Clinical trial NCT03715023: Anti-viral Effect of PC786 on RSV Infection on HSCT Recipients
Official title: A Double Blind, Placebo-controlled Study to Assess the Anti-viral Effect, Safety and Tolerability of Inhaled PC786 for the Treatment of Acute Respiratory Syncytial Virus (RSV) Infection in Adult Hematopoietic Stem Cell Transplant Recipients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Respiratory Syncytial Virus Infections
Keywords: RSV infection
Hematopoeitic stem cell transplant
Lead sponsor: Pulmocide Ltd
Sponsor class: INDUSTRY
First posted: 2018-10-22
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study tests the effects of an experimental drug PC786 in people infected with Respiratory Syncytial Virus (RSV). PC786 may be useful in treating patients infected with RSV as it works by interfering with the way the virus multiplies. PC786 is an inhaled medicine. Participants will be treated with SoC treatment (e.g. oral ribavirin and/or IV immunoglobulin), half of the participants will receive PC786 in addition and half will receive a placebo treatment. The study will take place at multiple sites in UK and will include approximately 30 participants. The maximum study duration will be about 4 weeks.


Eligibility criteria: Inclusion Criteria:

* Received an allogeneic or autologous hematopoietic stem cell transplant (HSCT) using any conditioning regimen
* Experienced new onset of at least one of the following respiratory symptoms ≤5 days before study Day 1:

Nasal congestion or stuffiness, runny nose (rhinorrhoea), cough, or sore throat OR Worsening of at least one of those symptoms, if symptoms are chronic OR Wheezing, sputum production, pleuritic chest pain, increased respiratory rate, signs on chest auscultation, hypoxia, increased supplemental oxygen requirement or new infiltrates on chest X-ray/CT

* A positive RSV diagnostic test
* Provided written informed consent

Exclusion Criteria:

* Is intubated and requires invasive ventilation
* Has received any investigational RSV vaccine after HSCT, or has received any monoclonal anti-RSV antibodies within 4 months or 5 half-lives before participation
* Treatment with intravenous ribavirin
* Positive for test for influenza or parainfluenza
* Significant untreated bacteraemia or fungaemia
* Significant untreated bacterial, fungal, or viral pneumonia
* Precluded from participating as a result of treatment with another investigational drug or participation in another clinical trial
* Other disease or condition which would preclude the subject's participation in a clinical trial
* Is receiving an antiretroviral protease inhibitor
* Has chronic, active hepatitis infection
* Known alcohol or drug abuse

Primary outcomes:
measure: RSV viral load measured in nasal secretions by reverse transcription quantitative PCR (RT-qPCR)
timeFrame: Day 1 to Day 3
measure: Proportion of participants reporting one or more treatment-emergent adverse event (TEAE)
timeFrame: Baseline to Day 28
measure: Proportion of participants who discontinue due to an adverse event
timeFrame: Baseline to Day 28
measure: Proportion of participants who meet the markedly abnormal criteria for 12-lead ECG assessment at lease once post dose
timeFrame: Baseline to Day 28
measure: Proportion of participants who meet the markedly abnormal criteria for vital signs assessment at lease once post dose
timeFrame: Baseline to Day 28
measure: Proportion of participants who meet the markedly abnormal criteria for safety laboratory assessment at lease once post dose
timeFrame: Day 1 to Day 28
measure: Proportion of participants who meet the markedly abnormal criteria for peak expiratory flow assessment at lease once post dose
timeFrame: Day 1 to Day 28
Secondary outcomes:
measure: Average change in RSV load measured in nasal secretion
timeFrame: Day 1 to Day 7
measure: Change in RSV load in nasal secretion
timeFrame: Baseline to Day 3
measure: Change in RSV load in nasal secretion
timeFrame: Baseline to Day 7
measure: Duration in viral shedding measured in nasal secretion
timeFrame: Day 1 to Day 28
measure: Determination of nasal concentrations of PC786
timeFrame: Days 1, 2, 3, 7, 14 and 28
measure: Maximum observed concentration (Cmax) of PC786 measured in plasma
timeFrame: Day 1, Pre-dose to 4 hours
measure: Trough plasma concentration (Ctrough) of PC786
timeFrame: Days 2 and 3, Pre-dose
measure: Area under the concentration versus time curve from time zero to time at 4 hours (AUC0-4) of PC786 in plasma
timeFrame: Day 1, Pre-dose to 4 hours
measure: Last quantifiable concentration (Ct last) of PC786 measured in plasma
timeFrame: Day 1, and multiple timepoints to Day 28
measure: Changes in RSV symptoms measured using a symptom diary card
timeFrame: Days 1, 2, 3, 4, 5, 6, 7, 14 and 28
measure: Proportion of participants developing lower respiratory tract infection (LRTI) or pneumonia
timeFrame: Day 1 to 28
measure: Proportion of participants progressing to invasive ventilation
timeFrame: Day 1 to 28
measure: Trends in oxygen saturation index
timeFrame: Day 1 to Day 7
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: Liverpool
country: United Kingdom
facility: Clatterbridge Cancer Centre NHS Foundation Trust
city: London
country: United Kingdom
facility: St Georges University Hospital
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospital NHS Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
Study officials:
affiliation: Pulmocide Ltd
name: Alison Murray
role: STUDY_DIRECTOR
References: