Tecovirimat for Monkeypox

(PLATINUM-CAN Trial)

Not currently recruiting at 2 trial locations

Overseen By Hansi Peiris

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Marina Klein

Must not be taking: Tecovirimat

Disqualifiers: Weight < 40 kg, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medication, Tecovirimat, to determine its effectiveness for people with monkeypox who aren't hospitalized. Researchers aim to assess how well Tecovirimat works and its safety in treating monkeypox, a virus causing skin and mucosal sores. Participants will receive either Tecovirimat or a placebo (a pill with no medicine) to compare effects. Suitable candidates for this trial have a confirmed or suspected monkeypox infection with skin or mucosal sores and do not require hospitalization. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are currently using tecovirimat, you cannot participate in the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tecovirimat, the treatment under study, has undergone trials to assess its efficacy and safety for treating monkeypox. Some animal studies have indicated its potential benefits, but information about its safety for people with monkeypox remains limited. Reports from other uses of tecovirimat suggest that serious side effects are rare, but data is insufficient to fully understand its safety in humans with monkeypox. As this study is in a later phase, there is some confidence in its safety, but more solid evidence is needed for certainty. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for monkeypox?

Unlike standard treatments for monkeypox, which primarily focus on managing symptoms, Tecovirimat targets the virus itself. Tecovirimat works by inhibiting a viral protein essential for the virus's replication, which may reduce the duration and severity of the infection. Researchers are excited about this treatment because it represents a more direct approach to tackling monkeypox, potentially leading to quicker recovery times and reduced transmission.

What evidence suggests that Tecovirimat might be an effective treatment for monkeypox?

Research shows that tecovirimat, which participants in this trial may receive, may help treat monkeypox. Early studies found that people taking tecovirimat healed faster from skin sores and had less virus in their bodies. The treatment appears safe, with few side effects reported. Another study noted that skin issues cleared up quickly with tecovirimat. These results suggest that tecovirimat could be a good option for treating monkeypox. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 years old, weighing at least 40 kg, with confirmed or suspected monkeypox infection based on PCR tests or visible symptoms. Participants should have had sexual contact within the last 21 days or exposure to someone with monkeypox and must be able to manage their condition without hospitalization.

Inclusion Criteria

I've had sexual contact recently and have skin or mucosal lesions.

I can be treated without needing to stay in the hospital.

The participant (or legally acceptable representative) has provided documented informed consent and comply to the require procedures for the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial visit for screening and sample collection

Treatment

Participants receive Tecovirimat or placebo for 14 days

2 weeks

Self-assessment diaries and self-testing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Weekly self-reports and potential in-person visits

Extension/Long-term follow-up

Participants may continue to be monitored for long-term outcomes and safety

Up to 4 months

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Tecovirimat

Trial Overview The PLATINUM-CAN trial is testing Tecovirimat against a placebo in non-hospitalized patients with monkeypox. It's randomized, meaning people are put into the Tecovirimat or placebo group by chance, and aims to find out how effective and safe Tecovirimat is for treating monkeypox outside of hospitals.

How Is the Trial Designed?

Group I: Tecovirimat Experimental Treatment 1 Intervention

Tecovirimat (TPOXX®) Capsules, 200 mg (as tecovirimat monohydrate) administered as 600 mg (three 200 mg capsules) taken twice daily orally, every 12 hours, within 30 minutes after a full meal of moderate or high fat (approximately 25 g of fat) for 14 days

Group II: Placebo Placebo Group 1 Intervention

Identical placebo supplied by SIGA Technologies Inc.

Tecovirimat is already approved in United States, European Union, Canada for the following indications:

Approved in United States as TPOXX for:

• Smallpox
• Monkeypox
• Cowpox

Approved in European Union as TPOXX for:

• Smallpox
• Monkeypox
• Cowpox

Approved in Canada as TPOXX for:

• Smallpox
• Monkeypox
• Cowpox

Who Is Running the Clinical Trial?

Marina Klein

Lead Sponsor

Trials

2

Recruited

200+

University of British Columbia

Collaborator

Trials

1,506

Recruited

2,528,000+

Unity Health Toronto

Collaborator

Trials

572

Recruited

470,000+

CIHR Canadian HIV Trials Network

Collaborator

Trials

41

Recruited

6,400+

University Health Network, Toronto

Collaborator

Trials

1,555

Recruited

526,000+

McGill University Health Centre/Research Institute of the McGill University Health Centre

Collaborator

Trials

476

Recruited

170,000+

Published Research Related to This Trial

Vaxigrip Tetra®, a new quadrivalent influenza vaccine, has been shown to have a similar safety profile and immunogenicity to the licensed trivalent influenza vaccine (TIV), based on data from seven phase III clinical trials.

The new vaccine effectively enhances immune response against an additional B strain without compromising the response to the other three strains, making it suitable for individuals aged 6 months and older, including young children and older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and Safety of the New Inactivated Quadrivalent Influenza Vaccine Vaxigrip Tetra: Preliminary Results in Children ≥6 Months and Older Adults. Montomoli, E., Torelli, A., Manini, I., et al.[2022]

The antiviral drug tecovirimat (TPOXX) has shown strong efficacy against the monkeypox virus (MPXV), preventing its replication in laboratory tests and significantly reducing viral levels in infected mice.

In a mouse model using a Canadian isolate of MPXV, daily oral treatment with TPOXX led to marked reductions in viral titers, suggesting it could be a key treatment option for managing the current outbreak.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo efficacy of tecovirimat against a recently emerged 2022 monkeypox virus isolate. Warner, BM., Klassen, L., Sloan, A., et al.[2023]

Tecovirimat (ST-246) has been shown to be effective against the monkeypox virus (MPXV) isolate from the first clinical case in France, requiring only nanomolar concentrations for efficacy, which is significantly lower than the micromolar concentrations needed for cidofovir.

These findings support the ongoing use of tecovirimat in human clinical trials for treating monkeypox, highlighting its potential as a preferred treatment option during the current outbreak.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tecovirimat is effective against human monkeypox virus in vitro at nanomolar concentrations. Frenois-Veyrat, G., Gallardo, F., Gorgé, O., et al.[2023]

A total of 228 adverse drug reaction reports were analyzed for nirmatrelvir/ritonavir (Paxlovid®) in France, with serious reports making up 40% of the cases, highlighting the importance of monitoring its safety profile, especially in older patients (mean age 66).

Drug-drug interactions (DDIs) were a significant concern, accounting for over 13% of reports, primarily involving immunosuppressive drugs, and the main unexpected adverse reactions included high blood pressure, confusion, acute kidney injuries, and skin reactions, necessitating careful management in patients on multiple medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nirmatrelvir/ritonavir (Paxlovid®): French pharmacovigilance survey 2022. Bihan, K., Lipszyc, L., Lemaitre, F., et al.[2023]

During the 2022 monkeypox outbreak, tecovirimat was used extensively, and genomic sequencing revealed that while 96 out of 124 viral isolates from patients showed resistance, this was primarily in severely immunocompromised individuals receiving multiple treatments.

The overall frequency of resistant monkeypox viruses was low, at less than 1%, indicating that tecovirimat remains an effective treatment option for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tecovirimat Resistance in Mpox Patients, United States, 2022-2023. Smith, TG., Gigante, CM., Wynn, NT., et al.[2023]

In a double-blind trial involving 105 patients with dermatomycosis, 1% Ciclopirox solution demonstrated a significantly higher cure rate compared to placebo, indicating its efficacy as a topical antifungal treatment.

Ciclopirox was effective against several fungal species, including Trichophyton rubrum, T. violaceum, T. mentagrophytes, and Malassezia furfur, showcasing its broad-spectrum antifungal action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ciclopirox: a new topical pyrodonium antimycotic agent. A double-blind study in superficial dermatomycoses. Sehgal, VN.[2019]

This study will evaluate the efficacy and safety of oral tecovirimat in treating monkeypox and smallpox, involving 50 patients and focusing on the percentage of patients achieving negative PCR results for skin lesions after 14 days of treatment.

Participants will choose between receiving tecovirimat plus supportive treatment or only supportive treatment, with the study covering costs to ensure accessibility, highlighting a commitment to ethical research practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol of Tecopox study: a multicentre, open-label, double-arm trial to evaluate the efficacy and safety of oral tecovirimat therapy for patients with smallpox or monkeypox. Suzuki, T., Saito, S., Tsuzuki, S., et al.[2023]

Itraconazole was effective in treating P. marneffei infection in a study of 10 patients, with clinical improvement seen in 8 patients and a mean time to culture negativity of 57 days.

However, relapse of the infection occurred in 5 patients within four months after treatment, suggesting that long-term suppressive therapy may be necessary to prevent recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An efficacy study of itraconazole in the treatment of Penicillium marneffei infection. Supparatpinyo, K., Chiewchanvit, S., Hirunsri, P., et al.[2013]

A systematic review of antiemetic agents for preventing chemotherapy-induced nausea and vomiting (CINV) in children found that these medications, including aprepitant and ondansetron, are generally safe with manageable adverse effects.

While the recommended antiemetics are effective, it is important to consider individual patient risk factors, particularly for rare side effects like cardiac arrhythmia, and further research is needed to assess their long-term safety in pediatric cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of clinical practice guideline-recommended antiemetic agents for the prevention of acute chemotherapy-induced nausea and vomiting in pediatric patients: a systematic review and meta-analysis. Patel, P., Paw Cho Sing, E., Dupuis, LL.[2019]

Tecovirimat (TPOXX®) is an antiviral drug specifically designed to target orthopoxviruses, including the variola virus that causes smallpox, by inhibiting a key protein necessary for the virus's spread within the host.

Approved in July 2018 for treating smallpox in patients weighing 13 kg or more, tecovirimat's efficacy was demonstrated through animal studies, allowing it to gain approval under the FDA's Animal Rule.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tecovirimat: First Global Approval. Hoy, SM.[2022]

Statins, particularly simvastatin and atorvastatin, demonstrate significant antifungal activity against the Sporothrix schenckii complex, with minimum inhibitory concentrations (MICs) ranging from 8 to 512 μg/ml for different fungal forms.

The study indicates that statins can effectively inhibit mature biofilms of S. schenckii, suggesting their potential as a therapeutic option in treating sporotrichosis, especially when combined with classical antifungals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro inhibitory effect of statins on planktonic cells and biofilms of the Sporothrix schenckii species complex. Brilhante, RSN., Fonseca, XMQC., Pereira, VS., et al.[2020]

In a study of 74 HIV-infected patients with disseminated Penicillium marneffei infection, a treatment regimen of amphotericin B followed by itraconazole resulted in a 97.3% response rate, indicating high efficacy.

The treatment was found to be safe, with no serious adverse drug effects reported, suggesting it is a viable option for managing this infection in HIV patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amphotericin B and itraconazole for treatment of disseminated Penicillium marneffei infection in human immunodeficiency virus-infected patients. Sirisanthana, T., Supparatpinyo, K., Perriens, J., et al.[2022]

A 47-year-old woman developed muscle pain and elevated creatine kinase levels after taking high-dose simvastatin and itraconazole, leading to a diagnosis of statin-associated rhabdomyolysis, likely due to a drug interaction.

To prevent similar cases, it is recommended to use topical antifungals, non-CYP3A4-inhibiting antifungals like terbinafine, or temporarily stop statin treatment when antifungal therapy is needed for patients on statins metabolized by CYP3A4.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin-associated rhabdomyolysis triggered by drug-drug interaction with itraconazole. Dybro, AM., Damkier, P., Rasmussen, TB., et al.[2022]

HTX-019, a new injectable formulation of aprepitant, has shown a tolerable safety profile in cancer patients when administered via both a 30-minute IV infusion and a 2-minute IV injection, with no treatment-emergent adverse events occurring within 30 minutes of administration.

In a study of 135 patients undergoing chemotherapy, both administration methods were well tolerated, and while some adverse events were reported during chemotherapy, none were directly related to HTX-019, indicating its potential as a safe option for preventing chemotherapy-induced nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crossover safety study of aprepitant: 2-min injection vs 30-min infusion in cancer patients receiving emetogenic chemotherapy. Navari, RM., Mosier, MC.[2020]

Aprepitant is an effective antiemetic for preventing post-operative nausea and vomiting (PONV), showing superior efficacy in reducing vomiting with a long half-life and a favorable side effect profile.

The recent approval of an intravenous formulation of aprepitant may improve its convenience in clinical settings, although its higher cost compared to other antiemetics and lack of cost-effectiveness studies remain concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pharmacological overview of aprepitant for the prevention of postoperative nausea and vomiting. Padilla, A., Habib, AS.[2023]

Citations

1. cdc.gov cdc.gov/monkeypox/hcp/clinical-care/tecovirimat.html

Tecovirimat (TPOXX) for Treatment of Monkeypox 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10389504/

Efficacy of smallpox approved tecovirimat (Tpoxx) drug ... The skin imperfections immediately disappeared, and the results revealed no significant negative effects9. Another report documented mild ...

3. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2400189

Tecovirimat Use under Expanded Access to Treat Mpox in the ... Multiple clinical trials are underway to evaluate the effectiveness of tecovirimat; preliminary data from one of the studies (PALM007) was ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/jmv.70122

Effectiveness of Tecovirimat in Mpox Cases: A Systematic ... Some studies report promising results regarding symptom resolution, lesion healing, and the reduction of viral load, particularly when ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05597735

Study Details | NCT05597735 | Assessment of the Efficacy ... This study aims to evaluate whether tecovirimat is an efficient and safe antiviral in the treatment of monkeypox in adults and adolescents (14 years old and ...

6. cdc.gov cdc.gov/mmwr/volumes/71/wr/mm7137e1.htm

Clinical Use of Tecovirimat (Tpoxx) for Treatment ... ... data obtained from animal models; there are no safety or efficacy data regarding its use in patients with Monkeypox virus infection. What is ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9765296/

Tecovirimat for Treatment of Human Monkeypox Virus - PMC Therefore, all dosing recommendations for children are based on pharmacokinetic simulations, and no safety data exist. Recommended dosing is ...