC's Human Research Protection Office within 7 calendar days of tecovirimat treatment at your facility. CDC will promptly document an agreement in writing using the CDC IRB Authorization Agreement (Sample Template), which must be signed by both parties.
• Facilities that elect to obtain their own IRB review must ensure compliance with applicable FDA regulations related to the tecovirimat EA-IND protocol. Note the posted tecovirimat EA-IND protocol and attachments must be used without any changes being made by the IRB.
• Because this tecovirimat EA-IND protocol is solely for treatment use, CDC determined that its use does not constitute research involving human subjects as defined by 45 CFR 46.102, therefore, the federal-wide assurance requirements do not apply.
• Facilities that have elected to rely on the CDC IRB for centralized review and approval: If you would like to terminate this reliance agreement, please submit a "Request Action for Closure" in REDCap using your own unique link, which was provided to you via email when the reliance agreement was executed. You may locate it by searching your email inbox for "Fully Executed Agreement to Rely on CDC IRB for Expanded Access IND for TPOXX." If you are unable to locate your own unique link, please contact huma@cdc.gov.