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Trial registered on ANZCTR


Registration number
ACTRN12617001470381
Ethics application status
Approved
Date submitted
3/10/2017
Date registered
18/10/2017
Date last updated
16/09/2022
Date data sharing statement initially provided
16/09/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A clinical study to investigate the safety of multiple doses of DEN-181 in rheumatoid arthritis patients
Scientific title
A Phase I, randomised, double-blind, placebo-controlled, single centre, multiple-dose ranging 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] 293008 0
DEN-17-01-RA
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 304921 0
Condition category
Condition code
Inflammatory and Immune System 304251 304251 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Randomised double blind, placebo-controlled, single centre,study of three administrations of DEN-181 at two dose levels (15 active, 5 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).
Dose levels will be selected from 100µL, 300uL, or 1000µL DEN-181 and chosen following the single dose arm of this study. DEN-181 will be delivered by subcutaneous injection at weekly intervals for three weeks.
Intervention code [1] 299249 0
Treatment: Drugs
Comparator / control treatment
The study is placebo controlled. The placebo is normal saline (0.9% Sodium Chloride).
Control group
Placebo

Outcomes
Primary outcome [1] 303536 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] 303536 0
For the 56 day study period.
Assessment of primary outcomes will be conducted Day 1, 8 , 15 and 29 and at day 57 (exit evaluation).
Secondary outcome [1] 339220 0
Proportion and total number of naïve, effector and regulatory T-cells by flow cytometry (composite outcome).
Timepoint [1] 339220 0
Assessment of the proportion and total number of naïve, effector and regulatory T-cells will be conducted on study day 1, 8, and 29.
Secondary outcome [2] 339518 0
Determination of the concentration of calcitriol in plasma samples.
Timepoint [2] 339518 0
Assessment of plasma calcitrol concentration will be conducted on day 1, 8 and 15.
Secondary outcome [3] 339519 0
Mean changes in DAS28CRPv4 (Disease Activity Score 28 including CRP assessment 4 variable calculation) scoring system.
Timepoint [3] 339519 0
Assessment of changes in DAS28CRPv4 scoring system will be conducted on day 1, 8, 15, 29, 57.
Secondary outcome [4] 339839 0
Phenotype of naïve, effector and regulatory T-cells by flow cytometry.
Timepoint [4] 339839 0
Assessment of the phenotype of naïve, effector and regulatory T-cells will be conducted on study day 1, 8, and 29.

Eligibility
Key inclusion criteria
Diagnosis of RA made by a rheumatologist;
HLA-DRB1*0401+, HLA-DRB1*0101+ or HLA-DRB1*0401+HLADRB1*0101+ heterozygotes, homozygotes or compound heterozygotes and ACPA+;
Treatment with MTX at the same dose for at least 4 weeks prior to planned start of trial treatment;
Age 18-75 years, inclusive;
Male or female. Females of child-bearing potential must agree to use two effective forms of contraception from enrolment to completion of the study;
Patients must be informed of the investigational nature of this study and give written informed consent in accordance with the institutional and hospital guidelines;
Blood glucose, CBC, haemoglobin, platelets, creatinine, bilirubin, and AST/ALT not greater than 1.5 x out of normal laboratory ranges at entry and clinically insignificant in opinion of investigator;
Patients agree to forego vaccinations during the course of the study.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Malignancy;
An active inflammatory disease other than RA;
Currently receiving or have received treatment with >10mg prednisone daily within the last 2 weeks prior to screening;
Current or recent treatment (< 2 weeks prior) with any diseasemodifying anti-rheumatic drugs (DMARDS) other than MTX;
Serious infection requiring hospitalisation within last 28 days;
Receipt of any live attenuated vaccines within 4 weeks prior to entry;
Major surgery within last 28 days;
Significant cardiovascular, renal, liver, neurological or skin disease;
Positive serology for HIV, or infection with HBV or HCV;
Current treatment with cytotoxic or immunomodulatory therapies such as radiotherapy, cyclophosphamide, mycophenolate, tacrolimus, PUVA, acitretin cyclosporine or azathioprine;
Any known or suspected allergies to the study drug or its constituents including egg products;
Inadequate venous access to allow collection of blood samples;
History of drug or alcohol abuse;
Participation in any other clinical trial;
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)
The pharmacist or responsible party will prepare the treatment corresponding to the subject number in the randomisation plan.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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
Withdrawn
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Date of first participant enrolment
Anticipated
30/06/2018
Actual
Date of last participant enrolment
Anticipated
30/03/2019
Actual
Date of last data collection
Anticipated
26/08/2019
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 9129 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 17636 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 297636 0
Commercial sector/Industry
Name [1] 297636 0
Dendright Pty Ltd
Country [1] 297636 0
Australia
Funding source category [2] 297666 0
Charities/Societies/Foundations
Name [2] 297666 0
Arthritis Queensland
Country [2] 297666 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Dendright Pty Ltd
Address
Translational Research Institute
37 Kent St
Woolloongabba, Qld, 4102
Country
Australia
Secondary sponsor category [1] 296655 0
None
Name [1] 296655 0
Address [1] 296655 0
Country [1] 296655 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298723 0
Metro South Health Human Research Ethics Committee
Ethics committee address [1] 298723 0
Ethics committee country [1] 298723 0
Australia
Date submitted for ethics approval [1] 298723 0
13/07/2017
Approval date [1] 298723 0
31/08/2017
Ethics approval number [1] 298723 0
482

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

Contacts
Principal investigator
Name 78018 0
Dr Phillip Vecchio
Address 78018 0
Department Head of Rheumatology
Princess Alexandra Hospital
Ipswich Road
Woolloongabba, 4102 AUSTRALIA
Country 78018 0
Australia
Phone 78018 0
+61 7 3391 7500
Fax 78018 0
+61 7 3176 7131
Email 78018 0
phillip.vecchio@health.qld.gov.au
Contact person for public queries
Name 78019 0
Joanna Tesiram
Address 78019 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 78019 0
Australia
Phone 78019 0
+61 7 3176 2163
Fax 78019 0
+61 7 3240 7131
Email 78019 0
Joanne.Tesiram@health.qld.gov.au
Contact person for scientific queries
Name 78020 0
Helen Roberts
Address 78020 0
CEO
Dendright Pty Ltd
6NE.6006 Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Country 78020 0
Australia
Phone 78020 0
+61 (0) 419 657 504
Fax 78020 0
Email 78020 0
helen.roberts@uq.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.