Brincidofovir vs Cidofovir for Adenovirus Infections

(ENOVIA Trial)

Not yet recruiting at 60 trial locations

Overseen By Rochelle Maher

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: SymBio Pharmaceuticals

Disqualifiers: Matched sibling donor, Anti-AdV therapy, others

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

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

Compensation: Varies

Number of Visits: 12

Duration: Up to 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines two treatments, brincidofovir and cidofovir, to determine which is more effective for individuals who have undergone a stem cell transplant and now have adenovirus in their blood. Adenovirus can be serious for those with weakened immune systems, such as post-transplant patients. The study will compare the effectiveness of each drug in eliminating the virus over a period of up to 12 weeks. Individuals who have had a stem cell transplant in the last six months and have adenovirus in their blood may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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

Research has shown that brincidofovir (BCV) is generally safe and well-tolerated. Previous studies found that BCV effectively reduced adenovirus (AdV) levels in the blood without introducing new safety concerns. In one study, no serious new safety issues appeared in patients, even those with complex health conditions. Some possible side effects, such as stomach problems, were noted but were uncommon.

In contrast, cidofovir (CDV) has been used to treat viral infections but carries some risks. CDV can cause serious side effects, including kidney damage, so patients often require close monitoring during its use.

Both BCV and CDV have effectively lowered virus levels. However, BCV appears to have a better safety profile, with fewer serious side effects reported compared to CDV. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Brincidofovir for adenovirus infections because, unlike traditional treatments like Cidofovir, it offers the potential for oral administration, making it more convenient for patients. Brincidofovir is a lipid conjugate of Cidofovir, which means it might have a better safety profile, potentially reducing kidney toxicity commonly associated with Cidofovir. Additionally, Brincidofovir's mechanism allows it to be more effectively absorbed and utilized in the body, possibly leading to improved outcomes for those affected by adenovirus infections.

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

This trial will compare Brincidofovir (BCV) and Cidofovir (CDV) for treating adenovirus (AdV) infections. Research has shown that Brincidofovir may be effective. Specifically, one study indicated that almost two-thirds of patients who received BCV experienced a significant decrease in virus levels after just one week. Another study found that 90% of patients eliminated the virus from their blood within four weeks, with no return of the virus. Cidofovir, a well-known antiviral, has been effective in the past and is another treatment option in this trial. However, researchers are investigating BCV as a potentially better option with fewer side effects. These findings suggest that BCV could be a strong choice for removing AdV from the body. ^{1 2 3 6 7}

Who Is on the Research Team?

Nkechi Azie

Principal Investigator

SymBio Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for both adults and children who have received an allogeneic hematopoietic cell transplant (allo-HCT) and are now experiencing adenovirus infections. Participants must show evidence of the virus in their blood but specific inclusion and exclusion criteria details were not provided.

Inclusion Criteria

Has adenoviremia with criteria including AdV viremia DNA levels and specific lymphocyte count or transplant history

Subject/Guardian willing and able to understand and provide written informed consent to participate in the study

My doctor thinks IV treatment is necessary for my AdV infection.

Exclusion Criteria

Subject is allergic or hypersensitive to IV BCV or IV CDV or any of their components

I received a stem cell transplant from a sibling who was a match.

Subject has participated in any other investigational study within 30 days before signing the informed consent form (ICF) or is currently participating in another interventional treatment trial with an investigational agent or using an investigational device at the time of Screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either IV BCV or IV CDV until AdV viremia is undetectable or for a maximum of 12 weeks

Up to 12 weeks

Weekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Visits at Week 12 and Week 24

What Are the Treatments Tested in This Trial?

Interventions

• Brincidofovir
• Cidofovir

Trial Overview

The study compares two antiviral drugs, IV Brincidofovir (BCV) and IV Cidofovir (CDV), to see which is better at treating adenovirus infections post-allo-HCT. Patients will receive treatment until the virus can't be detected or up to 12 weeks, with follow-ups extending to 24 weeks after starting treatment.

How Is the Trial Designed?

Group I: IV BCV Experimental Treatment 1 Intervention

Group II: IV CDV Active Control 1 Intervention

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

Citations

1.

pmc.ncbi.nlm.nih.gov

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

Safety and Efficacy of CMX001 as Salvage Therapy for Severe ...

Nearly two-thirds of patients treated with CMX001 had a ≥10-fold drop in VL after just 1 week of therapy, and up to 70% patients by 2 months of treatment.

2.

astctjournal.org

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

Preliminary Results from the AdVise Study Evaluating ...

In subjects with positive qualitative AdV PCR at BL, 42% (5/12) cleared AdV in respiratory secretions, 33% (5/15) in urine and 27% (4/15) in stool. Six of the ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S2666636723018791

Preliminary Results of a Phase 2a Clinical Trial to Evaluate ...

In C3, it is notable that 90 % of patients achieved AdV viremia clearance in ≤ 4 weeks of treatment. In C2 and C3, no recurrence of viremia occurred through the ...

4.

symbiopharma.com

symbiopharma.com/en/news/pdf/20241023e.pdf

SymBio presents data from Phase IIa clinical trial showing ...

In Cohort 3 (IV BCV 0.4 mg/kg),. 9 cases (100%) showed not only elimination of AdV from blood, but also disappearance or improvement of AdV.

5.

academic.oup.com

academic.oup.com/ofid/article/12/Supplement_1/ofae631.310/7987268

P-103. Adenoviremia Clearance Following Treatment with ...

Athena is a multiple ascending dose study of the safety and efficacy of IV BCV in treatment of serious AdV infection. NCT04706923. graphic.

6.

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 ...

Conclusions: BCV IV was found to be safe and well tolerated in immunocompromised patients. Notably, the potentially serious gastrointestinal and ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02087306

Study to Assess the Safety and Efficacy of Brincidofovir in ...

This was a Phase 3 open-label, non-randomized, multicenter study of the safety, tolerability, and efficacy of oral brincidofovir (BCV) when administered twice ...