IV BCV for Adenovirus Infections

(ATHENA Trial)

Recruiting at 12 trial locations

Overseen By Rochelle Maher

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: SymBio Pharmaceuticals

Disqualifiers: Weight ≥120 kg, Grade 2+ diarrhea, Stage 4 skin GVHD, Stage 2+ liver GVHD, Stage 2+ gut GVHD

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 4 weeks

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called brincidofovir (BCV) to assess its safety and tolerability for people with adenovirus (AdV) or cytomegalovirus (CMV) infections. Participants will receive BCV through an IV in varying doses and schedules to determine the most effective method. The trial seeks individuals with significant AdV infection (high levels of the virus in the blood) or CMV who are also in a weakened immune state, making them more susceptible to these viruses. The trial aims to help these patients manage their viral infections more effectively. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinator or your doctor for guidance.

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

Research has shown that brincidofovir (BCV) is generally safe for people. In one study, patients with adenovirus infections took BCV and showed good tolerance, experiencing no serious side effects. Another study focused on children with adenovirus infections who had stem cell transplants; they also tolerated BCV well, with only a few mild or moderate side effects.

These studies suggest that BCV is usually safe for humans. However, like any medication, it can cause side effects. Prospective participants should discuss any concerns with healthcare providers before considering joining a trial. ^{1 2 3 4 5}

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

Brincidofovir is unique because it uses a novel approach to tackle adenovirus infections. Unlike the standard antiviral treatments, which often involve oral or topical medications, Brincidofovir is administered intravenously, allowing for a continuous and controlled delivery directly into the bloodstream. This method can enhance the drug's effectiveness by maintaining stable drug levels in the body. Additionally, Brincidofovir's mechanism targets viral DNA polymerase, which is different from many existing treatments, potentially offering a more potent and targeted antiviral action. Researchers are excited about its potential to treat adenovirus infections more effectively and with fewer side effects.

What evidence suggests that this trial's treatments could be effective for adenovirus infections?

Research has shown that brincidofovir (BCV) may help treat adenovirus (AdV) infections. In this trial, participants will receive different dosages of BCV to evaluate its effectiveness. Studies have found that BCV can lower AdV levels in the blood to undetectable levels in more than half of the patients. In some studies, up to 90% of patients eliminated the virus within four weeks of starting treatment. Importantly, these trials revealed no new safety concerns. This suggests that BCV could be a good option for managing AdV infections, especially in people with weakened immune systems. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals aged 2 months and older with Adenovirus infection, showing high virus levels in the blood. Participants must either have a widespread infection or be immunocompromised with asymptomatic or localized disease. They should need intravenous treatment but can't join if they have severe skin reactions, gut/liver issues from graft-versus-host disease, weigh over 120 kg, or had recent severe diarrhea.

Inclusion Criteria

AdV DNA viremia >10,000 copies/mL from a single sample, or 2 samples greater than 48 hours apart with the second result higher than the first and both greater than 1000 copies/mL, from the data obtained from the designated central virology laboratory of the local laboratory using the blood sample(s) collected informed consent has been obtained and within 7 days prior to Day 1 (AdV DNA viremia results collected within the 7 day window, but prior to consent may be used if the Informed Consent Form (ICF) signed by the subject provides approval).

Male or female, aged 2 months and older at the time of informed consent.

Either (a) have disseminated AdV disease or (b) have an underlying immunocompromised state, and have asymptomatic AdV infection or localized AdV disease.

Exclusion Criteria

NIH Stage 4 acute GVHD of the skin (i.e., generalized erythroderma with bullous formation) within 7 days prior to Day 1.

NIH Stage 2 or higher acute GVHD of the gut (i.e., diarrhea >556 mL/m2/day for pediatric subjects [or >1000 mL/day for young adults as applicable, at centers in the United States only], or severe abdominal pain with or without ileus) within 7 days prior to Day 1.

Subjects who weigh ≥120 kg.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous Brincidofovir (BCV) at varying doses for 4 weeks

4 weeks

8 visits (in-person) for BIW dosing, 4 visits (in-person) for QW dosing

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 weeks

Weekly monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Brincidofovir

Trial Overview The study tests different doses of an intravenous drug called Brincidofovir (BCV) to find a safe and tolerable amount for treating Adenovirus infections. It's given in increasing amounts to see how patients handle it.

How Is the Trial Designed?

Group I: BCV 0.4 mg/kg QW Experimental Treatment 1 Intervention

BCV: 0.4 mg/kg administered as a continuous IV infusion over 2 hours

Group II: BCV 0.4 mg/kg BIW Experimental Treatment 1 Intervention

BCV: 0.4 mg/kg administered as a continuous IV infusion over 2 hours

Group III: BCV 0.3mg/kg BIW Experimental Treatment 1 Intervention

BCV: 0.3 mg/kg administered as a continuous IV infusion over 2 hours

Group IV: BCV 0.2mg/kg BIW Experimental Treatment 1 Intervention

BCV: 0.2 mg/kg administered as a continuous IV infusion over 2 hours

Brincidofovir is already approved in United States for the following indications:

Approved in United States as Tembexa for:

• Smallpox disease caused by variola virus

Who Is Running the Clinical Trial?

SymBio Pharmaceuticals

Lead Sponsor

Trials

24

Recruited

740+

Founded

2005

Headquarters

Tokyo, Japan

Known For

Rare disease research

Top Products

brincidofovir, bendamustine liquid formulation, rigosertib sodium

Published Research Related to This Trial

Brincidofovir (CMX001) is an effective oral treatment for severe adenoviral pneumonia in renal transplant recipients, especially when intravenous cidofovir causes renal insufficiency.

Brincidofovir has advantages over cidofovir, including better oral bioavailability, no nephrotoxicity, and higher levels of the active drug, making it a safer option for treating adenovirus infections in transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brincidofovir (CMX001) for the Treatment of Severe Adenoviral Pneumonia in Kidney Transplant Recipient. Sudhindra, P., Knoll, B., Nog, R., et al.[2020]

Brincidofovir, a new oral treatment for adenovirus infections, shows promise in being safe and effective in reducing adenovirus levels and related complications in immunosuppressed patients, particularly those undergoing hematopoietic stem cell transplants, as indicated by preliminary results from a phase III clinical trial.

Unlike its predecessor cidofovir, brincidofovir has better cellular uptake and does not cause kidney damage, making it a significant advancement in the treatment of adenovirus infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New drug on the horizon for treating adenovirus. Wold, WS., Toth, K.[2020]

Brincidofovir (BCV) has shown promise as a treatment for disseminated adenovirus infections (d-ADV) in pediatric patients after hematopoietic cell transplant (HCT), which are often fatal and have limited treatment options.

In a report involving four pediatric HCT recipients, all were successfully treated with BCV, indicating its potential efficacy in managing this serious infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid Virologic Response to Brincidofovir in Children with Disseminated Adenovirus Infection. Chan, SY., Prockop, SE., Boulad, F., et al.[2021]

In a study of 8 pediatric HSCT recipients with refractory adenovirus infections, 75% experienced complete resolution of AdV DNAemia and intestinal infections after treatment with brincidofovir (BCV).

High levels of AdV DNAemia (over 1 × 10^9/mL) and poor lymphocyte recovery were linked to increased mortality, but early AdV DNAemia did not worsen outcomes, indicating that BCV may be a promising option for managing AdV infections in immunocompromised patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Brincidofovir in Pediatric Stem Cell Transplant Recipients With Adenovirus Infections. Ehlert, K., Schulte, JH., Kühl, JS., et al.[2021]

Brincidofovir (BCV) demonstrated effective anti-adenoviral activity in five pediatric patients with adenovirus infections following hematopoietic stem cell transplantation, showing a good safety profile without nephrotoxicity.

All patients treated with BCV responded well, with a median time of 30 days to achieve negative adenoviremia, suggesting BCV could be a valuable option for preemptive therapy in this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brincidofovir as a Salvage Therapy in Controlling Adenoviremia in Pediatric Recipients of Hematopoietic Stem Cell Transplant. Meena, JP., Phillips, RS., Kinsey, S.[2023]

Brincidofovir (BCV) was successfully used to treat a 9-year-old girl with disseminated adenovirus infection after hematopoietic stem cell transplantation, demonstrating its potential as an effective antiviral therapy in immunocompromised patients.

Compared to standard antiviral treatments like Cidofovir, Brincidofovir offers increased efficacy against various viral infections, has a better safety profile with limited toxicity, and can be administered orally, making it more accessible in different healthcare settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Adenovirus Infection with Brincidofovir in an Immunocompromised Patient after Hematological Stem Cell Transplantation. Van Genechten, T., van Heerden, J., Bauters, T., et al.[2020]

CMX001 (Brincidofovir) is an orally bioavailable antiviral that is converted inside cells to its active form, cidofovir diphosphate, enhancing its effectiveness against double-stranded DNA viruses.

The lipid conjugation of CMX001 allows for higher concentrations of the active drug within cells while maintaining lower levels in the bloodstream, which may improve safety and reduce potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of CMX001 (Brincidofovir) for the treatment of serious diseases or conditions caused by dsDNA viruses. Florescu, DF., Keck, MA.[2022]

Brincidofovir (BCV) demonstrated antiviral activity against adenoviruses in immunocompromised patients, with 67% of subjects on the BCV twice weekly regimen achieving undetectable adenovirus viremia after one week, compared to only 29% in the once weekly group and 33% in the placebo group.

While BCV treatment showed a trend towards lower all-cause mortality compared to placebo, it was associated with a higher incidence of diarrhea and acute graft-versus-host disease, indicating the need for careful monitoring of side effects in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brincidofovir for Asymptomatic Adenovirus Viremia in Pediatric and Adult Allogeneic Hematopoietic Cell Transplant Recipients: A Randomized Placebo-Controlled Phase II Trial. Grimley, MS., Chemaly, RF., Englund, JA., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3608125/

Safety and Efficacy of CMX001 as Salvage Therapy for Severe ... We retrospectively analyzed 13 patients with adenovirus disease and viremia treated with CMX001; data were available for ≥4 weeks after initiation of CMX001 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02087306

NCT02087306 | Study to Assess the Safety and Efficacy of ... The primary efficacy endpoint was the evaluation of the effect of brincidofovir (BCV) on all-cause mortality when used for the treatment of disseminated ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723018791

Preliminary Results of a Phase 2a Clinical Trial to Evaluate ... Adenovirus (AdV) may cause fatal infections in immunosuppressed patients including recipients of allogeneic hematopoietic cell transplant. Brincidofovir (BCV) ...

4. astctjournal.org astctjournal.org/article/S1083-8791(14)00844-1/fulltext

Preliminary Results from the AdVise Study Evaluating ... AdV viremia was suppressed to undetectable in over half of enrolled subjects. No new safety concerns were identified in this complex patient population. These ...

5. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/112/500106/Preliminary-Results-of-a-Phase-2a-Clinical-Trial

Preliminary Results of a Phase 2a Clinical Trial to Evaluate ... In Cohort 3, it is notable that 90 % of patients achieved AdV viremia clearance in ≤ 4 weeks of treatment with BCV IV. In Cohorts 2 and 3, all ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/21963623/

Safety and efficacy of CMX001 as salvage therapy ... - PubMed We retrospectively analyzed 13 patients with adenovirus disease and viremia treated with CMX001; data were available for ≥ 4 weeks after initiation of CMX001 ...

7. nature.com nature.com/articles/s41409-021-01285-y

Safety and efficacy of brincidofovir for Adenovirus infection ... Safety and efficacy of brincidofovir for Adenovirus infection in children receiving allogeneic stem cell transplantation: an AIEOP retrospective analyses