A Single Dose Clinical Trial to Study the Safety of ART-I02 in Patients With Arthritis

NCT02727764 | Unknown Phase 1 DMC

• 1 other identifier: ART-I02-001-NL
• Study Type: interventional
• Target: 12
• 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 2/5 vector in subjects with Rheumatoid Arthritis (RA) or Osteoarthritis (OA) and active arthritis of the carpometacarpal (CMC), metacarpophalangeal (MCP), proximal interphalangeal (PIP), or distal interphalangeal (DIP) joints.

Conditions

Arthritis, Rheumatoid; Osteo Arthritis

Keywords

Arthritis; Gene therapy; Phase Ib; Intra-articular

Outcome Measures

Primary Outcomes (1)

• Treatment emergent (serious) adverse events

  Treatment emergent (serious) adverse events

  Five years

Secondary Outcomes (8)

• Change from baseline for clinical signs and symptoms of the target joint evaluated by the Composite Change Index (CCI) at week 1, week 2, week 4, week 8, week 12, week 16, week 20 and week 24 post administration of ART-I02.

  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 on synovitis and osteitis in the injected joint (target joint) evaluated by Magnetic Resonance Imaging (MRI) 12 and 24 weeks after administration of ART-I02 using the OMERACT RA MRI scoring system (RAMRIS).

  12 and 24 weeks after administration of ART-I02

• Vector DNA in whole peripheral blood, semen, urine, feces, and saliva

  Up to 24 weeks but maximally until such time that three consecutive samples have been tested negative

• Induction of humoral immune responses against AAV5 by measuring antibodies against AAV5 and neutralizing antibodies against AAV5 at baseline, week 4 and week 24 post administration

  Baseline, week 4 and week 24 post administration

• Induction of humoral immune responses against hIFN-β by measuring antibodies against IFN-β and neutralizing antibodies against hIFN-β at baseline, week 4 and week 24 post administration

  Baseline, week 4 and week 24 post administration

Study Arms (3)

Cohort I

EXPERIMENTAL

ART-I02 1.2x10e12 vg/ CMC joint, 1.2x10e12 vg/ MCP joint, 0.6x10e12 vg/ PIP joint or 0.3x10e12 vg/ DIP joint single intra-articular injection

Genetic: ART-I02

Cohort II

EXPERIMENTAL

ART-I02 1.2x10e12 vg/ CMC joint, 1.2x10e13 vg/ MCP joint, 0.6x10e13 vg/ PIP joint or 0.3x10e13 vg/ DIP joint single intra-articular injection

Genetic: ART-I02

Cohort III

EXPERIMENTAL

ART-I02 1.2x10e12 vg/ CMC joint, 1.2x10e13 vg/ MCP joint, 0.6x10e13 vg/ PIP joint or 0.3x10e13 vg/ DIP joint ART-I02 or maximum Tolerated Dose (MTD) as assessed in cohorts I and II: single intra-articular injection

Genetic: ART-I02

Interventions

ART-I02 GENETIC

Single Intra-articular injection in the carpometacarpal (CMC), metacarpophalangeal (MCP), proximal interphalangeal (PIP), or distal interphalangeal (DIP) 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 ≥18 years of age.
• Patient have to be 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 B or OA as confirmed by their treating physician/specialist.
• Patient is scheduled for surgical intervention of the target joint.
• Inflammation of the CMC, MCP, PIP or DIP joint as confirmed by MRI.
• 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 patients use effective contraception in combination with barrier contraception for the first three months after administration or until three consecutive semen samples are negative.

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 neutralising 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.
• 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 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
• 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 patient unsuitable for the study.

Sponsors & Collaborators

• Arthrogen: lead
• Centre for Human Drug Research (CHDR): collaborator

Study Sites (1)

Centre for Human Drug Research (CHDR)

Leiden, South Holland, Netherlands

Location

Related Publications (1)

• Vrouwe JPM, Meulenberg JJM, Klarenbeek NB, Navas-Canete A, Reijnierse M, Ruiterkamp G, Bevaart L, Lamers RJ, Kloppenburg M, Nelissen RGHH, Huizinga TWJ, Burggraaf J, Kamerling IMC. Administration of an adeno-associated viral vector expressing interferon-beta in patients with inflammatory hand arthritis, results of a phase I/II study. Osteoarthritis Cartilage. 2022 Jan;30(1):52-60. doi: 10.1016/j.joca.2021.09.013. Epub 2021 Oct 6.

  PMID: 34626797 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid; Arthritis

Condition Hierarchy (Ancestors)

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

Study Officials

• Koos Burggraaf, PhD

  Principal Investigator

  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: March 9, 2016
• First Posted: April 5, 2016
• Study Start: April 20, 2017
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: November 14, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)