None listed
Conditions
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 trial will examine the safety, tolerability and preliminary efficacy of DEN-181 in Rheumatoid arthritis patients.
Interventions
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 follow
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.
Sponsors
Dendright Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
No
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.
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.
Outcome results
None listed