Research Study on the Immunosuppressive Effects of a Cell Therapy Product on PBMC Isolated From Blood of Patients With Inflammatory Rheumatic Diseases

Laboratory Research Study of the Immunosuppressive Effect of a Cell Therapy Product on PBMC Isolated From Blood of Patients With Inflammatory Rheumatic Diseases

Rheumatic diseases regroup a variety of disorders affecting the locomotor system including joints, muscles, connective tissues and soft tissues around the joints and bones. Inflammation and/or autoimmune reactions contribute to the aetiology of many rheumatic diseases. Such autoimmune conditions, commonly referred to as inflammatory rheumatic diseases (IRD), include arthritis of various origins such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) or spondylarthritis (SpA). Patients with autoimmune diseases such as RA or SpA are in higher risk of fractures compared to the general population.

Initial pharmacotherapies for IRD remain NSAID treatment for pain relief, and anti-resorptive agents (e.g., TNF-alpha blockers) which aim at reducing bone loss and preventing occurrence of new bone erosions. Yet current treatments may have strong side effects and are not always effective (e.g., 35-40% of the patients treated with TNF-alpha inhibitors will initially or progressively loose response). Therefore there is a need for further treatment modalities in IRD, which would focus on both suppressing inflammation and treating bone disorders.

Current research studies indicate that Bone Therapeutics' allogeneic osteoblastic cells exhibit in vitro potent immunosuppressive and anti-inflammatory properties (in addition to osteo-regenerative and immune-privileged properties).

The present research study aims at investigating in vitro the properties of these osteoblastic cells in the context of inflammatory rheumatic diseases. In this purpose, in vitro assays will be used to test these immunosuppressive effects on peripheral blood mononuclear cells (PBMCs) of subjects diagnosed with RA, PsA and SpA.

Study Overview

• Status: Terminated
• Conditions: Rheumatoid Arthritis; Spondylarthritis; Psoriatic Arthritis
• Intervention / Treatment: Other: Blood sampling

• Study Type: Observational
• Enrollment (Actual): 30

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Rheumatoid Arthritis, Psoriatic Arthritis and Spondylarthritis Subjects

Description

Inclusion Criteria:

• Subjects of 18 years of age or older
• Subjects must belong to one of this group: Rheumatoid Arthritis (RA) Subjects OR Psoriatic Arthritis (PsA) Subjects OR Spondylarthritis (SpA) Subjects

Exclusion Criteria:

• Subjects diagnosed with other autoimmune/inflammatory diseases other than Crohn's disease, psoriasis, uveitis, Sjögren's syndrome and auto-immune thyroiditis
• Subjects with an active cancer and currently receiving a cancer treatment
• Women with known pregnancy
• Breastfeeding women
• Subjects with a known history of HIV and/or Hepatitis B and/or Hepatitis C infection and/or positive for HBs antigens

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Rheumatoid Arthritis; Patients with Rheumatoid Arthritis	Other: Blood sampling
Psoriatic Arthritis; Patients with Psoriatic Arthritis	Other: Blood sampling
Spondylarthritis; Patients with Spondylarthritis	Other: Blood sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PBMC proliferation, as assessed with PBMC assay	Freshly prepared cell therapy product and PBMC will be mixed together in wells. Mixes will be incubated for 7 days in a humidified atmosphere of 5% CO2 in air at 37°C. PBMC proliferation will be assessed using tritiated (³H)-thymidine uptake (β-counter).	7 days
Secretion of pro-inflammatory cytokines (e.g., IL-1β) and anti- inflammatory cytokines (e.g., IL-10), as assessed with PBMC assay	Freshly prepared cell therapy product and PBMC will be mixed together in wells. Mixes will be incubated for 7 days in a humidified atmosphere of 5% CO2 in air at 37°C. Pro-inflammatory cytokines (e.g., IL-1β) and anti- inflammatory cytokines (e.g., IL-10) will be measured in culture supernatant using Luminex method.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Record of past and current relevant medical history through questionnaire		time of first visit
Record of concomitant medications through questionnaire		time of first visit
Record of disease activity assessment (DAS28 and/or CASPAR and/or ASDAS and/or NY)		time of first visit
Record of any adverse events (if any)	occurring during and/or after the blood sample collection procedure	time of first visit
Results of the laboratory blood tests for CBC, RF, CRP, HLA-B27	Complete Blood Count (CBC), formula and electrolytes; Rheumatoid Factor (RF); C-Reactive Protein (CRP); HLA-B27	7 days

Collaborators and Investigators

• Sponsor: Bone Therapeutics S.A

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): June 4, 2017

Study Registration Dates

• First Submitted: June 3, 2015
• First Submitted That Met QC Criteria: February 27, 2018
• First Posted (Actual): March 6, 2018

Study Record Updates

• Last Update Posted (Actual): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 9, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Inflammation; Psoriatic Arthritis; Rheumatoid Arthritis; Rheumatic diseases; Autoimmune diseases; Spondylarthritis; Osteoimmunology
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Psoriasis; Bone Diseases, Infectious; Arthritis; Arthritis, Rheumatoid; Arthritis, Psoriatic; Rheumatic Diseases; Collagen Diseases; Spondylitis; Spondylarthritis
• Other Study ID Numbers: RAPSASPA-HBM