Dendritic Cells Therapy Combined With Immunomodulatory Treatment in Multiple Sclerosis

Relapsing-Remitting Multiple Sclerosis Clinical Trial

— TolDecCOMBINEM  

Official title:

Dendritic Cells Therapy Combined With Immunomodulatory Treatment in Multiple Sclerosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04530318
• Other study ID #: TolDec-COMBINEM
• Secondary ID: 2020-000737-41
• Status: Recruiting
• Phase: Phase 2
• Start date: January 27, 2020
• Est. completion date: June 2025

Study information

• Verified date: March 2024
• Source: Institut d'Investigacions Biomèdiques August Pi i Sunyer
• Contact: Yolanda Blanco, MD
• Phone: +34932275414
• Email: yblanco[@]clinic.cat
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing-Remitting Multiple Sclerosis
• Sclerosis

Intervention

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

Locations

Country	Name	City	State
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital de Sant Pau	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Moisés Broggi	Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitari de Bellvitge	Hospitalet de Llobregat	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Judit Pich

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes from baseline in the number of CUA lesion (mean number of the sum at week 12, 18 and 24).		week 12, 18 and 24
Primary	Proportion of patients with any Grade 3 -4 adverse events related to product administration during the study period.		week 24
Primary	Proportion of patients with any Grade 3 -4 adverse events related to study product.		week 24
Secondary	Proportion of patients with any Grade 3 -4 adverse events related to study product.		week 24
Secondary	Proportion of patients with any SAE events related to study product.		week 24
Secondary	Proportion of patients with at least one MS relapse during the study period.		week 24
Secondary	Total number of MS relapse at 24 weeks.		week 24
Secondary	Time to first MS relapse during the study period.		week 24
Secondary	Changes from baseline in the disability progression by Expanded Disability Status Scale (EDSS) at week 24.		week 24
Secondary	Changes from baseline in the disability progression by Multiple Sclerosis Functional Composite (MSFC) at week 24.		week 24
Secondary	Changes from baseline in the number of CUA lesion at week 24.		week 24
Secondary	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.		week 24
Secondary	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.		week 24
Secondary	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.		week 24
Secondary	Changes from baseline in brain global, white and gray matter volume and cervical cord volume on MRI at 24 weeks.		week 24
Secondary	Changes from baseline in the number of cortical lesions on MRI at 24 weeks.		week 24
Secondary	Changes from baseline in MR measurements of diffuse damage of brain tissue by MTR at 24 weeks		week 24
Secondary	Changes from baseline in MR measurements of relaxation times of T1 and T2 by MTR at 24 weeks.		week 24
Secondary	Changes in DTI measures as mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (Dr) and axial diffusivity (Da) at 24 weeks.		week 24
Secondary	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.		week 24
Secondary	Changes from baseline in T cell proliferation to immunogenic peptides at 12 and 24 weeks.		week 24
Secondary	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.		week 24