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

Primary Purpose

Relapsing-Remitting Multiple Sclerosis

Status

Recruiting

Phase

Phase 2

Locations

Spain

Study Type

Interventional

Intervention

Autologous peripheral blood differentiated adult tolerogenic dendritic cells expanded

Placebo

About this trial

This is an interventional treatment trial for Relapsing-Remitting Multiple Sclerosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Hospital Moisés BroggiRecruiting
Hospital Universitari de BellvitgeRecruiting
Hospital Clínic de BarcelonaRecruiting
Hospital de Sant PauRecruiting
Hospital del MarRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

TolDec

Placebo

Arm Description

Autologous peripheral blood differentiated adult tolerogenic dendritic cells expanded

Placebo of dendritic cells

Outcomes

Primary Outcome Measures

Changes from baseline in the number of CUA lesion (mean number of the sum at week 12, 18 and 24).

Proportion of patients with any Grade 3 -4 adverse events related to product administration during the study period.

Proportion of patients with any Grade 3 -4 adverse events related to study product.

Secondary Outcome Measures

Proportion of patients with any Grade 3 -4 adverse events related to study product.

Proportion of patients with any SAE events related to study product.

Proportion of patients with at least one MS relapse during the study period.

Total number of MS relapse at 24 weeks.

Time to first MS relapse during the study period.

Changes from baseline in the disability progression by Expanded Disability Status Scale (EDSS) at week 24.

Changes from baseline in the disability progression by Multiple Sclerosis Functional Composite (MSFC) at week 24.

Changes from baseline in the number of CUA lesion at 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.

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.

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.

Changes from baseline in brain global, white and gray matter volume and cervical cord volume on MRI at 24 weeks.

Changes from baseline in the number of cortical lesions on MRI at 24 weeks.

Changes from baseline in MR measurements of diffuse damage of brain tissue by MTR at 24 weeks

Changes from baseline in MR measurements of relaxation times of T1 and T2 by MTR at 24 weeks.

Changes in DTI measures as mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (Dr) and axial diffusivity (Da) at 24 weeks.

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.

Changes from baseline in T cell proliferation to immunogenic peptides at 12 and 24 weeks.

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.

Full Information

NCT ID

NCT04530318

First Posted

August 25, 2020

Last Updated

December 20, 2022

Sponsor

Judit Pich

1. Study Identification

Unique Protocol Identification Number

NCT04530318

Brief Title

Dendritic Cells Therapy Combined With Immunomodulatory Treatment in Multiple Sclerosis

Acronym

TolDecCOMBINEM

Official Title

Dendritic Cells Therapy Combined With Immunomodulatory Treatment in Multiple Sclerosis

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Recruiting

Study Start Date

January 27, 2020 (Actual)

Primary Completion Date

October 2024 (Anticipated)

Study Completion Date

October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Judit Pich

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Relapsing-Remitting Multiple Sclerosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

TolDec

Arm Type

Experimental

Arm Description

Autologous peripheral blood differentiated adult tolerogenic dendritic cells expanded

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo of dendritic cells

Intervention Type

Other

Intervention Name(s)

Autologous peripheral blood differentiated adult tolerogenic dendritic cells expanded

Other Intervention Name(s)

TolDec

Intervention Description

The infusion of the cells / placebo will take place at the Hospital Clínic de Barcelona (weeks 0, 2 and 4).

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

The infusion of the cells / placebo will take place at the Hospital Clínic de Barcelona (weeks 0, 2 and 4).

Primary Outcome Measure Information:

Title

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

Title

Proportion of patients with any Grade 3 -4 adverse events related to product administration during the study period.

Time Frame

week 24

Title

Proportion of patients with any Grade 3 -4 adverse events related to study product.

Time Frame

week 24

Secondary Outcome Measure Information:

Title

Proportion of patients with any Grade 3 -4 adverse events related to study product.

Time Frame

week 24

Title

Proportion of patients with any SAE events related to study product.

Time Frame

week 24

Title

Proportion of patients with at least one MS relapse during the study period.

Time Frame

week 24

Title

Total number of MS relapse at 24 weeks.

Time Frame

week 24

Title

Time to first MS relapse during the study period.

Time Frame

week 24

Title

Changes from baseline in the disability progression by Expanded Disability Status Scale (EDSS) at week 24.

Time Frame

week 24

Title

Changes from baseline in the disability progression by Multiple Sclerosis Functional Composite (MSFC) at week 24.

Time Frame

week 24

Title

Changes from baseline in the number of CUA lesion at week 24.

Time Frame

week 24

Title

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

Title

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

Title

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

Title

Changes from baseline in brain global, white and gray matter volume and cervical cord volume on MRI at 24 weeks.

Time Frame

week 24

Title

Changes from baseline in the number of cortical lesions on MRI at 24 weeks.

Time Frame

week 24

Title

Changes from baseline in MR measurements of diffuse damage of brain tissue by MTR at 24 weeks

Time Frame

week 24

Title

Changes from baseline in MR measurements of relaxation times of T1 and T2 by MTR at 24 weeks.

Time Frame

week 24

Title

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

Title

Time Frame

week 24

Title

Changes from baseline in T cell proliferation to immunogenic peptides at 12 and 24 weeks.

Time Frame

week 24

Title

Time Frame

week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yolanda Blanco, MD

Phone

+34932275414

yblanco@clinic.cat

First Name & Middle Initial & Last Name or Official Title & Degree

Daniel Benitez

dbenitezr@clinic.cat

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yolanda Blanco, MD

Organizational Affiliation

Hospital Clinic of Barcelona

Official's Role

Study Chair

Facility Information:

Facility Name

Hospital Moisés Broggi

City

Hospitalet de Llobregat

State/Province

Barcelona

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Irati Zubizarreta, MD

Facility Name

Hospital Universitari de Bellvitge

City

Hospitalet de Llobregat

State/Province

Barcelona

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lucía Romero, MD

Facility Name

Hospital Clínic de Barcelona

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yolanda Blanco, MD

Facility Name

Hospital de Sant Pau

City

Barcelona

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Luis Querol, MD

Facility Name

Hospital del Mar

City

Barcelona

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Elvira Munteis, MD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Dendritic Cells Therapy Combined With Immunomodulatory Treatment in Multiple Sclerosis

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