Pulmonary arterial hypertension Respiratory
Conditions
Interventions
StratosPHere 2 is a double-blind, three-armed response-adaptive randomised controlled trial of two active arms (T1 = standard of care + hydroxychloroquine
T2 = standard of care + phenylbutyrate) and a control group (C = standard of care + placebo). The adaptation will be performed based on a Bayesian response-adaptive strategy, designed to dynamically a
Sponsors
Papworth Hospital NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Subjects eligible for enrolment in the study must meet all of the following criteria: 1. Aged between 18-75 years inclusive 2. Weight >40.0 kg at the Screening Visit 3. Having a diagnosis of group 1 PAH due to the following: Idiopathic or Heritable PAH with a known mutation in BMPR2 4. Being stable on an unchanged PAH therapeutic regime for at least 1 month prior to screening 5. Being competent to understand the information given in the approved Informed Consent Form and must sign the form prior to the initiation of any study procedures
Exclusion criteria
Exclusion criteria: PAH treatments: 1. Patients on TNF antagonists or other biological treatments 2. Subject has a known hypersensitivity to the Investigational Products, metabolites, or formulation excipients 3. Subject has a severe renal impairment (creatinine clearance 5 x upper limit of normal Haematology and bleeding disorders: 1. Subject has clinically significant anaemia in the opinion of the investigator, in particular from pyruvate kinase and G6PD deficiencies 2. Subjects with bleeding disorders or significant active peptic ulceration in the opinion of the investigator 3. Subject has peripheral blood platelets <100x109/L 4. Subject has a neutrophil count <2x109/L Cardiovascular: 1. Subject has had an acute myocardial infarction within the last 90 days prior to screening General medical conditions: 1. Subject with cardiovascular, liver, renal, haematologic, gastrointestinal, immunologic, endocrine, metabolic, or central nervous system disease that, in the opinion of the Investigator, may adversely affect the safety of the subject and/or efficacy of the investigational product or severely limit the lifespan of the subject other than the condition being studied 2. Subject has a history of malignancies within the past 5 years, except for a subject with localized, non-metastatic basal cell carcinoma of the skin, in situ carcinoma of the cervix, or prostate cancer who is not currently or expected, during the study, to undergo radiation therapy, chemotherapy, and/or surgical intervention, or to initiate hormonal treatment 3. History of known retinal disease 4. Currently taking any of the following contraindicated medications: 4.1. Chloroquine 4.2. Halofantrine 4.3. Amiodarone 4.4. Moxifloxacin 4.5. Cyclosporin 4.6. Mefloquine 4.7. Praziquantel 4.8. Prochlorperazine 4.9. Fluconazole 4.10. Penicillamine 4.11. Ivabridine General Criteria: 1. Female subject who is pregnant or breastfeeding 2. Subject has demonstrated noncompliance with previous medical regimens 3. Subject has a recent (within 1 year) history of abusing alcohol or illicit drugs 4. Subject has participated in a clinical study involving another investigational drug or device within 4 weeks before the Screening Visit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Target engagement of the BMPR2 pathway determined by change in peripheral blood-based BMPR2 function is measured by changes in the expression of a panel of eight BMPR2-modulated genes (i.e., ID3, SMAD1, SMAD5, NOTCH1, NOTCH2, ID2, ARL4C, PTGS2) using quantitative PCR from baseline (study entry/randomisation) to 8 weeks follow-up (8 weeks from treatment initiation) | — |
Secondary
| Measure | Time frame |
|---|---|
| BMPR2 cell surface protein expression on peripheral blood white cells, measured using flow cytometry at baseline and 8, 16 and 20 weeks | — |
Countries
England, Scotland, United Kingdom
Contacts
Public ContactEllen Temple-Jones
Outcome results
None listed