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Trial registered on ANZCTR


Registration number
ACTRN12610000373077
Ethics application status
Approved
Date submitted
26/11/2009
Date registered
10/05/2010
Date last updated
12/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
A dendritic cell vaccine to suppress the immune response to citrullinated antigen in rheumatoid arthritis
Scientific title
A phase I clinical trial to assess the safety and induction of antigen-specific tolerance of autologous modified dendritic cells exposed to citrullinated peptides (Rheumavax) in patients with rheumatoid arthritis
Secondary ID [1] 251693 0
nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid arthritis 252293 0
Condition category
Condition code
Musculoskeletal 252473 252473 0 0
Other muscular and skeletal disorders
Inflammatory and Immune System 252484 252484 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Autologous modified dendritic cells (DC) pulsed with a mixture of four citrullinated peptide antigens (cit-vimentin
447-455, cit-fibrinogen beta chain 433-441, cit-fibrinogen alpha chain 717-725, cit-collagen type II 1237-1249) designated “Rheumavax”, will be administered intradermally once to each group of 9 rheumatoid arthritis patients on usual disease modifying drugs in 2 progressive vaccine dose levels (total of 18 vaccinated subjects) in an escalating dose regimen.
Group 1: 1 million DC on day 1 of study
Group 2: 5 million DC on day 1 of study
Intervention code [1] 241610 0
Treatment: Drugs
Comparator / control treatment
Open label, control (active) group receives standard care i.e. usual disease modifying drugs for the control of rheumatoid arthritis (RA)
Control group
Active

Outcomes
Primary outcome [1] 253349 0
Clinical measures of safety:
Clinical evaluation and glucose monitoring
Timepoint [1] 253349 0
baseline, 1 week, monthly for 3 months, and a final evaluation after 6 months in patients and controls
Primary outcome [2] 258375 0
Laboratory measures of safety:
Full blood count, biochemical profile. Anti-nuclear antigen, extractable nuclear antigens, radioallergosorbent test (RAST) and fasting lipid profile
Timepoint [2] 258375 0
baseline, 1 week, monthly for 3 months, and a final evaluation after 6 months in patients and controls. For autoantibodies, RAST and lipids: baseline and 6 months.
Primary outcome [3] 258376 0
Tolerance:
Reduction in anti-cyclic citrullinated peptide (CCP) antibody titre and rheumatoid factor titre by analysis of serum. Change in T cell subsets, proliferative and cytokine response in vitro to citrullinated-peptide by analysis of peripheral blood cells. Change in serum cytokine.
Timepoint [3] 258376 0
baseline, monthly for 3 months, and a final evaluation after 6 months in patients and controls
Secondary outcome [1] 262425 0
Clinical measures of efficacy:
Reduction in health assessment questionnaire score, disease activity score. American College of Rheumatology response score, and lack of progression of hand radiographs.
Timepoint [1] 262425 0
baseline, monthly for 3 months, and a final evaluation after 6 months in patients and controls. baseline and 6 months for radiographs.

Eligibility
Key inclusion criteria
1. Age 18-75 years
2. Either sex. It is anticipated that the male: female ratio will be approximately 4:6 for due to the female preponderance with Rheumatoid Arthritis (RA)
3. Subjects who are willing and able to participate in the study for 6 months and from whom written informed consent has been obtained.
4. Diagnosis of definite RA by American College of Rheumatology criteria with symptoms for at least 3 months
5. In female patients of child-bearing potential, safe contraceptive measures must be used
6. Blood glucose, routine hematology, creatinine, bilirubin and liver function tests within normal limits at entry
7. Must be receiving <10mg/day of prednisone as part of their drug treatment. Patients must have had RA diagnosed and treated by a rheumatologist. Acceptable disease modifying treatment (either as monotherapy or combination therapy) includes methotrexate, salazopyrin, hydroxychloroquine, gold injections, leflunomide, or biologics (etanercept, infliximab, humira or anakinra). Anti-inflammatory medications and local corticosteroid injections are also permissible.
8. Demonstrated anti-CCP antibodies. Rheumatoid factor positive or negative. human leukocyte antigen (HLA)-DR shared epitope positive (HLA-DRB1*0401, 0404, 0405, 0408, 01, 1001, 1401, 1402, 09)
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any malignancy
2. History or family history of atopy: eczema, asthma, nasal polyps or allergic rhinitis
3. Positive allergen reactivity (RAST) test
4. Serious infection within the past 28 days that has not adequately responded to therapy
5. Receipt of any live attenuated vaccines within 4 weeks of study entry.
6. Major surgery within the past 28 days
7. Significant cardiovascular, renal, liver, neurological or skin disease
8. Females who are pregnant or lactating or who expect to become pregnant within the duration of the study, or who refuse to take contraceptives for the duration of the study
9. Positive serology for Human Immunodeficiency virus (HIV), Hepatitis B virus (HBV), or Hepatitis C virus (HCV)
10. >10 mg prednisone daily
11. Treatment with cytotoxic or immunomodulatory therapies such as radiotherapy, cyclophosphamide, mycophenolate, tacrolimus, psoralen ultraviolet therapy (PUVA), etretinate, cyclosporine, or azathioprine.
12. History of drug abuse that would interfere with the ability to comply with the study protocol.
13. Any condition judged by the physician to cause this study to be detrimental to the patient.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
10/11/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 256090 0
Government body
Name [1] 256090 0
National Health and Medical Research Council (NHMRC)
Country [1] 256090 0
Australia
Primary sponsor type
University
Name
Uniquest
Address
The University of Queensland
Brisbane QLD 4072
Country
Australia
Secondary sponsor category [1] 251433 0
Hospital
Name [1] 251433 0
Princess Alexandra Hospital
Address [1] 251433 0
199 Ipswich Rd
Buranda Queensland 4102
Country [1] 251433 0
Australia

Ethics approval
Ethics application status
Approved

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30553 0
Address 30553 0
Country 30553 0
Phone 30553 0
Fax 30553 0
Email 30553 0
Contact person for public queries
Name 13800 0
Sr Helen Pahao
Address 13800 0
Diamantina Institute for Cancer, Immunology and Metabolic Medicine (DI)
University of Queensland
Level 4, R-wing, Building 1
Princess Alexandra Hospital
Brisbane 4102
Qld
Country 13800 0
Australia
Phone 13800 0
+61 7 32402170
Fax 13800 0
Email 13800 0
[email protected]
Contact person for scientific queries
Name 4728 0
Prof Ranjeny Thomas
Address 4728 0
Diamantina Institute for Cancer, Immunology and Metabolic Medicine (DI)
University of Queensland
Level 4, R-wing, Building 1
Princess Alexandra Hospital
Brisbane 4102
Qld
Country 4728 0
Australia
Phone 4728 0
+61 7 3240 5365
Fax 4728 0
Email 4728 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Benham H*, Nel HJ*, Law SC*, Mehdi AM*, Street S, ... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseAntigen-specific therapeutic approaches for autoimmunity.2019https://dx.doi.org/10.1038/s41587-019-0015-4
EmbaseThree distinct tolerogenic CD14+ myeloid cell types to actively manage autoimmune disease: Opportunities and challenges.2021https://dx.doi.org/10.1016/j.jaut.2021.102645
N.B. These documents automatically identified may not have been verified by the study sponsor.