Autologous Tolerogenic Dendritic Cells for Rheumatoid Arthritis (AutoDECRA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by Newcastle University
Sponsor:
Collaborators:
Arthritis Research UK
Newcastle-upon-Tyne Hospitals NHS Trust
Information provided by (Responsible Party):
Newcastle University
ClinicalTrials.gov Identifier:
NCT01352858
First received: May 11, 2011
Last updated: March 10, 2013
Last verified: March 2013
  Purpose

This is a study which will look at safety, feasibility and acceptability of a new therapy called tolerogenic dendritic cells (TolDC), derived from the patient's own white blood cells, which will be injected into the knee joints of rheumatoid arthritis patients, using a procedure called arthroscopy (a camera examination of a joint). The investigators are also looking to see if the drug has any effect on the disease activity (if it can help in RA) and whether the drug can affect the immune system. The investigators aim to treat 12 patients in total, 9 with TolDC and 3 with a control treatment. Three doses of TolDC will be tested, 3 patients per dose. Subjects will have RA and at least one swollen knee joint. They will undergo a knee ultrasound scan, fill in a series of questionnaires, have their knee aspirated (fluid taken out) and finally undergo a procedure called leukapheresis (removal of white blood cells) from which the treatment will be manufactured. Subsequently they will undergo 3 arthroscopies (camera examination of the knee joint) over a period of about 12 weeks. On the first arthroscopy they will have the TolDC injected into their knee joint. They will then spend the night at the Clinical Research facility for observation. Over the next 5 days they will be telephoned daily by the study doctor to check how they are, and will be reassessed if needed. About 2 weeks later they will have their second arthroscopy to look for effects of treatment, and the third will take place at 13 weeks (end of study) or sooner if the knee appears to get worse.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: TolDC
Drug: Arthroscopy & saline irrigation alone
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Phase 1 Study of Autologous Tolerogenic Dendritic Cells for Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Newcastle University:

Primary Outcome Measures:
  • The proportion of patients experiencing AEs and SAEs following the intra-articular administration of TolDC. [ Time Frame: within 3 months of injection ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • • The proportion of RA patients who enter the study, from whom GMP-grade TolDC of sufficient quality can be prepared (the success rate of the TolDC preparation procedure). [ Time Frame: Within one week of donation of blood for extraction of TolDC ] [ Designated as safety issue: No ]
  • • The proportion of patients who grade the trial and its related procedures as acceptable. [ Time Frame: At final study visit, 3 months after study intervention. ] [ Designated as safety issue: No ]
    Trial participants will assess acceptability of study specific procedures via an 'acceptability questionnaire' administered at the last study visit

  • Systemic RA disease activity [ Time Frame: At baseline and at 7, 14 and 91 days post intervention ] [ Designated as safety issue: No ]
    Disease Activity Score using 28 joints (DAS28)

  • Knee function [ Time Frame: At baseline and at 7, 14 and 91 days post-intervention ] [ Designated as safety issue: No ]
    Function will be assessed using the Health Assessment Questionnaire (HAQ), a standard instrument used in RA


Estimated Enrollment: 12
Study Start Date: February 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TolDC
Experimental arm - TolDC administered arthroscopically
Drug: TolDC
Tolerogenic dendritic cells (TolDC), derived ex vivo from autologous monocytes, administered arthroscopically into an inflamed knee following saline irrigation.
Placebo Comparator: Control
Arthroscopy & saline irrigation alone
Drug: Arthroscopy & saline irrigation alone

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Able and willing to give informed consent and to comply with the study protocol
  • At least 6 month's disease duration
  • ACR Functional Class I-III
  • Age 18 years or over
  • Active disease, including an inflamed (native) knee joint
  • Failure (or intolerance of) at least one disease modifying anti-rheumatic drug (DMARD), including current therapy
  • Morning stiffness in the target joint ≥ 30 minutes
  • Willing and able to undergo arthroscopic procedures under local anaesthetic
  • Stable dose of non-steroidal anti-inflammatory drug (NSAID) or corticosteroid (prednisolone≤10mg) for ≥4 weeks
  • No intramuscular glucocorticoid administration for ≥ 6 weeks
  • Stable dose of disease-modifying anti-rheumatic drug (DMARD) for ≥8 weeks

Exclusion Criteria:

  • Use of other investigational medicinal products within 30 days prior to study entry (defined as date of recruitment into study)
  • Patients who have received rituximab therapy and whose B-cell count remains below the normal range. Patients who have received any other cell depleting therapies and whose cell counts have not returned to the normal range, at the discretion of the principal investigator.
  • Serious or unstable co-morbidity deemed unsuitable by PI, eg. COPD, cardiac failure
  • History of malignancy (except treated basal cell carcinoma of skin)
  • Known active infection at screening visit or at baseline (except fungal nail infection)
  • Infection requiring hospitalization or IV antibiotics within 6 weeks of baseline
  • Immunization with live vaccine within 6 weeks of baseline
  • History of recurrent or chronic infection
  • History of hepatitis B or C, syphilis, HIV or HTLV-1/2 infections
  • Injection of target joint with glucocorticoids within 6 weeks of baseline
  • Hb<10g/dL; neutrophils< 2.00 x109/L; platelets <150x109/L; ALT/ALP>2x upper limit of normal; elevated serum creatinine at screening visit.
  • Major surgery within 8 weeks of baseline or planned within 3 months from baseline
  • Pregnancy, or women planning to become pregnant within the study period, or women who are breast feeding
  • Females or males of child bearing potential unwilling to use adequate contraception for duration of study
  • Patients taking anticoagulants
  • Known hypersensitivity to local or systemic corticosteroid therapy or local anaesthetic.
  • Poor venous access or medical condition precluding leukapheresis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01352858

Contacts
Contact: John D Isaacs, PhD +441912225337 j.d.isaacs@ncl.ac.uk
Contact: Gillian M Bell, MBBS +441912225337 g.m.bell@ncl.ac.uk

Locations
United Kingdom
Newcastle University Recruiting
Newcastle upon Tyne, United Kingdom, NE2 4HH
Principal Investigator: John D Isaacs, PhD         
Sub-Investigator: Gillian M Bell, MBBS         
Sponsors and Collaborators
Newcastle University
Arthritis Research UK
Newcastle-upon-Tyne Hospitals NHS Trust
  More Information

No publications provided

Responsible Party: Newcastle University
ClinicalTrials.gov Identifier: NCT01352858     History of Changes
Other Study ID Numbers: AutoDECRA 1.0
Study First Received: May 11, 2011
Last Updated: March 10, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Newcastle University:
Arthritis
RA
Auto-immune disorders

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on August 27, 2014