E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with rare Immune mediated inflammatory diseases (IMIDs) involving the lungs causing interstitial pneumonitis (IP).
|
|
E.1.1.1 | Medical condition in easily understood language |
Patients with rare lung auto-immune disease |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This project will address rare Immune mediated inflammatory diseases (IMIDs) involving the lungs. When left untreated, interstitial pneumonitis (IP) can lead to poor quality of life and increased mortality. The main objective of this study is to assess the effects of rituximab (RTX) as a rescue therapy for therapy resistant progressive IMID- IP patients. Specifically there is an assessment of (1) pulmonary function tests (PFTs) and (2) Quality of Life measurement
|
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are to assess the value of (1) various prognostic markers biomarkers (2) an innovative rituximab scan to visualize RTX target sites (3) cost effectiveness of the RTX treatment |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age 18 - 70 years
• No previous therapy with rituximab
• Diagnosis of severe and / or progressive IMID-IP by one of the following
- Clinical symptoms consistent with interstitial lung disease between 3 months and 3 years prior to screening and co-existing IMID
- FVC <50% pred. and/or DLCO <40% pred.
- Diagnosis of usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), Organizing pneumonia (OP) or a mixed form of UIP / NSIP / OP by either of the following:
Open or video-assisted thoracic surgery (VATS) lung biopsy showing definite or probable UIP / NSIP / OP
- HRCT scan showing definite or probable UIP / NSIP / OP / mixed
- Worsening as demonstrated by any one of the following within the past year:
> 10% decrease in FVC
> 15% decrease in DLCO
• Therapy resistance to 1st (corticosteroids) and 2nd line therapy (cyclophosamide, AZT)
|
|
E.4 | Principal exclusion criteria |
• Residual volume >120% predicted at screening
• DLco <25% of predicted value at screening
• Evidence of active infection
• Pregnancy or lactation
• Hematology lower than specified limits
• Positive HIV, hepatitis B or C serology
• Fever (> 37,9 °C)
• Previous allergic reaction to monoclonal antibodies (e.g. infliximab)
• Receipt of any vaccine, particularly live viral vaccines, within 4 weeks before first rituximab dose.
• NYHA IV heart failure
• Renal failure requiring dialysis
• History of unstable or deteriorating neurological disease
• Any medical condition, which in the opinion of the principal investigator and/or clinician, may be adversely affected by the participation of the study
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Lung function test parameters
- Diffusion Capacity for Carbon Monoxide (DLco)
- Forced Vital Capacity (FVC)
• Quality of life assessment over time
- SF-36
- EQ-5D
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
follow up 3, 6, 9 and 12 months after first dose treatment with rituximab |
|
E.5.2 | Secondary end point(s) |
Secondary (prediction)
• Imaging parameters:
- Immuno PET/CT: by Zr-89-rituximab
- HRCT: changes
- FDG PET-CT: SUV mean
• Specific molecular markers:
(ACE, sIL2R, CA 15.3, LDH, CRP, TH17/IL-17, CD27, IgD, IgG, IgM, specific chemokines and cytokines after multiplex analyses)
• Cost assessment of rituximab vs prevention or delay of lung lungtransplants
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
after inclusion of patients, rituximab treatment patients will be monitored. If the first 10 immuno-PET scans are positive, then the other 10 scans will be continued. Analysis of first 10 scans will be within 6 months, the biomarkers results and cost assessments follow at the end of the study. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |