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Dendritic Cells Therapy Combined With Immunomodulatory Treatment in Multiple Sclerosis (TolDecCOMBINEM)

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ClinicalTrials.gov Identifier: NCT04530318
Recruitment Status : Recruiting
First Posted : August 28, 2020
Last Update Posted : December 21, 2022
Sponsor:
Information provided by (Responsible Party):
Judit Pich, Institut d'Investigacions Biomèdiques August Pi i Sunyer

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Relapsing-Remitting Multiple Sclerosis Other: Autologous peripheral blood differentiated adult tolerogenic dendritic cells expanded Other: Placebo Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Dendritic Cells Therapy Combined With Immunomodulatory Treatment in Multiple Sclerosis
Actual Study Start Date : January 27, 2020
Estimated Primary Completion Date : October 2024
Estimated Study Completion Date : October 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: TolDec
Autologous peripheral blood differentiated adult tolerogenic dendritic cells expanded
 Other: 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 Name: TolDec
Placebo Comparator: Placebo
Placebo of dendritic cells
 Other: Placebo
The infusion of the cells / placebo will take place at the Hospital Clínic de Barcelona (weeks 0, 2 and 4).


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]
  2. Proportion of patients with any Grade 3 -4 adverse events related to product administration during the study period. [ Time Frame: week 24 ]
  3. Proportion of patients with any Grade 3 -4 adverse events related to study product. [ Time Frame: week 24 ]

Secondary Outcome Measures :
  1. Proportion of patients with any Grade 3 -4 adverse events related to study product. [ Time Frame: week 24 ]
  2. Proportion of patients with any SAE events related to study product. [ Time Frame: week 24 ]
  3. Proportion of patients with at least one MS relapse during the study period. [ Time Frame: week 24 ]
  4. Total number of MS relapse at 24 weeks. [ Time Frame: week 24 ]
  5. Time to first MS relapse during the study period. [ Time Frame: week 24 ]
  6. Changes from baseline in the disability progression by Expanded Disability Status Scale (EDSS) at week 24. [ Time Frame: week 24 ]
  7. Changes from baseline in the disability progression by Multiple Sclerosis Functional Composite (MSFC) at week 24. [ Time Frame: week 24 ]
  8. Changes from baseline in the number of CUA lesion at week 24. [ Time Frame: week 24 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. Changes from baseline in brain global, white and gray matter volume and cervical cord volume on MRI at 24 weeks. [ Time Frame: week 24 ]
  13. Changes from baseline in the number of cortical lesions on MRI at 24 weeks. [ Time Frame: week 24 ]
  14. Changes from baseline in MR measurements of diffuse damage of brain tissue by MTR at 24 weeks [ Time Frame: week 24 ]
  15. Changes from baseline in MR measurements of relaxation times of T1 and T2 by MTR at 24 weeks. [ Time Frame: week 24 ]
  16. 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 ]
  17. 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 ]
  18. Changes from baseline in T cell proliferation to immunogenic peptides at 12 and 24 weeks. [ Time Frame: week 24 ]
  19. 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 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age between 18-65 years old.
  2. Patients diagnosed with RRMS according to 2017 McDonald criteria.
  3. MS disease duration < 10 years.
  4. Expanded disability status scale (EDSS) from 0 to < 5.5.
  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).
  6. Able to sign informed consent.
  7. 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:

  1. Presence of a relapse or use of steroids 30 days prior to screening visit.
  2. Concomitant use of any type of immunomodulatory / immunosuppressive therapy.
  3. 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.
  4. Patients unable or unwilling to undergo MRI scans.
  5. Severe systemic diseases or history of cancer or hereditary familiar cancer.
  6. Clinically relevant concomitant disease: cardiac, gastrointestinal, hepatic, pulmonary, neurological, renal or other major disease.
  7. Impossibility to proceed to the leukapheresis (e.g. absence of peripheral venous access).
  8. Pregnant or breastfeeding women.
  9. Drug or alcohol abuse.
  10. Patients with active systemic bacterial, viral or fungal infections, or known to have AIDS or to test positive for HIV antibody at screening.
  11. 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.
  12. 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).
  13. Dementia or severe psychiatric, cognitive or behavioral problems or other comorbidity that may interfere with the compliance to the protocol.
  14. 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.
  15. Participation in other experimental studies within the previous 90 days prior to screening visit.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04530318


Contacts
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Contact: Yolanda Blanco, MD +34932275414 yblanco@clinic.cat
Contact: Daniel Benitez dbenitezr@clinic.cat

Locations
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Spain
Hospital Moisés Broggi Recruiting
Hospitalet de Llobregat, Barcelona, Spain
Contact: Irati Zubizarreta, MD         
Hospital Universitari de Bellvitge Recruiting
Hospitalet de Llobregat, Barcelona, Spain
Contact: Lucía Romero, MD         
Hospital Clínic de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Yolanda Blanco, MD         
Hospital de Sant Pau Recruiting
Barcelona, Spain
Contact: Luis Querol, MD         
Hospital del Mar Recruiting
Barcelona, Spain
Contact: Elvira Munteis, MD         
Sponsors and Collaborators
Judit Pich
Investigators
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Study Chair: Yolanda Blanco, MD Hospital Clinic of Barcelona
More Information
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Responsible Party: Judit Pich, Clinical Research Manager. CTU Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer
ClinicalTrials.gov Identifier: NCT04530318    
Other Study ID Numbers: TolDec-COMBINEM
2020-000737-41 ( EudraCT Number )
First Posted: August 28, 2020    Key Record Dates
Last Update Posted: December 21, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
 Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases