ART-I02 in Patients With Rheumatoid Arthritis With Inflamed Wrists

NCT03445715 | Unknown Phase 1 DMC

• 1 other identifier: ART-I02-001
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the safety and tolerability of a single intra-articular administration of ART-I02 (AAV5.NF-kB.IFN-β), a recombinant adeno-associated virus (AAV) type 5 vector in subjects with RA and active arthritis of a wrist.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Treatment emergent (serious) adverse events

  The number of and the number of patients with treatment emergent AEs will be reported by 1.treatment, MedDRA SOC and PT; 2. treatment, MedDRA SOC, PT and severity; 3.treatment, MedDRA SOC, PT and drug relatedness

  5 years

Secondary Outcomes (18)

• Change from baseline for clinical signs and symptoms of the target joint evaluated by the Composite Change Index (CCI)

  Baseline, week 1, week 2 , week 4, week 8, week 12, week 16, week 20 and week 24 post administration of ART-I02

• Change from baseline after single dose of ART-I02 on overall disease activity measured by DAS28, over 24 weeks.

  Baseline, week 24 post administration of ART-I02

• Change from baseline after single dose of ART-I02 on hand function measured by Grip strength measurement in the target and contralateral joint.

  Baseline, week 1, week 2 , week 4, week 8, week 12, week 16, week 20 and week 24 post administration of ART-I02

• Change from baseline after single dose of ART-I02 on hand function measured by VAS pain in the target and contralateral joint.

  Baseline, week 1, week 2 , week 4, week 8, week 12, week 16, week 20 and week 24 post administration of ART-I02

• Change from baseline after single dose of ART-I02 on hand function measured by VAS function in the target and contralateral joint.

  Baseline, week 1, week 2 , week 4, week 8, week 12, week 16, week 20 and week 24 post administration of ART-I02

Study Arms (3)

Cohort I

EXPERIMENTAL

Single intra-articular injection ART-I02: 2.4x10E12 vg / wrist joint

Genetic: ART-I02

Cohort II

EXPERIMENTAL

Single intra-articular injection of ART-I02: 2.4x10E13 vg / wrist joint

Genetic: ART-I02

Cohort III

EXPERIMENTAL

Single intra-articular injection in the wrist joint of ART-I02 Maximum Tolerated Dose (MTD) as assessed in cohorts I and II:

Genetic: ART-I02

Interventions

ART-I02 GENETIC

Single Intra-articular injection in the wrist joint

Also known as: Recombinant AAV type2/5 containing a hIFN-b gene

Cohort I; Cohort II; Cohort III

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with RA aged ≥18 years.
• 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.
• Inflammation of the target wrist due to active RA as confirmed by MRI, and the (symptoms of) inflammation is (are) not satisfactorily controlled by current best-standard therapy, and/or that the patient could benefit from better therapeutic efficacy, according to judgment of the investigator.
• Written informed consent, able and willing to comply with the requirements of the study protocol.
• 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.
• Females are not pregnant nor lactating.
• All male patients use effective contraception in combination with barrier contraception until three consecutive semen samples are negative for ART-I02 genomic DNA. All female patients of childbearing potential use effective contraception in combination with barrier contraception for the first three months after administration.

You may not qualify if:

• Known hypersensitivity to natural or recombinant hIFN-β, or to any excipients.
• Contra-indication for intra-articular treatment.
• Presence of neutralizing antibody (Nab) titers against adeno-associated virus type 5 (AAV5) and/or hIFN-β.
• Active infectious disease of any nature, including clinical active viral infections.
• Previous treatment with an AAV 5 vector.
• Poor functional status, defined as being bed-bound or wheelchair-bound.
• Intra-articular corticosteroid treatment within one month prior to administration of the study medication.
• Participation in an investigational drug or device study within 90 days prior to screening or more than 4 times per year.
• Positive for human immunodeficiency virus (HIV) infection, hepatitis C antibodies or hepatitis B surface antigen.
• Positive for anti-double-stranded DNA antibodies (dsDNA).
• History of liver function abnormality requiring treatment, drug induced liver injury, chronic liver disease, excessive alcohol consumption or chronic alcohol induced disease.
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2 x upper limit of normal (ULN), or bilirubin \> 2 x ULN. If a patient has AST or ALT \> 2 x ULN but \< 2.5 x ULN, re-assessment is allowed at the investigator's discretion.
• Severely impaired renal function (estimated glomerular filtration rate ≤ 30 mL/min according to the Cockcroft-Gault formula).
• Patient had a major surgery, donated or lost approximately 500 mL blood within 4 months prior to the screening visit
• Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude.

Sponsors & Collaborators

• Arthrogen: lead

Study Sites (1)

University of Calgary, Division of Rheumatology, Cumming School of Medicine

Calgary, AB T2N 4N1, Canada

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• William O Martin, PhD

  University Of Calagary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2018
• First Posted: February 26, 2018
• Study Start: January 3, 2018
• Primary Completion: September 1, 2019
• Study Completion: January 1, 2020
• Last Updated: November 14, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)