Secondary data use of tocilizumab clinical studies to address regulatory needs for rare and pediatric trials
| ISRCTN | ISRCTN13592648 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13592648 |
| European Commission funding Grant call | HORIZON-HLTH-2023-IND-06 |
| Sponsor | F. Hoffmann-La Roche |
| Funders | HORIZON EUROPE Health, Swiss State Secretariat for Education, Research and Innovation (SERI), UK Research and Innovation |
- Submission date
- 12/01/2026
- Registration date
- 16/01/2026
- Last edited
- 16/01/2026
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Musculoskeletal Diseases
Plain English summary of protocol
Background and study aims
Rare diseases (RD) affect up to 36 million people across the EU. Although many medicines have been authorized, 95% of these diseases still have no treatment options. It is difficult to test new drugs for rare diseases because there are very few patients, and their symptoms can vary widely. This makes it hard for regulators to decide if a new treatment is safe and effective.
The INVENTS project aims to solve these problems by using advanced computer modeling and simulation methods. By using existing data from previous clinical trials, researchers will develop new evidence tools and in silico trials (computer-simulated trials). These tools will help predict how well a treatment works, even when only a small amount of patient data is available. The goal is to make the drug approval process faster and more reliable so that patients with rare diseases can access life-saving treatments sooner.
Who can participate?
This specific study is a retrospective study, meaning it uses data that have already been collected from past clinical trials. No new patients are being recruited to join this study. The data used in this research comes from around 10,000 participants who took part in 20 previous studies of the drug tocilizumab. These participants included:
1. Adult patients with rheumatoid arthritis (a common inflammatory disease).
2. Adults and children with rare inflammatory diseases, including:
2.1. Polyarticular juvenile idiopathic arthritis
2.2. Systemic juvenile idiopathic arthritis
2.3. Giant cell arteritis
2.4 Systemic sclerosis
What does the study involve?
Researchers will analyze existing data from the 20 tocilizumab trials to build and test mathematical models. The study involves:
1. Data analysis: using computer software to look at how the drug moves through the body (pharmacokinetics) and how it affects the disease (pharmacodynamics).
2. Comparison: comparing traditional trial results with results generated by new modelling methods to see if the models are accurate.
3. Virtual patients: creating virtual patient cohorts to simulate how different groups of people might respond to a treatment.
The team will look at patient characteristics (like age and weight), drug doses, blood test results (like C-reactive protein), and physical symptoms (like joint swelling or skin thickness) and disease scores that were recorded in the original trials.
What are the possible benefits and risks of participating?
Because this study uses secondary data (information already collected years ago), there are no direct physical risks to the participants, and they do not need to take any new medications or attend extra appointments.
While individual participants do not benefit directly, the project will help future patients with rare diseases by making it easier and faster to develop and approve new treatments.
The main risk in this type of research is data privacy. To minimize this, all data is pseudonymized, meaning names, initials, and specific dates are removed or changed so that individuals cannot be easily identified. The data is kept in a highly secure environment managed by the Health Data Hub (HDH).
Where is the study run from?
The study is led by INSERM (the French National Institute of Health and Medical Research) in France. The data controller responsible for the project is F. Hoffmann-La Roche Ltd based in Basel, Switzerland. Research is carried out by a group (consortium) of experts from universities and institutions across Europe, including the UK, Netherlands, Austria, Sweden, the Netherlands and Germany.
When is the study starting and how long is it expected to run for?
The original clinical trials provided data from patients who were enrolled between 2005 and 2016. For this new research project, data analysis is scheduled to take place from November 2024 to October 2029. The results and the computer code used are expected to be published between 2027 and 2031.
Who is funding the study?
INVENTS has received funding from the European Union’s Horizon Europe Research and Innovation program under grant agreement 101136365, the Swiss State Secretariat for Education, Research and Innovation (SERI) and the UKRI Innovative UK under their Horizon Europe Guarantee scheme. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Health and Digital Executive Agency. Neither the European Union nor the granting authority can be held responsible for them.
Who is the main contact?
David Pau, david.pau@roche.com
Contact information
Public, Principal investigator, Scientific
Inserm, Inserm U1346 - Centre Inria Paris - Université Paris Cité
PariSanté Campus - 10 rue d'Oradour-sur-Glane
Paris
75015
France
 ORCID ID |
0000-0002-8429-2340 |
|---|---|
| Phone | +33 01 44 27 92 03 |
| sarah.zohar@inserm.fr |
Scientific, Public
4 cours de l'ile Seguin
Boulogne-Billancourt
92100
France
| ORCID ID |
0000-0001-7664-4521 |
|---|---|
| Phone | +33 0673995067 |
| david.pau@roche.com |
Study information
| Primary study design | Observational |
|---|---|
| Observational study design | Secondary data use of 20 studies (interventional and non-interventional) evaluating tocilizumab. |
| Scientific title | Innovative designs, extrapolation, simulation methods and evidence - tools for rare diseases addressing regulatory needs (INVENTS project) - secondary data use of tocilizumab clinical studies |
| Study acronym | INVENTs - tocilizumab |
| Study objectives | The Primary Objective of this study will be to describe per population of interest, the characteristics of patients exposed to tocilizumab from early-stage clinical trials to real-world studies. Exploratory objectives of this protocol are the objectives defined in the INVENTS project, submitted and accepted by the EU. The INVENTS project is based on 7 objectives: 5 major methodological objectives, 1 objective focused on regulatory perspectives and 1 objective dedicated to use cases useful for the research. All objectives are complementary and interconnected: Objective #1 (INVENTS Work package 1): Improving robustness of model-based treatment effect estimation and extrapolation methods Objective #2 (INVENTS Work package 2): Developing an in silico trials workflow using modelling and simulation, clinical trial and RWD to cope with missing knowledge Objective #3 (INVENTS Work package 3): Increasing robustness of small population confirmatory trials using validated and credible models Objective #4 (INVENTS Work package 4): Proposing evidence synthesis approaches using computational models, clinical studies, RWD and virtual cohorts Objective #5 (INVENTS Work package 5): Developing evidence-based tools for regulatory decision making in RD Objective #6 (INVENTS Work package 6): Integrating patient engagement and regulatory perspectives Objective #7(INVENTS Work package 7): provide use cases for the methods developed in work packages 1-5 and provide relevant data and disease area expertise. |
| Ethics approval(s) |
Approved 25/04/2024, CESRESS- Comité Éthique et Scientifique pour les Recherches, les Études et les Évaluations dans le domaine de la Santé (HDH, 9 rue Georges Pitard, Paris, 75015, France; -; hdh@health-data-hub.fr), ref: 17337354 |
| Health condition(s) or problem(s) studied | Systemic/polyarticular juvenile idiopathic arthritis, giant cell arteritis and rheumatoid arthritis |
| Intervention | The methods that will be developed during this study will enable the exploitation of novel and improved clinical trial designs, in silico trials and real-world data (including real-world data from patients’ care) analysis approaches supporting drug development in rare diseases. The European Medicine Agency and European national regulators (including Health Technology Assessment bodies) will be supplied with a general framework and evidence-tools allowing better informed decision-making thanks to reliable data augmentation techniques and tools allowing studies with small sample sizes to reach high level evidence, ideally matching the level obtained through large, randomized studies. Most importantly, small populations, including patients suffering from rare diseases, will benefit from an increased and faster access to efficacious and safe treatments. Beyond this project, this workflow could be used in other disease settings when evaluating small sample evidence which is the goal of precision medicine The mobilization of the clinical data from Roche clinical studies will allow the acquisition of a lot of additional knowledge to help improve consistency and efficiency of the drug evaluation process for rare disease by augmenting clinical evidence without compromising its scientific integrity and providing regulators assessment credibility criteria. |
| Intervention type | Drug |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | tocilizumab |
| Primary outcome measure(s) |
|
| Key secondary outcome measure(s) | |
| Completion date | 31/12/2029 |
Eligibility
| Participant type(s) | |
|---|---|
| Age group | All |
| Lower age limit | 1 Day |
| Upper age limit | 100 Years |
| Sex | All |
| Target sample size at registration | 111530 |
| Total final enrolment | 10096 |
| Key inclusion criteria | All patients included in the 20 clinical studies. |
| Key exclusion criteria | GDPR non compliant countries |
| Date of first enrolment | 01/01/2005 |
| Date of final enrolment | 01/01/2017 |
Locations
Countries of recruitment
- Scotland
- Argentina
- Australia
- Austria
- Belgium
- Brazil
- Bulgaria
- Canada
- Czech Republic
- Denmark
- France
- Germany
- Greece
- Hungary
- Israel
- Italy
- Mexico
- Netherlands
- Norway
- Poland
- Portugal
- Singapore
- Slovakia
- Spain
- Sweden
- Switzerland
- Thailand
- United States of America
Study participating centres
Eaton Road
West Derby
Liverpool
L12 2AP
England
London
WC1N 1EH
England
Aberdeen
AB25 2ZN
Scotland
Barnsley
S75 2EP
England
Welcome Building, Blue Zone
Edgbaston
Birmingham
B15 2TH
England
Turner Road
Colchester
CO4 5JL
England
Leeds
LS7 4SA
England
162 City Road
London
EC1V 2PD
England
High Heaton
Newcastle upon Tyne
NE7 7DN
England
Rom Valley Way
Romford
RM7 0AG
England
Stoke-on-trent
ST6 7AG
England
Treliske
Truro
TR1 3LJ
England
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Stored in non-publicly available repository |
| IPD sharing plan | The datasets to be used in INVENTS were collected during clinical trials. The participants received an information related to the processing of their data for the purpose of the trial. All but two of these clinical trials were conducted prior to the entry into force of GDPR and thus could not have satisfied the requirements introduced by this regulation. In addition, the INVENTS project was not foreseen at the time, and without GDPR, no re-information mechanism was planned. For concerned persons based in France, Roche will provide a collective information notice on its website (https://www.roche.fr/fr/patients/patient-information-portal.html), with the information content defined by GDPR article 14 in French and in English. |
Editorial Notes
16/01/2026: Study's existence confirmed by CESRESS - Comité Éthique et Scientifique pour les Recherches, les Études et les Évaluations dans le domaine de la Santé.
