Study of DAA Treatment for Children and Adolescents With Active HCV Infection in Cambodia

HCV Infection Clinical Trial

— HEPEDIAC  

Official title:

Pilot Therapeutic Study of DAA Treatment for Children and Adolescents With Active HCV Infection in Cambodia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05992077
• Other study ID #: ANRS 12420 HEPEDIAC
• Status: Recruiting
• Phase: N/A
• Start date: August 7, 2023
• Est. completion date: June 2025

Study information

• Verified date: March 2024
• Source: ANRS, Emerging Infectious Diseases
• Contact: Fatoumata Coulibaly
• Phone: 0144236110
• Email: fatoumata.coulibaly[@]anrs.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to evaluate the effectiveness of sofosbuvir/daclatasvir combination for children aged ≥ 6 years old and adolescents with active HCV infection in Cambodia

Description:

Non-comparative multicenter pilot therapeutic prospective study conducted in Phnom Penh and Siem Reap and divided in 2 phases:

Screening phase:

First, all children aged more than 6 years old and adolescents under 18 years old will be screened for HCV infection using Bioline HCV rapid test in two paediatric populations in Phnom Penh and Siem Reap: 1/ children born from HIV/HCV co-infected women followed in OI/ART sites 2/ children hospitalized in paediatric department of Kantha Bopha Foundation Children's Hospitals and of the National Pediatric Hospital.

HCV RNA will be performed in case of HCV rapid test positivity. A case-control study will be performed to evaluate the risk factors associated to HCV acquisition. Cases will be defined as children with positive HCV RDT and controls as children with negative HCV RDT. Four controls will be randomly selected for one case.

Therapeutic phase:

Children and adolescents confirmed with active HCV infection (positive HCV RNA) during the first phase will be referred to a specific consultation in Kantha Bopha hospital or National Pediatric Hospital for treatment after evaluation of liver disease. Patients with a weight > 25 kg will be treated with a sofosbuvir/daclatasvir combination for 12 weeks with adult dose (400/60 mg), children with a weight between 14 and 25 kg will be treated with the same sofosbuvir/daclatasvir combination with the half adult dose (200/30 mg) for 12 weeks. For all children and adolescents, residual plasma concentrations (trough concentrations) of the drugs will be assessed after 2 weeks of treatment. For the first 20 children and adolescents included (10 children weighing between 14 and 25 kg and 10 weighing more than 25 kg), whatever their HIV status and ARV treatment, a complete pharmacokinetic analysis will be performed prior to drug administration and +1h, +2h, +6h and +10h after drugs intake. A non-compartimental analysis using Phoenix WinNonlin 8.1 (Certara, Princeton, NJ, USA) will be performed to estimate the pharmacokinetic parameters of sofosbuvir, GS-331007 and daclatasvir. Maximal concentration (Cmax), trough concentration at steady state (Ct), minimal concentration (Cmin) and the time required to reach Cmax (Tmax) are the observed parameters. The area under the curve (AUCtau) will be estimated by the linear up log down trapezoidal method using the predose concentration as 24-hour postdose concentrations.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 21000
• Est. completion date: June 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

Inclusion Criteria:

Screening phase Inclusion criteria

• Aged = 6 years old with weight = 14 kg

• Aged <18 years old

• Hospitalized in one of the 3 paediatric departments of Kantha Bopha hospitals in Phnom Penh, Jayavarman VII hospital in Siem Reap OR in the pediatric department of the National Pediatric hospital OR born from HIV/HCV co-infected women followed in OI/ART sites in Phnom Penh

• Informed consent obtained with information sheet given and explained before the inclusion visit, the consent form signed by at least one of the 2 parents or legal guardians and oral assent collected if the child = 13 years old, at the latest the day of the inclusion

Non-inclusion criteria

• Any medical condition requiring intensive care and/or acute surgery

Therapeutic phase Inclusion criteria

• Aged = 6 years old with weight = 14 kg

• Aged < 18 years old

• HCV RNA detectable

• HCV treatment naive

• In case of HIV coinfection,

• HIV-1 infection confirmed according to Cambodian screening policies

• On ART for more than 6 months

• CD4 cell-count> 100 cells/µL and > 15% and HIV viral load < 1000 copies/mL at inclusion visit

• Informed consent obtained with information sheet given and explained before the inclusion visit and the consent form signed by at least one of the 2 parents and oral assent collected if the child = 13 years old, before any sample or drug administration corresponding to the therapeutic phase.

Non-inclusion Criteria:

• Suspicion of evidence of hepato-cellular carcinoma (HCC) or any other neoplasia

• Decompensated cirrhosis

• Co-infection with HBV (positive HBsAg)

• Advanced/terminal renal disease defined as serum creatinine clearance < 30 mL/min

• Active tuberculosis under treatment

• In case of HIV coinfection,

• Repeated ART failures and impossibility of prescription of an effective ART regimen

• Active opportunistic infection (OI)

• Current pregnancy or breast feeding

• Use of any drug known to interact with Sofosbuvir or Daclatasvir and for which temporary cessation or dose modification would be impossible

• Any concomitant medical condition that, according to the clinical site investigator, would contraindicate participation in the study

• Concurrent participation in any other clinical trial without written agreement of the two study investigators

Related Conditions & MeSH terms

• Communicable Diseases
• HCV Infection
• Hepatitis C
• Infections

Intervention

Drug:
• Sofosbuvir/Daclatasvir
Patients with a weight > 25 kg will be treated with a sofosbuvir/daclatasvir combination for 12 weeks with adult dose (400/60 mg), children with a weight between 14 and 25 kg will be treated with the same sofosbuvir/daclatasvir combination with the half adult dose (200/30 mg) for 12 weeks.

Locations

Country	Name	City	State
Cambodia	Battambang Provincial Hospital	Battambang
Cambodia	Kantha Bopha	Phnom Penh
Cambodia	National Pediatric Hospital	Phnom Penh
Cambodia	Jayavarman VII Hospital	Siem Reap

Sponsors (1)

Lead Sponsor	Collaborator
ANRS, Emerging Infectious Diseases

Country where clinical trial is conducted

Cambodia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Risk factors of HCV acquisition through questionnaire	Case-control study to evaluate the risk factors associated to HCV acquisition. The questionnaire include information on family disease history, medical care received (injections, blood transfusion, surgery), dental care, tatoos, injecting drug user, use of traditional medicine, and sharing of hygiene tools.	24 months
Primary	Evaluation of the effectiveness of sofosbuvir/daclatasvir combination for children aged = 6 years old and adolescents with active HCV infection in Cambodia	The proportion of patients with sustained virologic response defined by HCV RNA below the lower limit of quantification range of the viral load (undetectable viral load) 12 weeks after discontinuation of study drugs (SVR12). Detectable HCV RNA at the SVR12 study visit, permanent discontinuation of DAA, death, discontinuation of the study (loss to follow-up, transfer-out) will be considered as failures.	24 months
Secondary	Evaluation of the liver-related events	Proportion of patients with symptomatic cirrhosis and evaluation of Child-Pugh score; Proportion of patients with APRI (AST to Platelet Index Ratio) score > 2 and/or FIB-4 (Fibrosis-4) score > 3.25; Proportion of patients with liver elasticity > 9 kPa; Proportion of patients with hepato-cellular carcinoma	24 months
Secondary	Occurrence of grade 3-4 adverse events (ANRS grading table);	Frequency, type and time to grade 3 or 4 adverse clinical or biological events. All adverse events will be graded according to the Division of AIDS ( DAIDS) grading table; Frequency, type and time to drug-related clinical or biological adverse reactions of grade 3 or 4 or leading to treatment interruption	24 months
Secondary	Adherence	The adherence to DAA treatment will be assessed by accountability (drug pill count)	24 months
Secondary	Maximal Plasma Concentration (Cmax) of DAA	Cmax of Sofosbuvir, GS-331007 and Daclatasvir measured in plasma samples	24 months
Secondary	Area under the plasma concentration versus time curve over the dosing interval (AUCtau) of DAA	AUCtau of Sofosbuvir, GS-331007 and Daclatasvir will be estimated by the linear up log down trapezoidal method	24 months