Efficacy and safety study of intravenous brincidofovir compared to intravenous cidofovir for the treatment of adenovirus infection in children and adults after stem cell transplant

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Symbio Pharmaceuticals Ltd.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

6 May 2026 → ongoing

Decision date (initial)

2025-10-03

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

SymBio Pharmaceuticals Limited

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess efficacy of intravenous (IV) brincidofovir (BCV), compared with IV cidofovir (CDV), in subjects after allo-HCT with adenovirus (AdV) viremia.

Secondary objectives 2

1. To assess the safety of IV BCV, compared with IV CDV, in subjects after allo HCT with AdV viremia.
2. To assess IV BCV pharmacokinetics (PK).

Conditions and MedDRA coding

Adenovirus viremia

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001904-PIP02-17

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Male and female, post-allo-HCT within last 180 days, aged 2 months and older at time of signing informed consent form.
2. Subject/Guardian willing and able to understand and provide written informed consent to participate in the study.
3. In the investigator’s judgement, the subject’s clinical condition justifies treatment with IV BCV or IV CDV for AdV infection.
4. Has adenoviremia
5. Men and women of childbearing potential (WOCBP) must be willing to use acceptable method(s) of contraception during the study and for at least 6 months after the last dose of IV BCV or at least 6 months after the last dose of IV CDV.
6. Women of childbearing potential (WOCBP) must agree to use two (2) acceptable forms of contraception (one of which must be a barrier method) during heterosexual intercourse. Males capable of fathering a child must agree to use acceptable method(s) of contraception during heterosexual intercourse.
7. Subject is non-pregnant, and either not breast feeding or willing to discontinue breast feeding prior to randomization.

Exclusion criteria 13

1. Subject received an allo-HCT with a matched sibling donor
2. Subject received more than 5 mg/kg of CDV for any reason in the 21 days prior to first dose of study drug.
3. Subject is allergic or hypersensitive to IV BCV or IV CDV or any of their components.
4. Subject received anti-AdV-specific cell-based therapy within 3 weeks prior to W1D1 or an anti-AdV vaccine at any time.
5. Subject has participated in any other investigational study within 30 days (or within 5.5 half-lives of the investigational product, whichever is longer) before signing the informed consent form (ICF), is currently participating in another interventional treatment trial with an investigational agent or is using an investigational device at the time of Screening.
6. Subject has NIH Stage 3 or higher acute GVHD of the gut within 7 days prior to W1D1.
7. Subject has NIH Stage 2 or higher acute GVHD of the liver within 7 days prior to W1D1 (i.e., bilirubin>3 mg/dL [International System, SI: >51 μmol/L]).
8. Subject has exclusionary hepatic parameters within 7 days prior to W1D1: • Total bilirubin >3 mg/dL (SI: >51 μmol/L) except for subjects with Gilbert’s Disease, • Prothrombin time-international normalized ratio (PT INR) >2x ULN, unless attributed to AdV. • ALT or AST >5x upper limit of normal (ULN), except if it is judged by the PI to be due to the AdV infection. Note: Subjects with elevated serum transaminases >5x ULN (CTCAE Grade 3 or higher) due to AdV will be required to demonstrate improvement and must stop study drug if the elevated values have not improved by W3D1: either at least one CTCAE grade or clinical improvement based on the physician’s assessment.
9. Subject has uncontrolled viral (other than AdV), bacterial, or fungal infection(s) leading to hemodynamic instability or radiologic or laboratory evidence attributable to worsening disease.
10. Subject has any other disease, or laboratory abnormality, or clinical finding that, in the judgment of the investigator, would put the subject at unacceptable risk for participation or interfere with study assessments or data quality.
11. Subject is expected to die from a non-adenovirus cause within 30 days from the date of ICF.
12. Subject is critically ill, for example with sepsis on high dose vasopressors and mechanical ventilation.
13. Subject is unable to comply with protocol visits and procedures.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of subjects with AdV virological success

Secondary endpoints 13

1. Proportion of subjects with overall success
2. Proportion of subjects with clinical success
3. Proportion of subjects with AdV virological success
4. Correlation of virologic success and clinical response
5. AdV-free survival
6. Time to AdV virological success
7. Rate of AdV recurrence
8. Length of hospitalization and length of ICU stay
9. Desirability Of Outcome Ranking (DOOR) Analysis for benefit-risk estimation
10. All-cause mortality
11. Adenovirus attributed mortality, as adjudicated by the EAC
12. Primary malignancy relapse-free survival
13. Incidence and severity of treatment-emergent adverse events (TEAEs)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Symbio Pharmaceuticals Ltd.

Sponsor organisation

Symbio Pharmaceuticals Ltd.

Address

4 1-28 Toranomon

City

Minato

Postcode

105-0001

Country

Japan

Scientific contact point

Organisation

Symbio Pharmaceuticals Ltd.

Contact name

Chief Medical Officer

Public contact point

Organisation

Symbio Pharmaceuticals Ltd.

Contact name

Chief Medical Officer

Third parties 8

Locations

4 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 33 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications