- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05767918
StratosPHere (Non-interventional Study)
StratosPHere: Optimal Biomarkers to Ascertain Target Engagement in Therapies Targeting the BMPR2 Pathway in Pulmonary Arterial Hypertension (PAH)
Study Overview
Status
Detailed Description
Pulmonary arterial hypertension (PAH) is a devastating and life-threatening disease that is associated with high morbidity and mortality. The disease is characterised by increased pulmonary arterial pressure; the blood pressure of the arteries found in the lungs. This increase in pressure is due to the progressive narrowing and obliteration of these blood vessels, often leading in failure of the right ventricle of the heart.
Current treatments for PAH utilise vasodilators to lessen the effects of the narrowing of the blood vessels and reduce blood pressure. However, a major breakthrough in our understanding of the molecular basis of PAH has been the identification of mutations, or changes, in important genes involved in the normal function of the lung vasculature. Mutations in the gene encoding bone morphogenetic protein type II receptor (BMPR2) have, to date been the most important genetic mutation identified, present in the majority (75%) of heritable PAH cases and approximately 11-44% of idiopathic cases (Dunmore et al). Such mutations result in a significantly reduced amount of this receptor on key cells in the pulmonary vasculature, the result of which is disruption of the normal cellular events and the subsequent development of vascular disease. Extensive research now exists on the role of BMPR2 in the development of PAH and pre-clinical findings support the targeting of BMPR2 as a potential treatment, however there are currently no therapeutics targeting the receptor in development.
To define the optimal biological biomarker end point of BMPR2 target engagement we will assess two study populations over a longitudinal time-course using peripheral blood samples.
Samples will be taken from a patient population with idiopathic or hereditary pulmonary arterial hypertension (n=17) and healthy volunteers (n=30) who will act as a control group.
Recruitment of healthy volunteers will be targeted at female aged 30-40 years as this is in line with the demographics of a typical PAH patient cohort. Blood samples will be collected from the control group across a total of 6 time points; the first 5 samples will be offered on a weekly basis with a final blood sample taken at 4 months. Sampling on weeks 2, 3, 4 and 16 will be optional. The expected duration for healthy volunteers is a total of 5 weeks with no follow up.
PAH participants will be sampled during routine clinic reviews over a four-month time period. Sampling will occur at separate two distinct time-points, three to six months apart. IPAH/HPAH participants will be recruited based upon their diagnosis and will be in WHO functional class I-IV and on stable medication or have unchanged PAH for at least one month prior to screening. The total duration for participants in this group will be approximately 3-6 months (typically 4 months), dependent on scheduling of clinical visits.
This will provide critical information for a future RCT testing two novel therapies with the potential to improve survival and quality of life for people diagnosed with PAH by providing a personalised approach to treatment.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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England
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Cambridge, England, United Kingdom, CB2 0QQ
- University of Cambridge Heart and Lung Research Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
Healthy volunteers
- Individual must be 18 years of age or over
- Weigh > 40kg at screening visit / BMI under 35
- Healthy and well at each visit
PAH participants
- Must have a diagnosis of IPAH or HPAH with a WHO functional class I-IV
- Must be on stable or unchanged PAH therapeutics for at least one month prior to screening visit
Exclusion Criteria:
Health volunteers
- Known hepatitis B, HIV or tuberculosis
- Clinically severe anaemia or bleeding disorders
PAH participants
- Other forms of PH besides IPAH or HPAH
- Patients on TNF antagonists of other biological treatments
- Known hepatitis B, HIV or tuberculosis
- Clinically severe anaemia or bleeding disorders
- Female participants who are pregnant or breast feeding
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Biomarker(s) identification
Time Frame: 2 years
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identify one or more biomarkers of increased BMPR2 expression or BMPR2 target engagement that fit a criterion of being reproducible and repeatable.
We will define the acceptable level of variability of these in order to be used in the subsequent phase 2a trial that will be powered to detect a 30% increase in BMPR2, and or BMPR2 target engagement with an 80% power in the known patient population.
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2 years
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Collaborators and Investigators
Investigators
- Principal Investigator: Mark Toshner Associate Professor MD FRCP, University of Cambridge
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- P02739
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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