Clinical trial NCT05854511: Pharmacokinetics, Safety, Efficacy and Acceptability of Daclatasvir Plus Sofosbuvir in HCV-infected Children
Official title: Pharmacokinetics, Safety, Efficacy and Acceptability Study of Daclatasvir/Sofosbuvir in Children Weighing 14-35 Kilograms With Chronic Hepatitis C Virus Infection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: HCV
Keywords: Daclatasvir
Sofosbuvir
Children
HCV
Pharmacokinetics
Safety
Efficacy
Acceptability
Lead sponsor: Ain Shams University
Sponsor class: OTHER
Collaborators: name: Cairo University
First posted: 2023-05-11
Enrollment: 30
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an interventional, single center, single arm clinical trial to assess the pharmacokinetics, safety, efficacy, and acceptability of daclatasvir plus sofosbuvir in treatment-naïve children weighing between 14 and 35 kg with chronic HCV GT 1-6 infection.

Detailed description: This is an interventional, single center, single arm clinical trial to assess the pharmacokinetics, safety, efficacy, and acceptability of daclatasvir plus sofosbuvir in treatment-naïve, children weighing between 14 and 35 kg with chronic HCV GT 1-6 infection.

All enrolled patients will receive daclatasvir 30 mg orally once daily plus sofosbuvir at a dose of 200 mg (2x 100 mg tablets) orally once daily for 12 weeks.

Patients will be followed closely for disease progression and any hypersensitivity or adverse reactions due to therapy. Laboratory values to be monitored at baseline are serum creatinine, bilirubin, Aspartate transaminase (AST), Alanine transaminase (ALT), viral load (VL).

patients will be recruited in each of two weight bands (14 to \< 17 kg and 17 to 35 kg). The study is mainly powered for non-compartmental pharmacokinetics determination of DCV, SOF and GS-331007. Patient recruitment will be done at Ain Shams university hospitals, Egypt. The study be will conducted after approval by the corresponding research ethical committee and obtaining an informed consent from the parents or the legal guardians, and -whenever applicable- an assent from the patients.

Total number of visits is 7 for patients who will complete the study, a screening visits, at the first day of therapy, at weeks 1, 4, 8, 12 and 24 after starting daclatasvir plus sofosbuvir. Patients who will complete their treatment schedule will come after 12 weeks for assessment of SVR. Duration of follow up will be 6 months from treatment initiation in addition to screening period (2-4 weeks).

Eligibility criteria: Inclusion Criteria:

* Children more than 3 years of age and weighing 14-35kg
* Infected with HCV genotypes 1-6
* Treatment Naïve HCV-infected children
* Signing a written consent form by the parent or the legal guardian, and -whenever applicable- an assent by the patient
* Screening laboratory values within predefined thresholds:

  1. Absolute neutrophil count ≥ 1,500/mm3
  2. Platelets \> 50,000 cells/mm3
  3. Albumin \> 3.5 mg/dL
  4. Prothrombin Time PT \< 4 sec above control Or International Normalized Ratio INR \<1.7 3
  5. Random blood glucose level within normal range (\> 70 mg/dL and \< 200 mg/dL)
  6. Serum creatinine \< 1.5 mg/dL

Exclusion Criteria:

* Co-infection with HIV, acute hepatitis A virus, or hepatitis B virus
* Clinical hepatic decompensation, i.e., Child-Turcotte-Pugh CTP class B or C (i.e., jaundice, ascites, encephalopathy, or variceal hemorrhage)
* Renal dysfunction, i.e., eGFR \< 60 mL/min/1.73 m2 or on regular dialysis as calculated by Schwartz Formula
* Alfa-fetoprotein level \> 50 ng/mL
* Chronic liver disease due to a cause other than HCV or Known hypersensitivity to daclatasvir or sofosbuvir.
* History of gastrointestinal disease or gastrointestinal surgical procedure that would impair the absorption of the study drug
* Blood/blood product transfusion within 4 weeks prior to study.
* Systemic corticosteroid administration for more than 2 weeks starting from two weeks before study inclusion and till the end of treatment period (pulmonary/nasal administration is permitted).
* Psychiatric hospitalization, suicide attempt or disability resulting from psychiatric illness within the prior 5 years.
* Ongoing treatment with any medications interacting with daclatasvir/sofosbuvir.

Primary outcomes:
measure: Plasma concentration of Daclatasvir
timeFrame: one week
measure: Plasma concentration of Sofosbuvir
timeFrame: one week
Secondary outcomes:
measure: Efficacy of Daclatasvir 30 MG oral tablets and Sofosbuvir 200 MG oral tablets once daily for 12 weeks
timeFrame: 24 weeks
measure: Safety of Daclatasvir 30 MG oral tablets and Sofosbuvir 200 MG oral tablets once daily for 12 weeks
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Faculty of Medicine, Ain-Shams University Research Institute-Clinical Research Centre (MASRI-CRC)
Study officials:
affiliation: Department of Paediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
name: Manal H. El-Sayed, MD
role: PRINCIPAL_INVESTIGATOR
References: