Tecovirimat (TPOXX) for Treatment of Mpox

Oral Tecovirimat Access through the NIH STOMP Trial

Oral tecovirimat for treatment of mpox is primarily available through enrollment in the Study of Tecovirimat for Mpox (STOMP). Researchers and clinicians do not know whether tecovirimat is effective or how safe it is in treating mpox. The STOMP trial is designed to collect data to help answer these scientific questions.

• Providers are encouraged to inform patients with mpox about STOMP and to recommend they consider seeking enrollment in STOMP. The study has randomized and open-label treatment arms, and remote enrollment is available Monday through Friday.
• Patients do not have to have severe disease or be at high risk of severe disease to enroll in the study. Non-pregnant or non-breastfeeding adults with mild illness who do not have severe immunocompromise or active skin conditions are enrolled in STOMP’s placebo-controlled, randomized arm.
• Two-thirds of patients in the randomized arm receive tecovirimat. If the participants in the randomized arm develop severe disease or have persistent severe pain, they are switched to the open-label arm.
• The patients who meet the eligibility criteria to receive tecovirimat for treatment of mpox under CDC’s EA-IND protocol can also receive oral tecovirimat through STOMP. They get enrolled in the open-label arm of the STOMP study, where they are guaranteed tecovirimat treatment.
• Participants in both arms of STOMP will be followed for at least 57 days and will be asked to fill out a symptom diary, do daily skin checks at home, and attend virtual and in-person clinic appointments, where they will undergo physical exams and provide blood and other specimens, including fluid from their lesions or eye if ocular infection is involved. For participants who are enrolled remotely, telehealth visits will be conducted.
• For more information and to be connected with a STOMP study site, the STOMP call center can be reached at (855) 876-9997 from 9 a.m. to 10 p.m. Monday through Friday; on Saturday from 9 a.m. to 4 p.m.; and on Sunday from 1 to 6 p.m. U.S. Eastern time. The STOMP team recommends contacting the call center and not to directly contact the participating study sites in order to be directed to the site that can provide the quickest help.

Providers with patients who are ineligible for STOMP’s open-label arm (e.g., illness ≥ 14 days or prior TPOXX receipt) but meet EA-IND eligibility for tecovirimat treatment for mpox should contact their state, local, or territorial health departments to see if any oral TPOXX remains available within their jurisdiction from prior prepositioned supply. While the large-scale prepositioning of stockpiled oral tecovirimat stopped on February 27, 2023, by ASPR, some of the deployed supply still remains within expiry.  Any remaining supply can be used for EA-IND eligible patients. If there is no local supply, state, local, or territorial health departments should request oral TPOXX on providers’ behalf by calling the CDC Emergency Operations Center (EOC) at (770) 488-7100 (24×7) or poxvirus@cdc.gov. (This email box is monitored from 9 a.m. to 4 p.m. U.S. Eastern time on non-holiday weekdays).

For patients who require intravenous TPOXX treatment and meet treatment eligibility under the EA-IND protocol, providers, in conjunction with jurisdictional health departments, can contact the CDC EOC or e-mail poxvirus@cdc.gov to make the request; a clinical consultation with a CDC clinical duty officer regarding management of hospitalized patients can also be requested.

Tecovirimat Expanded Access IND Information

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. Use of tecovirimat under this EA-IND protocol is for patients with laboratory-confirmed or suspected mpox who meet the eligibility criteria as outlined in Section 2.0 of the protocol [494 KB, 28 pages]. 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

• • These patients might be at high risk for protracted or life-threatening manifestations of mpox based on prior experience from other orthopoxvirus infections in humans.

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

• • 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.

Patients with mpox who meet the above-mentioned EA-IND eligibility for tecovirimat treatment may also be eligible for oral tecovirimat through the open-label tecovirimat arm of NIH’s STOMP study.

The EA-IND eligibility criteria are closely aligned with the STOMP open-label arm’s eligibility criteria regarding those with severe immunocompromise, people who are pregnant or lactating, and children. However, the definition of protracted or life-threatening manifestations of mpox listed above for tecovirimat treatment under the EA-IND protocol are narrower than STOMP’s definition of severe disease.

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 [521 KB, 8.5″ x 11″] for an overview of the tecovirimat IND online registry process.

• Through the registry, providers can submit
  • Form FDA 1572
  • Patient Intake Form
  • Clinical Outcome Form
• Any questions about the registry and accessing electronic tecovirimat IND Patient Intake and Clinical Outcome forms can be directed to regaffairs@cdc.gov.

Tecovirimat EA-IND Protocol

• • The current EA-IND protocol  [494 KB, 28 pages] is version 6.4 updated June 5, 2024.
  • On June 5, 2024, the CDC IRB approved [372 KB, 2 pages] a protocol amendment (version 6.4 updated June 5, 2024). An updated CDC IRB memo approving continuation of the protocol will be posted prior to the current expiry of July 23, 2024.
  • 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  [855 KB, 2 pages] (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

1. Informed Consent Form (version 6.4 dated June 5, 2024): English [249 KB, 7 pages] | Spanish [196 KB, 8 pages] Obtain prior to treatment.
   1. Alternative Consent Forms that can be used to obtain informed consent:
      • Short Form (English) [155 KB, 3 pages] | Spanish [140 KB, 4 pages]
      • Written Summary (English) [204 KB, 6 pages] | Spanish [172 KB, 7 pages]
   2. 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.
   3. Patient Intake Form (version 6.4 dated June 5, 2024): Baseline assessment. Access the electronic form through the Tecovirimat IND Online Registry.
   4. 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.
   5. Serious Adverse Events: Per FDA requirement, report life-threatening or serious adverse events associated with tecovirimat by completing a PDF MedWatch Form [956 KB, 5 pages] 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 [220 KB, 2 pages] (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 [375 KB, 4 pages] (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) [4 MB, 2 pages], 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.