- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04530318
Dendritic Cells Therapy Combined With Immunomodulatory Treatment in Multiple Sclerosis (TolDecCOMBINEM)
March 26, 2024 updated by: Judit Pich
The aim of this project is to assess properly the clinical efficacy of TolDec therapy by imaging, clinical and surrogate end-points related with the activity of the disease.
Study Overview
Status
Recruiting
Conditions
Detailed Description
Our working hypothesis is to make a combination therapy with low-moderate efficacy immunomodulatory drugs with the aim of increasing efficacy without causing serious adverse effects such as those associated with the available high-efficacy therapies.
Cellular therapies represent a highly specific treatment aimed to target selective "pathogenic" cells subsets.
Tol-Dec loaded with immunogenic peptides interacts with Ag-specific T lymphocytes inducing regulatory T cells without affecting other cell subsets leading to a antinflammatory shift of immunological responses.
Study Type
Interventional
Enrollment (Estimated)
45
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Yolanda Blanco, MD
- Phone Number: +34932275414
- Email: yblanco@clinic.cat
Study Contact Backup
- Name: Daniel Benitez
- Email: dbenitezr@clinic.cat
Study Locations
-
-
-
Barcelona, Spain
- Recruiting
- Hospital de Sant Pau
-
Contact:
- Luis Querol, MD
-
Barcelona, Spain
- Recruiting
- Hospital Del Mar
-
Contact:
- Elvira Munteis, MD
-
Barcelona, Spain, 08036
- Recruiting
- Hospital Clinic de Barcelona
-
Contact:
- Yolanda Blanco, MD
-
-
Barcelona
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Hospitalet de Llobregat, Barcelona, Spain
- Recruiting
- Hospital Moisés Broggi
-
Contact:
- Irati Zubizarreta, MD
-
Hospitalet de Llobregat, Barcelona, Spain
- Recruiting
- Hospital Universitari de Bellvitge
-
Contact:
- Lucía Romero, MD
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Age between 18-65 years old.
- Patients diagnosed with RRMS according to 2017 McDonald criteria.
- MS disease duration < 10 years.
- Expanded disability status scale (EDSS) from 0 to < 5.5.
- Patients eligible to start or already are in on treatment with first line immunomodulatory treatment (interferon beta 1a, interferon beta 1b, glatiramer acetate, teriflunomide or dymethyl-fumarate).
- Able to sign informed consent.
- Women of child-bearing potential must have a negative pregnancy test in serum before the inclusion in the study and agree to use highly effective contraceptive methods during the study. Highly effective contraceptive methods will include: intrauterine device, bilateral tubal occlusion, vasectomized partner and sexual abstinence.
Exclusion Criteria:
- Presence of a relapse or use of steroids 30 days prior to screening visit.
- Concomitant use of any type of immunomodulatory / immunosuppressive therapy.
- Use of previous immunosuppressive or cytotoxic therapy in the last 6 months. Use of previous alemtuzumab, cladribine or bone marrow or stem cell transplant at any time.
- Patients unable or unwilling to undergo MRI scans.
- Severe systemic diseases or history of cancer or hereditary familiar cancer.
- Clinically relevant concomitant disease: cardiac, gastrointestinal, hepatic, pulmonary, neurological, renal or other major disease.
- Impossibility to proceed to the leukapheresis (e.g. absence of peripheral venous access).
- Pregnant or breastfeeding women.
- Drug or alcohol abuse.
- Patients with active systemic bacterial, viral or fungal infections, or known to have AIDS or to test positive for HIV antibody at screening.
- Ongoing known bacterial, viral or fungal infection (with the exception of onychomycosis and dermatomycosis), positive hepatitis B surface antigen or hepatitis C antibody tests at screening.
- Patients with a known history of syphilis or tuberculosis or test positive for syphilis (positive rapid plasma reagin, RPR) or tuberculosis (positive skin test) at screening. Active or latent tuberculosis (TB).
- Dementia or severe psychiatric, cognitive or behavioral problems or other comorbidity that may interfere with the compliance to the protocol.
- Any other clinically relevant medical or surgical condition, which, in the opinion of the investigator, would put the subject at risk by participating in the study.
- Participation in other experimental studies within the previous 90 days prior to screening visit.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: TolDec
Autologous peripheral blood differentiated adult tolerogenic dendritic cells expanded
|
The infusion of the cells / placebo will take place at the Hospital Clínic de Barcelona (weeks 0, 2 and 4).
Other Names:
|
Placebo Comparator: Placebo
Placebo of dendritic cells
|
The infusion of the cells / placebo will take place at the Hospital Clínic de Barcelona (weeks 0, 2 and 4).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Changes from baseline in the number of CUA lesion (mean number of the sum at week 12, 18 and 24).
Time Frame: week 12, 18 and 24
|
week 12, 18 and 24
|
Proportion of patients with any Grade 3 -4 adverse events related to product administration during the study period.
Time Frame: week 24
|
week 24
|
Proportion of patients with any Grade 3 -4 adverse events related to study product.
Time Frame: week 24
|
week 24
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Proportion of patients with any Grade 3 -4 adverse events related to study product.
Time Frame: week 24
|
week 24
|
Proportion of patients with any SAE events related to study product.
Time Frame: week 24
|
week 24
|
Proportion of patients with at least one MS relapse during the study period.
Time Frame: week 24
|
week 24
|
Total number of MS relapse at 24 weeks.
Time Frame: week 24
|
week 24
|
Time to first MS relapse during the study period.
Time Frame: week 24
|
week 24
|
Changes from baseline in the disability progression by Expanded Disability Status Scale (EDSS) at week 24.
Time Frame: week 24
|
week 24
|
Changes from baseline in the disability progression by Multiple Sclerosis Functional Composite (MSFC) at week 24.
Time Frame: week 24
|
week 24
|
Changes from baseline in the number of CUA lesion at week 24.
Time Frame: week 24
|
week 24
|
Proportion of patients free from CUA lesion, gadolinium-enhancing lesions on T1 MRI and new or enlarged lesions on T2-MRI thought the 24 weeks of study.
Time Frame: week 24
|
week 24
|
Changes from baseline in the number of Gd-enhancing T1 lesions by scan (mean number of the sum at week 12, 18 and 24) and at week 24.
Time Frame: week 24
|
week 24
|
Changes from baseline in number of new or enlarging T2 lesions by scan (mean number of the sum at week 12, 18 and 24) and at week 24.
Time Frame: week 24
|
week 24
|
Changes from baseline in brain global, white and gray matter volume and cervical cord volume on MRI at 24 weeks.
Time Frame: week 24
|
week 24
|
Changes from baseline in the number of cortical lesions on MRI at 24 weeks.
Time Frame: week 24
|
week 24
|
Changes from baseline in MR measurements of diffuse damage of brain tissue by MTR at 24 weeks
Time Frame: week 24
|
week 24
|
Changes from baseline in MR measurements of relaxation times of T1 and T2 by MTR at 24 weeks.
Time Frame: week 24
|
week 24
|
Changes in DTI measures as mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (Dr) and axial diffusivity (Da) at 24 weeks.
Time Frame: week 24
|
week 24
|
Changes from baseline in cytokine production (including IFNgamma, IL-17, IL-4 and IL-10) in response to specific peptide stimulation in peripheral blood mononuclear cells (PBMCs) culture supernatants at 12 and 24 weeks.
Time Frame: week 24
|
week 24
|
Changes from baseline in T cell proliferation to immunogenic peptides at 12 and 24 weeks.
Time Frame: week 24
|
week 24
|
Changes from baseline in immune cell subsets in PBMCs including PBMC subtypes, T lymphocytes subpopulations and Treg subsets, CD4 and CD8 GM-CSF 'encephalitogenic' T cells and T cell subtypes by activation memory phenotype at 12 and 24 weeks.
Time Frame: week 24
|
week 24
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Chair: Yolanda Blanco, MD, Hospital Clinic of Barcelona
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 27, 2020
Primary Completion (Estimated)
June 1, 2025
Study Completion (Estimated)
June 1, 2025
Study Registration Dates
First Submitted
August 25, 2020
First Submitted That Met QC Criteria
August 25, 2020
First Posted (Actual)
August 28, 2020
Study Record Updates
Last Update Posted (Actual)
March 27, 2024
Last Update Submitted That Met QC Criteria
March 26, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- TolDec-COMBINEM
- 2020-000737-41 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
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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