Mesenchymal Precursor Cells (MPCs) for treatment of rheumatoid arthritis

• Register: EUCTR
• Last refreshed on: 17 February 2014
• Main ID: EUCTR2012-005674-61-LV
• Date of registration: 13/09/2013
• Prospective Registration: Yes
• Primary sponsor: Mesoblast, Inc
• Public title: Mesenchymal Precursor Cells (MPCs) for treatment of rheumatoid arthritis
• Scientific title: A double-blind, randomized, placebo-controlled, multi-center, dose escalation study of a single intravenous infusion of Allogeneic Mesenchymal Precursor Cells (MPCs) in the treatment of biologic-naïve patients with rheumatoid arthritis
• Date of first enrolment: 13/09/2013
• Target sample size: 90
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-005674-61
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: yes Other trial design description: Dose escalation If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Belgium, Croatia, Czech Republic, Estonia, Hungary, Latvia, Poland, Serbia

Contacts

• Name: Clinical Trials Information
• Affiliation: Mesoblast UK Limited

• Name: Clinical Trials Information
• Affiliation: Mesoblast UK Limited

Key inclusion & exclusion criteria

Inclusion criteria:
- Provision of informed consent
- Males and females 18 - 80 years of age.
- Active rheumatoid arthritis (RA) diagnosed according to the 2010 ACR/EULAR classification criteria. Patients must be positive for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP3) antibodies and must have early (6 months – 2 years disease duration) RA but without the poor prognostic features of functional limitation or extra-articular disease.
- Patients must have:
> 4 tender joints (TJC) count (28 joint count) at screening and
> 4 swollen joint (SJC) count (28 joint count) at screening
Erythrocyte sedimentation rate (ESR) > 28 mm/hr OR hsCRP greater than ULN.
- Patient has been taking at least one and up to 3 synthetic oral DMARDS as combination therapy for at least 6 months, of which the 8 weeks preceding enrollment were at stable dose and route of administration between 15 and 25 mg/week for MTX, and the patient has not had adequate response as determined by the investigator and findings as specified above.
- Women of child bearing potential must use effective contraception.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion criteria:
- Use of more than 3 synthetic oral DMARDs.
- Prior use of anti-TNF or other biologic for treatment of rheumatoid arthritis at any point prior to screening.
- Other investigational therapy received within 8 weeks or five half-lives (whichever is longer) prior to Screening or any prior regenerative therapy treatments (including participation in any stem cell or regenerative medicine study)
- Pregnant or breast-feeding.
- Autoimmune disease other than RA
- History of or current inflammatory joint disease other than RA.
- Bedridden or confined to a wheelchair or patients who have had > 3 arthroplasties due to RA.
- Known hypersensitivity to dimethyl sulfoxide (DMSO), murine or bovine protein.
- Prior treatment with any cell-depleting therapies including investigational agents.
- Gold compounds if less than 8 weeks prior to randomization; immunoadsorption columns if less than 6 months prior to baseline.
- QTc = 450 ms for males and QTc = 470 ms for females at Screening.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
MedDRA version: 16.0 Level: LLT Classification code 10003268 Term: Arthritis rheumatoid System Organ Class: 100000004859

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: Allogeneic Mesenchymal Precursor Cells
Pharmaceutical Form: Suspension for injection
Other descriptive name: ALLOGENEIC MESENCHYMAL PRECURSOR CELLS
Concentration unit: Munit million units
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: 1. To demonstrate the efficacy of a single intravenous infusion of allogeneic mesenchymal precursor cells (MPCs) compared to placebo at 12 weeks post-infusion with MPCs or placebo in the treatment of patients with active rheumatoid arthritis (RA) who have not previously received treatment with biologics.

2. To evaluate the long-term efficacy and safety of allogeneic mesenchymal precursor cells (MPCs) over the entire study duration in the treatment of patients with active rheumatoid arthritis (RA) who have not previously received treatment with biologics.

Exploratory Objective: To determine change from baseline of serum biomarkers: IL-1, -6, -17; TNFa, TGFß; osteocalcin, RANKL; MMP-1, -3, -9, TIMP-1, -2, -4 IFN-gamma, CD-206 monocytes (via flow cytometry) and FOXP3+ lymphocytes (via flow cytometry).

Main Objective: To evaluate the safety, tolerability and feasibility of a single intravenous (IV) infusion of allogeneic mesenchymal precursor cells (MPCs) compared to placebo at 12 weeks post-infusion in the treatment of patients with active rheumatoid arthritis (RA) who have not previously received treatment with biologics.

Primary end point(s): Primary objective
Safety will be assessed by:
-Adverse events/serious adverse events (“primary endpoint”)
- Vital signs (BP, HR, RR, SpO2, temperature)
- Physical examination
- Clinical laboratory tests (hematology, biochemistry, and urinalysis, flow cytometry Class I and Class II PRA % with specificity, antibovine and antimurine antibody analysis)
- Electrocardiogram (ECG)
- Pulmonary function tests (lung volumes, DLCO, spirometry (FEV1, FVC))
- Chest x-ray (CXR)

Timepoint(s) of evaluation of this end point: 12 weeks post study product infusion

Secondary Outcome(s)

Secondary end point(s): Secondary objectives
1. Efficacy will be assessed by:
- ACR20
- ACR50
- ACR70
- DAS28 (mean changes from baseline as measured using hsCRP)
- Mean changes from baseline in all components of the ACR core response criteria
- Remissions (as defined in the 2011 Joint Statement of the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR)1
- Joint erosion of hands and wrists assessed via x-ray
- Patient reported outcomes
- Short-Form Health Survey Version 2.0. (SF36v2)
- Health Assessment Questionnaire Disability Index (HAQ-DI) as part of the ACR core set of measures for response criteria

2. Safety will be assessed by:
-Adverse events/serious adverse events (“primary endpoint”)
- Vital signs (BP, HR, RR, SpO2, temperature)
- Physical examination
- Clinical laboratory tests (hematology, biochemistry, and urinalysis, flow cytometry Class I and Class II PRA % with specificity, antibovine and antimurine antibody analysis)
- Electrocardiogram (ECG)
- Pulmonary function tests (lung volumes, DLCO, spirometry (FEV1, FVC))
- Chest x-ray (CXR)

Exploratory objective
- smeasurement of serum biomarkers: IL-1, -6, -17; TNFa, TGFß; osteocalcin, RANKL; MMP-1, -3, -9, TIMP-1, -2, -4.

Timepoint(s) of evaluation of this end point: 1. Efficacy at 12 weeks post study product infusion
2. Efficacy and safety over entire duration of study
Exploratory: Various timepoints during study

Secondary ID(s)

MSB-RA002

2012-005674-61-EE

Source(s) of Monetary Support

Mesoblast, Inc