Clinical trial NCT02654171: Viral Inhibition in Children for Treatment of RSV
Official title: A Randomized, Double-blind, Placebo-controlled, 2-Part Study of Orally Administered AK0529 to Evaluate the Safety, Tolerability, Pharmacokinetics and Antiviral Effect of Single and Multiple Dosing in Hospitalized Infants With Respiratory Syncytial Virus Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: RESPIRATORY SYNCYTIAL VIRUS INFECTIONS
Keywords: RSV
AK0529
Lead sponsor: Shanghai Ark Biopharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Ark Biosciences Pty Ltd.
First posted: 2016-01-13
Enrollment: 72
Sex: ALL
Minimum age (years): 1
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: VICTOR is a randomized, double-blind, placebo-controlled, multicenter, 2-part study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antiviral effect of single and multiple dosing of AK0529 in infants hospitalized with RSV infection.

Detailed description: Globally, Respiratory Syncytial Virus (RSV) is recognized as the leading cause of respiratory tract infections in infants and young children and a major cause of hospitalization due to severe respiratory infection. Despite four decades of effort, there are still no effective methods to control RSV infection. Treatment of RSV has been limited to supportive measures. There is an urgent need for safe and effective drugs to treat and prevent RSV disease.

AK0529 is an investigational antiviral agent that targets the RSV fusion protein on the surface of the viral envelope and exerts antiviral activity against RSV by inhibiting viral entry into host cells and preventing fusion protein induced cell-cell fusion. AK0529 was generally well tolerated in healthy volunteers.

This study is designed as a randomized, double-blind, placebo-controlled, multicenter, phase 2 study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antiviral effect of single and multiple dosing of AK0529 in infants hospitalized with RSV infection. It will consist of two parts, Part 1 and Part 2. Each part will consist of three phases, a pre-treatment phase, a treatment phase and post-treatment follow-up phase.

Eligibility criteria: Inclusion Criteria:

* Male or female patients of any race or ethnicity with an age adjusted for any prematurity of ≥1 month and ≤24 months.
* Diagnosis of RSV infection by virological means, which may include rapid diagnostic point-of-care testing, within 96 hours preceding screening for Part 1 and 72 hours for Part 2.
* Patient must weigh \>3 kg at screening and be within the 10th and 90th percentiles (inclusive) for the patient's age, based on the local child growth standards, i.e. the Australian Paediatric Endocrine Group Growth Charts.
* The parent / legal guardian of the patient must have provided written informed consent for the patient to participate.
* For patients aged \<12 months, an occipito-frontal head circumference within the normal range for age and gender.

Exclusion Criteria:

* The patient has taken, is currently taking or requires any restricted medications.
* Patient is known to be HIV-positive (or the mother, if the potential patient is a child aged \<6 months).
* Participation in an investigational drug or device study within 30 days prior to the date of screening.
* Requires vasopressors or inotropic support at the time of enrolment.
* Concurrent gastrointestinal conditions that could, in the opinion of the investigator, prejudice absorption of the Investigational Medicinal Product (e.g. protracted vomiting, malabsorption syndrome, a history of necrotising enterocolitis with consequent short gut syndrome).
* Bronchopulmonary dysplasia or chronic lung disease requiring assisted ventilation at the time of enrolment.
* Diminished ventilatory reserve at risk for hypercapnia (e.g. pulmonary hypoplasia, sequestration syndromes, cystadenomatoid malformation, a history of surgery for diaphragmatic hernia).
* Left to right shunt meriting corrective therapy.
* Renal failure including renal anomalies likely to be associated with renal insufficiency (e.g. clinical conditions of renal dysplasia, polycystic renal disease, renal agenesis).
* Clinical evidence of hepatic decompensation (e.g. hepatic disorder with associated coagulopathy or associated encephalopathy).
* Cerebral palsy with microcephaly, chronic or persistent feeding difficulties or seizures.
* Symptomatic because of inborn errors of metabolism (e.g. mitochondrial disorders, disorders of carbohydrate metabolism, glycogen storage disorders).
* Congenital or acquired immunodeficiency (e.g. congenital agammaglobulinaemia, common variable immunodeficiency, immunosuppressive therapy other than glucocorticoid or montelukast therapy forming part of care directed by the treating physician).
* For Part 2 of this study, children with a history of having received palivizumab or any other monoclonal agent directed against RSV in the preceding 120 days. This exclusion criterion does not apply to Part 1.
* Evidence of active or uncontrolled respiratory, cardiac, hepatic, central nervous system or renal disease unrelated to RSV infection at baseline or any other medical condition that in the opinion of the investigator renders the patient unsuitable for enrolment.
* A history of epilepsy or seizures including febrile seizures.
* Allergy to test medication or constituents.
* Weight less than 10th percentile or greater than 90th percentile for age and gender adjusted for any prematurity.
* The patient's parent or legally acceptable representative is an employee of the investigator or the study center, with direct involvement in the proposed study or other studies under the direction of that investigator of the study center, or any family members of the employees or the investigator.
* Failure to satisfy the investigator of fitness to participate for any other reason.

Primary outcomes:
measure: Incidence of Adverse Events during the study
timeFrame: Day -4 to single dose Day 7 (Part 1) and Day -3 to multiple dose Day 14 (Part 2)
measure: Subject withdrawals due to Adverse Events
timeFrame: Day -4 to single dose Day 7 (Part 1) and Day -3 to multiple dose Day 14 (Part 2)
Secondary outcomes:
measure: Area under the plasma concentration-time curve from time 0 to infinity (AUC)
timeFrame: Pharmacokinetic samples will be taken predose, 2, 4, 6, 12, 18, 24 hours postdose on Day 1, 48 hours postdose (Part 1 and Part 2) and Day 5 (Part 2 )
measure: Maximum plasma concentration of AK0529 (Cmax)
timeFrame: Pharmacokinetic samples will be taken predose, 2, 4, 6, 12, 18, 24 hours postdose on Day 1, 48 hours postdose (Part 1 and Part 2) and Day 5 (Part 2 )
measure: Plasma concentration of AK0529 at 12 hours postdose (C12)
timeFrame: Pharmacokinetic samples will be taken predose, 2, 4, 6, 12, 18, 24 hours postdose on Day 1, 48 hours postdose (Part 1 and Part 2) and Day 5 (Part 2 )
measure: Apparent total body clearance (CL/F)
timeFrame: Pharmacokinetic samples will be taken predose, 2, 4, 6, 12, 18, 24 hours postdose on Day 1, 48 hours postdose (Part 1 and Part 2) and Day 5 (Part 2 )
measure: Apparent central compartment volume of distribution (Vc/F)
timeFrame: Pharmacokinetic samples will be taken predose, 2, 4, 6, 12, 18, 24 hours postdose on Day 1, 48 hours postdose (Part 1 and Part 2) and Day 5 (Part 2 )
measure: Area under curve change of viral load
timeFrame: From baseline to Day 5
measure: Incidence of F-protein genotypes
timeFrame: Specimen will be collected predose and 24 hours postdose on Day 1 (Part 1) and on Day 1-5 (Part 2).
measure: Change of symptom score
timeFrame: From baseline to Day 1 (Part 1) and up to Day 5 after multiple drug administration (Part 2).
Other outcomes:
Locations:
city: Gold Coast
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Lady Cilento Children's Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Women's and Children's Hospital
state: South Australia
city: Sha Tin
country: Hong Kong
facility: Prince of Wales Hospital
city: Beer-Sheva
country: Israel
facility: Soroka University Medical Center
city: Haifa
country: Israel
facility: Ruth Rappaport Children's Hospital
city: Petach Tikvah
country: Israel
facility: Schneider Children's Medical Center
city: Beirut
country: Lebanon
facility: American University of Beirut Medical Center
city: Beirut
country: Lebanon
facility: Makassed General Hospital
city: Beirut
country: Lebanon
facility: Rafik Hariri University Hospital
city: Beirut
country: Lebanon
facility: Saint George Hospital University Medical Center
city: Seremban
country: Malaysia
facility: Hospital Tuanku Jaafar
state: Negeri Sembilan
city: Sibu
country: Malaysia
facility: Hospital Sibu
state: Sarawak
city: Batu Caves
country: Malaysia
facility: Hospital Selayang
state: Selangor
city: Klang
country: Malaysia
facility: Hospital Tengku Ampuan Rahimah
state: Selangor
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Center
city: Poznań
country: Poland
facility: Specjalistyczny Zespół Opieki Zdrowotnej nad Matką i Dzieckiem w Poznaniu
state: Greater Poland
city: Świecie
country: Poland
facility: Nowy Szpital w Świeciu
state: Kujawy-Pomerania
city: Trzebnica
country: Poland
facility: Szpital im. Świętej Jadwigi Śląskiej w Trzebnicy
state: Trzebnica County
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Municipal Wanfang Hospital
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
city: Adana
country: Turkey
facility: Cukurova University Balcali Hospital
state: Adana Province
city: Eskişehir
country: Turkey
facility: Eskisehir Osmangazi University Faculty of Medicine
state: Eskişehir Province
city: İzmir
country: Turkey
facility: Ege University Medical Faculty
state: İzmir Province
city: İstanbul
country: Turkey
facility: Marmara University Faculty of Medicine
Study officials:
affiliation: info@arkbiosciences.com
name: Ark Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ, O'Brien KL, Roca A, Wright PF, Bruce N, Chandran A, Theodoratou E, Sutanto A, Sedyaningsih ER, Ngama M, Munywoki PK, Kartasasmita C, Simoes EA, Rudan I, Weber MW, Campbell H. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010 May 1;375(9725):1545-55. doi: 10.1016/S0140-6736(10)60206-1.
citation: Huang LM, Schibler A, Huang YC, Tai A, Chi H, Chieng CH, Wang JL, Goldbart A, Tang SP, Huang YC, George S, Alabaz D, Bentur L, Su SC, de Bruyne J, Karadag B, Gu F, Zou G, Toovey S, DeVincenzo JP, Wu JZ. Safety and efficacy of AK0529 in respiratory syncytial virus-infected infant patients: A phase 2 proof-of-concept trial. Influenza Other Respir Viruses. 2023 Jul 25;17(7):e13176. doi: 10.1111/irv.13176. eCollection 2023 Jul.