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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 3 August 2020
Main ID:  EUCTR2020-001157-48-GB
Date of registration: 09/07/2020
Prospective Registration: Yes
Primary sponsor: Imperial College London
Public title: PIPAH study: Using imatinib (drug) in Pulmonary Arterial Hypertension
Scientific title: Identifying a safe and tolerated dose of Imatinib for patients with Pulmonary Arterial Hypertension (PAH) - Positioning Imatinib for Pulmonary Arterial Hypertension (PIPAH)
Date of first enrolment: 28/07/2020
Target sample size: 43
Recruitment status: Authorised-recruitment may be ongoing or finished
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-001157-48
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: no
Randomised: no
Open: no
Single blind: no
Double blind: no
Parallel group: no
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: no
Placebo: no
Other: no
 
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no
Countries of recruitment
United Kingdom
Contacts
Name: Martin Wilkins   
Address:  Imperial College London W12 0HS NIHR Imperial CRF
Telephone: 02033136101
Email: m.wilkins@imperial.ac.uk
Affiliation:  Imperial College London
Name: Martin Wilkins   
Address:  Imperial College London W12 0HS NIHR Imperial CRF
Telephone: 02033136101
Email: m.wilkins@imperial.ac.uk
Affiliation:  Imperial College London
Key inclusion & exclusion criteria
Inclusion criteria:
1. Subjects aged between 18-75^ years old
2. PAH which is idiopathic, heritable or associated with anorexigens
3. Subjects homozygous at rs3816018 locus (PDGFRB genotype)*
*genotyped through the National Cohort Study
4. Resting mean pulmonary artery pressure >25 mmHg, Pulmonary
capillary wedge pressure =15 mmHg, PVR >5 wood units, and
normal or reduced cardiac output , as measured by right heart
catheterisation (RHC) at entry
5. Six-minute walking distance >50m at entry
6. Stable on an unchanged PAH therapeutic regime comprising at least
2 therapies licensed for PAH (any combination of endothelin receptor
antagonist, phosphodiesterase inhibitor or prostacyclin analogue) for
at least 1 month prior to screening
7. Able to provide written informed consent prior to any study
mandated procedures
8. Women of child-bearing potential are eligible to participate, if they agree to use one of the following contraception methods:
Abstinence OR
Highly effective contraceptive methods with typical-use failure rate
<1% i.e.
• Male or female sterilisation and long-acting reversible contraceptive methods (intrauterine devices and implants)prior to the female subject's entry into the study
• Progestogen-only injections if repeat rejections are documented as having been administered on schedule by a healthcare professional.

^The upper age limit stems from PAH Registries and previous clinical trials in the field.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

Exclusion criteria:
1. Unable to provide informed consent and/or non-fluent speaker of the English language
2. Hypersensitivity to Imatinib or to any of the excipients
3. Clinically-significant renal disease (confirmed by creatinine clearance <30 ml/min per 1.73m2)
4. Clinically-significant liver disease (confirmed by serum transaminases >3 times than upper normal limit)
5. Patients receiving oral and/or parenteral anticoagulants
6. Anaemia confirmed by haemoglobin concentration <10 g/dl
7. History of thrombocytopenia
8. Individuals known to have haemoglobinopathy sickle cell disease, thalassaemia
9. Hospital admission related to PAH or change in PAH therapy within 3 months prior to screening
10. History of left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following:
a. aortic or mitral valve disease (stenosis or regurgitation) defined as greater than mild aortic insufficiency, mild aortic stenosis, mild mitral stenosis, moderate mitral regurgitation
b. Mechanical or bioprosthetic cardiac valve
c. Pericardial constriction, effusion with tamponade physiology, or abnormal left atrial size.
d. Restrictive or congestive cardiomyopathy
e. Left ventricular ejection fraction =50% (measured in echocardiogram at screening)
f. Symptomatic coronary disease
g. Significant (2+ for regurgitation) valvular disease other than tricuspid or pulmonary regurgitation
h. Acutely decompensated left heart failure within 1 month of screening
i. History of untreated obstructive sleep apnoea
11. Evidence of significant lung disease on high-resolution CT (if available) or recent (performed within 12 months) lung function, where FEV1 < 50% predicted and FVC < 70% predicted, and DLCO (or TLCO) < 50% predicted if any CT abnormalities; judged by the Site Physician
12. Patients with a history of uncontrolled systemic hypertension
13. Acute infection (including eye, dental, and skin infections)
14. Chronic inflammatory disease including HIV, and Hepatitis B
15. Women of childbearing potential who are pregnant or breastfeeding
16. Previous intracerebral haemorrhage
17. Patients who have received an Investigational Medicinal Product (IMP) within 1 month before the baseline visit


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Pulmonary Arterial Hypertension (Idiopathic, heritable, or assosicated with anorexigens)
MedDRA version: 21.1 Level: LLT Classification code 10036727 Term: Primary pulmonary hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
MedDRA version: 21.1 Level: PT Classification code 10037400 Term: Pulmonary hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
MedDRA version: 21.1 Level: PT Classification code 10037400 Term: Pulmonary hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
MedDRA version: 21.1 Level: LLT Classification code 10068739 Term: Chronic thromboembolic pulmonary hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
MedDRA version: 20.0 Level: PT Classification code 10050701 Term: Congenital pulmonary hypertension System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 20.0 Level: PT Classification code 10050701 Term: Congenital pulmonary hypertension System Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
Intervention(s)

Trade Name: Imatinib mesilate
Product Name: Imatinib mesilate
Pharmaceutical Form: Tablet
INN or Proposed INN: Imatinib mesilate

Primary Outcome(s)
Main Objective: The over-aching hypothesis is that there is a subgroup of patients, identifiable by genotype, with pulmonary arterial hypertension that will benefit from a safe and tolerated dose of Imatinib.

Imatinib is thought to work by blocking a protein called platelet derived growth factor receptor B. There is a gene that regulates the blood levels of this protein, called the “PDGFRB”. Patients can be divided into 3 groups based on variants of this PDGFRB gene; the 3 groups are called CC, CT and TT. Patients with CC have higher levels of PDGFRB than patients with TT. It is possible that Imatinib works better in patients with CC than TT, and that patients who are in the CT group lie in between.

The study has two parts.

Part 1 will identify a maximum tolerated dose (MTD) of Imatinib in patients with pulmonary arterial hypertension. The MTD is defined by a dose with a 20% probability of leading to discontinuation of treatment for more than 5 consecutive days due to side effects.

Part 2 will ev
Primary end point(s): From a statistical point of view, the study has two parts.

Part 1: Discontinuation of the drug for more than 5 consecutive days due to Grade 2 or above Adverse Events defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (version .5.0, 2017), adapted for this study

Part 2: The primary efficacy endpoint is a binary variable. For patients with a baseline PVR >1000 dynes·s·cm-5, success is defined by an absolute reduction in PVR of =300 dynes·s·cm-5 at 24 weeks. For patients with a baseline PVR =1000 dynes·s·cm-5, success is a 30% reduction in PVR at 24 weeks.
Secondary Objective: -Change in the six-minute walk test, a measure of exercise capacity
-Change in echocardiogram (type of ultrasound heart test) values, a measure of how well the heart is working
-Change in "BNP" blood test values, another measure of heart function
-Change in Quality of Life scores

The above refer to change from baseline at 24 weeks.
Timepoint(s) of evaluation of this end point: After 24 weeks of treatment.
Secondary Outcome(s)
Secondary end point(s): -Change in 6MWD at 24 weeks.
-Change in right ventricular ejection fraction (RVEF) values, measured in echocardiogram (at screening visit and at 24 weeks).
-Change in plasma brain natriuretic peptide (proNT-BNP) levels from baseline at 24 weeks.
-Change in Quality of Life (QoL) scores from baseline at 24 weeks
Timepoint(s) of evaluation of this end point: After 24 weeks of treatment.
Secondary ID(s)
20HH5896
N/A
Source(s) of Monetary Support
Secondary Sponsor(s)
Ethics review
Status: Approved
Approval date: 28/07/2020
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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