Pulmonary arterial hypertension
Conditions
Interventions
Trade Name: RoActemra
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Tocilizumab
CAS Number: 375823-41-9
Current Sponsor code: n/a
Other descriptive name: n/a
Concentr
Sponsors
Papworth Hospital NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria Patients eligible for enrolment in the study must meet all of the following criteria: Demographics 1. Subject must be between 18 and 70 years of age, inclusive, at the Screening visit 2. Subject must weigh >40 kg at the Screening Visit. PAH Diagnosis and Classification 3. Subjects must have a diagnosis of group 1 PAH due to the following: a. idiopathic or heritable PAH b. PAH associated with: i. connective tissue disease excluding SLE, RA and MCTD (e.g., limited scleroderma, diffuse scleroderma, or overlap syndrome) ii. drugs or toxins 4. Subject must have a current diagnosis of being in WHO Functional Class II-IV. 5. Subject must meet all of the following haemodynamic criteria by means of a RHC prior to screening: i. mPAP of =/> 25 mmHg ii. PVR =/> 300 dynes/sec/cm5 iii. PCWP or LVEDP of 300 to 500 dynes/sec/cm5 Subject must meet all of the following pulmonary function tests completed no more than 24 weeks before the Screening visit: i. Total lung capacity (TLC) =/> 60% of predicted normal and ii. Forced expiratory volume in one second (FEV1) =/> 60% of predicted normal Subjects are required to have a documented negative V/Q scan or pulmonary arteriogram confirming the absence of CTEPH prior to screening. 7. Subject must walk a distance of =/>100m at the screening visit. 8. Subject, with or without supplemental oxygen, must have a resting arterial oxygen saturation (SaO2) 85% as measured by pulse oximetry at the Screening Visit. General 9. Female subject of childbearing potential, if sexually active, must agree to use 2 reliable methods of contraception from the Screening Visit until study completion and for at least 4 months following the last dose of Investigational Product. Subjects who have had a Copper T 380A IUD or LNg 20 IUD inserted are not required to use additional methods of contraception. 10. Subject must agree not to participate in a clinical study involving another investigational drug or device throughout this study. 11. Subject must be competent to understand the information given in the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved ICF and must sign the form prior to the initiation of any study procedures. Subject must be on stable on an unchanged PAH therapeutic regime for at least 1 month prior to screening. 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 22 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: PAH Treatments 1. Subject is on a continuous intravenous or subcutaneous infusion. 2. Patients on TNF antagonists or other biological treatments 3. Subject has a known hypersensitivity to the Investigational Products, the metabolites, or formulation excipients. 4. Subject has severe renal impairment (creatinine clearance 5 x upper limit 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 with peripheral blood Platelets 50% stenosis in at least one vessel), either by invasive angiography or by CT Angiography • positive stress test with imaging (either pharmacologic or with exercise) • previous coronary artery surgery • chronic stable angina 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 diverticulitis, diverticulitis requiring antibiotic treatment, or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis, or other symptomatic lower GI conditions that might predispose a patient to perforations 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 |
|---|---|
| Main Objective: Can blocking the effects of the protein interleukin-6 with the drug tocilizumab safely reduce blood pressure in the lungs of patients with pulmonary arterial hypertension.;Secondary Objective: What are the effects of the drug tocilizumab on measures of: 1) Quality of life. 2) Patients exercise capacity. 3) The immune systems response measured by blood sampling.;Primary end point(s): Co primary end-points of: 1) Safety as defined by the incidence and severity of adverse events. 2) Pulmonary vascular resistance as measured by right heart catheter in dynes/sec/cm5.;Timepoint(s) of evaluation of this end point: Safety will be assessed continuously throughout the study and specifically at each study visit. Study visits are monthly with an additional safety visit 30 days from trial completion at 6 months. Pulmonary vascular resistance will be assessed at baseline and at study end at 6 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) 6 minute walking distance. This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes (the 6MWD). It evaluates the global and integrated responses of all the systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood, neuromuscular units, and muscle metabolism. 2) BORG dyspnoea scoring index. This is a questionnaire which measures perceived exertion used in the assessment of breathlessness. 3) N-Terminal pro-B-type Natriuretic Peptide.This peptide is released by the heart and is a surrogate measure of heart function 4) WHO Functional Class assessment/disease specific QOL assessment tools. We will utilise the CAMPHOR questionnaire which is an internationally validated disease specific questionnaire which measures quality of life, activity and symptom domains. 5) Analysis of flow cytometric based peripheral blood leucocyte immunophenotyping. we will subtype leucocyte populations known to be responsive to IL6 to assess the immune system and it's response to therapy. 6) Serum and plasma measurements of circulating cytokines using multiplex cytokine arrays. This is also intended to assess the immune system and it's response to therapy. ;Timepoint(s) of evaluation of this end point: Secondary endpoints 1)-4) will be assessed monthly throughout the trial. End-points 5) and 6) will be assessed at baseline and study end at 6 months only. | — |
Countries
United Kingdom
Contacts
Public ContactLouise Harlow
Papworth Hospital NHS Trust
Outcome results
None listed