Contact information
Type
Scientific
Primary contact
Dr Michael Ward
ORCID ID
Contact details
30 Bond Street
8th floor Queen wing
Toronto
M5B 1W8
Canada
+1 416 864 5733
wardm@smh.toronto.on.ca
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
CT-PAH 001
Study information
Scientific title
Acronym
The PHACeT trial
Study hypothesis
The primary objective of this phase I clinical trial is to establish the safety of autologous progenitor cell-based gene delivery of human nitric oxide synthase (heNOS) in patients with severe symptomatic pulmonary arterial hypertension (PAH) refractory to conventional treatment.
Please note that, as of 24/09/2008, the anticipated end date of this trial has been updated from 08/05/2008 to 31/10/2009.
Ethics approval
This study was approved by the Research Ethics Board (REB) of St. Michael's Hospital in May 2006 (ref: REB 04-253)
Study design
Phase I, open-label, non-randomised, dose-escalation trial. Doses are assigned sequentially.
Primary study design
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Idiopathic pulmonary arterial hypertension
Intervention
A total of 18 patients will be studied using an open-label, dose-escalating protocol; three patients will be entered into each of the five dosing panels. An additional three patients will be entered into the final dose panel to establish safety at the maximum tolerated dose.
Apheresis is performed to obtain mononuclear cells from the patientsÂ’ blood. These cells will then be engineered with human nitric oxide synthase (heNOS) and returned back to the patient (autologous) via the right ventricular port of a pulmonary arterial line in divided doses over a three-day elective hospitalisation. Follow-up hemodynamic measures are recorded at three months post-cell delivery.
Intervention type
Drug
Phase
Phase I
Drug names
Nitric oxide
Primary outcome measures
1. Tolerability and safety of the injection of genetically engineered progenitor cells in patients with severe PAH
2. Clinically significant changes in hemodynamic parameters
3. Time to clinical worsening
4. Contrast echo assessment of pulmonary arterial-venous shunting
5. Pulmonary function with diffusing capacity of the lung for carbon monoxide (DLCO)
6. Changes in ventilation perfusion scan
7. Dypnea by Borg index
8. Immune surveillance
9. Human nitric oxide synthase (heNOS) plasmid detection in systemic arterial blood pre- and post-cell delivery
Secondary outcome measures
Potential efficacy of this approach will be assessed by changes in hemodynamic pressures, patient perceived quality of life and exercise capacity.
Overall trial start date
08/05/2006
Overall trial end date
31/10/2009
Reason abandoned
Eligibility
Participant inclusion criteria
1. Age >=18 years and <=80 years
2. Clinical diagnosis of idiopathic PAH
3. Familial PAH or anorexigen-induced PAH
4. Specified 6-minute walk distance
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
18
Participant exclusion criteria
1. Intra or extra cardiac communication between the right- and left-sided circulations
2. Hemodynamic instability
3. Left ventricular ejection fraction <=40%
4. Thromboembolic event or recent hospitalisation for worsening right-sided heart failure in last three months
5. Central venous pressure (CVP) >20 mmHg at time of research heart catheterisation
6. Pregnancy
7. Concurrent hepatitis or HIV
Recruitment start date
08/05/2006
Recruitment end date
31/10/2009
Locations
Countries of recruitment
Canada
Trial participating centre
30 Bond Street
Toronto
M5B 1W8
Canada
Sponsor information
Organisation
Northern Therapeutics Inc (Canada)
Sponsor details
c/o Dr Duncan Stewart
725 Parkdale Avenue
Ottawa
Ontario
K1Y 4E9
Canada
+1 613 761 5341
djstewart@ohri.ca
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Northern Therapeutics Inc (Canada)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary