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Trial registered on ANZCTR


Registration number
ACTRN12617001482358
Ethics application status
Approved
Date submitted
20/09/2017
Date registered
19/10/2017
Date last updated
15/03/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A clinical study to investigate the safety of DEN-181 in rheumatoid arthritis patients
Scientific title
A Phase I, randomised, double-blind, placebo-controlled, single centre, single-dose escalation study to investigate the safety, tolerability, and pharmacodynamics of subcutaneously administered DEN-181 in adult patients with ACPA+ rheumatoid arthritis on stable treatment with methotrexate.
Secondary ID [1] 292591 0
Dendright Pty Ltd
DEN-17-RA-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 304263 0
Condition category
Condition code
Inflammatory and Immune System 303613 303613 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Randomised double blind, placebo-controlled, single centre, single-dose escalation study of DEN-181 at three dose levels (4 active, 2 placebo per dose level).
DEN-181 is a liposomal formulation encapsulating two active pharmaceutical ingredients, calcitriol (0.6 ug/mL) and collagen II peptide (42 ug/mL; 15 amino acid peptide corresponding to collagen II protein 259-273 (Proline 273 Hydroxyproline substitution).
DEN-181 is given by subcutaneous injection at a volume of 100 uL, 300 uL or 1000 uL.

Intervention code [1] 298800 0
Treatment: Drugs
Comparator / control treatment
Study is placebo controlled. Placebo is sterile saline for injection (0.9% NaCl). Background therapy is methotrexate.
Control group
Placebo

Outcomes
Primary outcome [1] 302968 0
Clinical safety observations including changes in:
Vital signs,
Symptom directed physical examination,
Adverse events (graded according to Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03)),
Laboratory abnormalities (Haematology including ESR and Clinical chemistry including CRP in serum samples),
Urinalysis
Timepoint [1] 302968 0
For 56 days after administration of a single dose of DEN-181.
All primary safety assessments are to be performed on day 1, 8, 15, 29, 57.
Secondary outcome [1] 337590 0
Proportion and total number of naïve, effector and regulatory T-cells by flow cytometry (composite outcome)

Timepoint [1] 337590 0
Assessment of the proportion, total number and phenotype of naïve, effector and regulatory T-cells will be conducted on day Day 1, 8 and 29.
Secondary outcome [2] 339520 0
Determination of the concentration of calcitriol in plasma samples.
Timepoint [2] 339520 0
Assessment of plasma calcitriol will performed on day 1.
Secondary outcome [3] 339521 0
Mean changes in DAS28CRPv4 (Disease Activity Score 28 including CRP assessment 4 variable calculation) scoring system.
Timepoint [3] 339521 0
Assessment of DAS28CRPv4 score will be performed on day 1, 8, 15, 29, 57.
Secondary outcome [4] 339840 0
Phenotype of naïve, effector and regulatory T-cells by flow cytometry
Timepoint [4] 339840 0
Assessment of the phenotype of naïve, effector and regulatory T-cells will be conducted on day Day 1, 8 and 29.

Eligibility
Key inclusion criteria
The criteria for entry into the study are:
1. Diagnosis of rheumatoid arthritis made by a rheumatologist;
2. HLA-DRB1*0401+, HLA-DRB1*0101+ or HLA-DRB1*0401+HLA-DRB1*0101+ heterozygotes, homozygotes or compound heterozygotes; and ACPA+ (anti-CCP2>6);
3. Treatment with MTX at the same dose for at least 4 weeks prior to planned start of trial treatment;
4. Age 18-75 years (male or female) inclusive;
5. Patients must be informed of the investigational nature of this study and give voluntary written informed consent in accordance with the institutional and hospital guidelines;
6. With or without swollen joints;
7. Male or Female. Females of child-bearing potential must agree to use two effective forms of contraception from enrolment to completion of the study;
8. Blood glucose, CBC, haemoglobin, platelets, creatinine, bilirubin, and AST/ALT not greater than 1.5 times out of normal range at entry and clinically insignificant in the opinion of the investigator;
9. Patients agree to forego vaccinations during the course of the study;
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
The criteria for exclusion from the study are:
1. Malignancy;
2. An active inflammatory disease other than RA;
3. Currently receiving or have received treatment with >10mg prednisone daily within the last 2 weeks prior to screening;
4. Current or recent treatment (< 2 weeks prior) with any disease-modifying anti- rheumatic drugs other than methotrexate;
5. Serious infection requiring hospitalization within last 28 days;
6. Receipt of any live attenuated vaccines within 4 weeks prior to entry;
7. Major surgery within last 28 days;
8. Significant cardiovascular, renal, liver, neurological or skin disease;
9. Positive serology for HIV or infection with HBV or HCV;
10. Treatment with cytotoxic or immunomodulatory therapies such as radiotherapy, cyclophosphamide, mycophenolate, tacrolimus, PUVA, acitretin, cyclosporine or azathioprine;
11. Any known or suspected allergies to the study drug or its constituents including egg products;
12. Inadequate venous access to allow collection of blood samples;
13. History of drug or alcohol abuse;
14. Participation in another clinical study;
15. If, in the opinion of the PI, the subject appears not to be able to perform the needed responsibilities of participation in the clinical study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation.
A randomisation scheme will be prepared in advance by the study statistician using a computer generated system according to relevant SOPs.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
No formal sample size calculations were performed for this study.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 8689 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 16800 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 297169 0
Commercial sector/Industry
Name [1] 297169 0
Dendright Pty Ltd
Address [1] 297169 0
6NE.6006
Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Country [1] 297169 0
Australia
Funding source category [2] 297170 0
Charities/Societies/Foundations
Name [2] 297170 0
Arthritis Queensland
Address [2] 297170 0
1 Cartwright Street (Cnr Lutwyche Road)
WINDSOR QLD 4030
Country [2] 297170 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Dendright Pty Ltd
Address
6NE.6006
Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Country
Australia
Secondary sponsor category [1] 296188 0
None
Name [1] 296188 0
Address [1] 296188 0
Country [1] 296188 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298337 0
Metro South Health Human Research Ethics Committee
Ethics committee address [1] 298337 0
PAH Centres for Health Research
Level 7, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Ethics committee country [1] 298337 0
Australia
Date submitted for ethics approval [1] 298337 0
13/07/2017
Approval date [1] 298337 0
31/08/2017
Ethics approval number [1] 298337 0
482

Summary
Brief summary
Current treatments to control damaging immune responses during autoimmunity use broad immunosuppressive drugs associated with undesirable side effects. Alternative strategies to control damaging immune responses are desirable. DEN-181 offers a novel liposomal therapy that does not broadly suppress the immune system, with the associated increased risk of infectious complications, but rather is designed to specifically address the underlying pathology of Rheumatoid Arthritis by re-programming the immune system towards tolerance for improved patient outcomes and minimal side effects. This study is designed to assess the safety and tolerability of a single dose of DEN-181 in Rheumatoid Arthritis patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 76758 0
Dr Phillip Vecchio
Address 76758 0
Princess Alexandra Hospital
Ipswich Road
WOOLLOONGABBA, QLD, 4102
Country 76758 0
Australia
Phone 76758 0
+61 7 3391 7500
Fax 76758 0
+61 7 3176 7131
Email 76758 0
phillip.vecchio@health.qld.gov.au
Contact person for public queries
Name 76759 0
Ms Joanna Tesiram
Address 76759 0
Clinical Nurse - Biologics/Clinical Trials Coordinator/Clinical Research Nurse Rheumatology Unit |
Division of Medicine
Princess Alexandra Hospital
Metro South Health
199 Ipswich Road
Woolloongabba QLD 4102
Country 76759 0
Australia
Phone 76759 0
+61 7 3176 2163
Fax 76759 0
+61 7 3240 7131
Email 76759 0
Joanne.Tesiram@health.qld.gov.au
Contact person for scientific queries
Name 76760 0
Ms Helen Roberts
Address 76760 0
CEO
Dendright Pty Ltd
6NE.6006 Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Country 76760 0
Australia
Phone 76760 0
+61 (0) 419 657 504
Fax 76760 0
Email 76760 0
helen.roberts@uq.edu.au

No data has been provided for results reporting
Summary results
Not applicable