A single dose clinical trial to study the safety of ART-I02 in patients with rheumatoid arthritis

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 15

Inclusion Criteria

Eligible subjects must meet all of the following inclusion criteria at screening:;1. Female subjects (age *18 years) must be post-menopausal for at least one year (defined as amenorrhea * 12 consecutive months without another cause, and confirmed by follicle stimulating hormone level > 35 mIU/mL)
2. Patient has been diagnosed with RA according to the 2010 American College of Rheumatology/ European league against rheumatism (ACR/EULAR) criteria for the classification of RA, outlined in appendix A.
3. Inflammation of the target wrist due to active RA as confirmed by MRI.
4. Written informed consent, able and willing to comply with the requirements of the study protocol.
5. Judged to be in general good health with, in the opinion of the investigator, no other clinically significant and relevant abnormalities of medical history, and no abnormalities at the physical examination, vital signs, electrocardiography (ECG) and laboratory safety tests, performed at the screening visit and/or prior to administration of ART-I02.

Exclusion Criteria

Eligible subjects must meet none of the following exclusion criteria at screening:;1. Arthrodesis or joint replacement of the target wrist prior to inclusion.
2. Known hypersensitivity to natural or recombinant hIFN-*, or to any excipients.
3. Contra-indication for intra-articular treatment.
4. Presence of neutralizing antibody (Nab) titers against adeno-associated virus type 5 (AAV5) and/or hIFN-*.
5. Active infectious disease of any nature, including clinical active viral infections.
6. Previous treatment with an AAV 5 vector.
7. Oral corticosteroid therapy at doses higher than the equivalent of 10 mg prednisone per day within 4 weeks prior to administration of the study medication.
8. Intra-articular or parenteral corticosteroid treatment within one month prior to the administration of the study medication.
9. Current use of a Tumor Necrosis Factor alpha antagonist (TNF-* antagonist), (including etanercept, certolizumab, adalimumab, infliximab, golimumab) or anakinra, and other biological agents including abatacept, tocilizumab and rituximab.
10. Poor functional status, defined as being bed-bound or wheelchair-bound.
11. Participation in an investigational drug or device study within 90 days prior to screening or more than 4 times per year.
12. Positive for human immunodeficiency virus (HIV) infection, hepatitis C antibodies or hepatitis B surface antigen.
13. Positive for anti-double-stranded DNA antibodies (dsDNA).
14. History of liver function abnormality requiring treatment, drug induced liver injury, chronic liver disease, excessive alcohol consumption or chronic alcohol induced disease.
15. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 x upper limit of normal (ULN), or bilirubin 2 x ULN. If a subject has AST or ALT > 2 x ULN but < 2.5 x ULN, re-assessment is allowed at the investigator*s discretion.
16. Severely impaired renal function (estimated glomerular filtration rate * 30 mL/min according to the Cockcroft-Gault formula).
17. Subject had a major surgery, donated or lost approximately 500 mL blood within 4 months prior to the screening visit
18. Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude
19. Serious medical disease, such as severe liver or kidney disease, uncompensated congestive heart failure, myocardial infarction within six months, unstable angina, uncontrolled hypertension, severe pulmonary disease or active asthma, demyelinating neurological disease, depression or a history of depression, history of seizures or epilepsy, uncontrolled epilepsy, or history of cancer (other than cutaneous basal and squamous cell carcinoma or cervical intraepithelial neoplasia) with less than five years documentation of a disease-free state, recurrent opportunistic infections or other concurrent medical condition that, in the opinion of the investigator, would make the subject unsuitable for the study.
20. Investigator has concerns regarding the safe participation of the subject in the trial or for any other reasons: the investigator considers the subject inappropriate for participation in the trial.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoints are safety and tolerability, as assessed by<br /><br>1. treatment emergent (serious) adverse events<br /><br>2. concomitant medication<br /><br>3. clinical laboratory tests<br /><br>a. haematology<br /><br>b. chemistry<br /><br>c. urinalysis<br /><br>4. vital signs<br /><br>a. pulse rate<br /><br>b. systolic blood pressure<br /><br>c. diastolic blood pressure<br /><br>d. body temperature<br /><br>5. ECG parameters<br /><br>a. HR, PR, QRS, QT and Qtc</p><br>

Secondary Outcome Measures