Clinical trial NCT03161457: A Study of JHL1101 Versus MabThera® in Subjects With Severe Rheumatoid Arthritis
Official title: A Randomised, Double-blind, Parallel Group, Multicentre Study to Compare the Pharmacokinetics, Pharmacodynamics, Immunogenicity, Safety, and Efficacy of JHL1101 Versus EU-sourced MabThera® in Anti TNF Inadequate Responder Patients With Moderate to Severe Rheumatoid Arthritis (RA) on Background Methotrexate (MTX) Therapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Arthritis, Rheumatoid
Keywords: RA
Moderate RA
Moderate Rheumatoid Arthritis
Severe RA
Severe Rheumatoid Arthritis
Moderate to Severe RA
Moderate to Severe Rheumatoid Arthritis
Lead sponsor: JHL Biotech, Inc.
Sponsor class: INDUSTRY
First posted: 2017-05-19
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicentre, randomised, double-blind, parallel group study to compare the pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, safety, tolerability and efficacy of JHL1101 versus MabThera in subjects with moderate to severe RA who have previously failed at least 1 tumour necrosis factor alpha (TNF) inhibitor (i.e., intolerance or documented active disease despite at least 12 weeks treatment according to the TNF inhibitor-approved treatment and dosage), and are on concomitant treatment with MTX.

Detailed description: This study will take place across approximately 31 centres across 12 countries and will randomise approximately 150 subjects as outpatients.

The primary objective is to investigate and compare the pharmacokinetic profiles of JHL1101 and MabThera (rituximab). The secondary objectives are to investigate the safety, tolerability, and immunogenicity of JHL1101 versus MabThera, to investigate the pharmacodynamics profile of JHL1101 versus MabThera, and investigate the efficacy of JHL1101 versus MabThera.

Eligibility criteria: Inclusion Criteria:

* Moderate to severe active RA
* Documented intolerance to or inadequate response to at least 12 weeks of treatment with the licensed regimen of at least one TNF inhibitor therapy
* Women of childbearing potential must use a medically acceptable means of birth control and agree to continue its use during the study and for at least twelve months after the last dose of study drug.

Exclusion Criteria:

* History of a severe allergic reaction or anaphylactic reaction to a biological agent or history of hypersensitivity to any component of the study drug including known hypersensitivity or allergy to a murine product
* Class IV as per the Classification of Global Functional Status in Rheumatoid Arthritis or wheelchair/bed-bound
* Have any significant systemic involvement with RA such as vasculitis, pulmonary fibrosis or Felty's syndrome
* History of or current inflammatory joint disease other than RA or other systemic disorder where the treatment or current or potential symptoms could confound the assessment of RA, with the exception of secondary Sjögren's syndrome
* Concomitant or recent DMARD treatments for RA
* Oral corticosteroids \>10mg/day prednisone equivalent or dose which has not been stable for the 4 weeks prior to Baseline
* Receipt of an intra-articular or other injectable corticosteroid within 4 weeks prior to Screening
* Intolerance or contraindications to IV corticosteroids
* Use of NSAIDs which have not been at a stable dose within 2 weeks prior to Baseline.
* Have undergone surgical treatments for RA including synovectomy and arthroplasty in more than 3 joints and/or within the last 8 weeks prior to Screening
* History of major surgery within the 12 weeks prior to Screening
* History of an infected joint prosthesis which subsequently has not been surgically removed/replaced
* Positive serological test for HBsAg, hepatitis B core antibody or hepatitis C serology.
* History of HIV infection, or a positive test at Screening
* History of tuberculosis (TB) infection.
* Acute clinical manifestations of herpes zoster virus or herpes simplex.
* Active infection of any kind or any major episode of infection requiring hospitalization within 24 week prior to Baseline or requiring treatment with IV anti-infective agents within 8 weeks prior to Baseline or oral anti infective agents within 2 weeks prior to Baseline
* Subjects at risk of progressive multifocal leukoencephalopathy (PML) as per protocol
* Any significant cardiac disease
* Subjects with a history of solid-organ transplantation
* History of lympho- or myeloproliferative disorder or malignancy within the last 5 years

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Area under plasma concentration versus time curve (AUC)
timeFrame: Day 0 through Week 52
measure: Trough Concentration
timeFrame: Day 15
measure: Maximum Concentration (Cmax)
timeFrame: Day 15
Secondary outcomes:
measure: AUC
timeFrame: Up to Week 12
measure: Time to maximum plasma concentration
timeFrame: Day 0 through Week 52
measure: Cmax
timeFrame: Day 0 through Week 52
measure: Total body clearance
timeFrame: Day 0 through Week 52
measure: Volume of distribution
timeFrame: Day 0 through Week 52
measure: Terminal half life
timeFrame: Day 0 through Week 52
measure: Area under plasma concentration versus time curve
timeFrame: Week 2 to Week 24
measure: Incidence of treatment-related adverse events (safety)
timeFrame: Until End-of-Study follow-up at Week 52
measure: Immunogenicity
timeFrame: Baseline, Weeks 12, 16, 24, and 52
measure: Area under the depletion-time curve of CD19+ B-cell
timeFrame: Day 0 to Day 15, Day 0 to Week 12, Day 0 to Week 24, and Day 0 to Week 52 (end of study)
measure: Change from Baseline in CD4+ T-cell counts
timeFrame: Day 0 through Week 52
measure: American College of Rheumatology (ACR) criteria 20, 50, 70 response rate
timeFrame: Weeks 4, 8, 12, 16, 24 and 52 and over time from Baseline to Week 52
measure: Swollen and tender joint count
timeFrame: From Baseline to Week 52
measure: Subject's assessment of arthritis pain
timeFrame: From Baseline to Week 52
Other outcomes:
Locations:
city: Banja Luka
country: Bosnia and Herzegovina
facility: JHL Biotech Investigational Site
city: Bijeljina
country: Bosnia and Herzegovina
facility: JHL Biotech Investigational Site
city: Plovdiv
country: Bulgaria
facility: JHL Biotech Investigational Site
city: Sofia
country: Bulgaria
facility: JHL Biotech Investigational Site
city: Sofia
country: Bulgaria
facility: JHL Biotech Investigational Site
city: Praha
country: Czechia
facility: JHL Biotech Investigational Site
city: Bad Doberan
country: Germany
facility: JHL Biotech Investigational Site
city: Hildesheim
country: Germany
facility: JHL Biotech Investigational Site
city: Magdeburg
country: Germany
facility: JHL Biotech Investigational Site
city: Rendsburg
country: Germany
facility: JHL Biotech Investigational Site
city: Budapest
country: Hungary
facility: JHL Biotech Investigational Site
city: Vilnius
country: Lithuania
facility: JHL Biotech Investigational Site
city: Poznan
country: Poland
facility: JHL Biotech Investigational Site
city: Wroclaw
country: Poland
facility: JHL Biotech Investigational Site
city: Kazan'
country: Russian Federation
facility: JHL Biotech Investigational Site
city: Moscow
country: Russian Federation
facility: JHL Biotech Investigational Site
city: Moscow
country: Russian Federation
facility: JHL Biotech Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: JHL Biotech Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: JHL Biotech Investigational Site
city: Samara
country: Russian Federation
facility: JHL Biotech Investigational Site
city: Saratov
country: Russian Federation
facility: JHL Biotech Investigational Site
city: Yaroslavl'
country: Russian Federation
facility: JHL Biotech Investigational Site
city: Taichung
country: Taiwan
facility: JHL Biotech Investigational Site
city: Taipei
country: Taiwan
facility: JHL Biotech Investigational Site
city: Taipei
country: Taiwan
facility: JHL Biotech Investigational Site
city: Kharkiv
country: Ukraine
facility: JHL Biotech Investigational Site
city: Kyiv
country: Ukraine
facility: JHL Biotech Investigational Site
city: L'viv
country: Ukraine
facility: JHL Biotech Investigational Site
city: Poltava
country: Ukraine
facility: JHL Biotech Investigational Site
city: Vinnytsya
country: Ukraine
facility: JHL Biotech Investigational Site
city: London
country: United Kingdom
facility: JHL Biotech Investigational Site
city: Southampton
country: United Kingdom
facility: JHL Biotech Investigational Site
Study officials:
References: