A Study of JHL1101 Versus MabThera® in Subjects With Severe Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03161457
• Other study ID #: JHL-CLIN-1101-01
• Status: Terminated
• Phase: Phase 1
• Start date: February 27, 2017
• Est. completion date: April 16, 2019

Study information

• Verified date: January 2020
• Source: JHL Biotech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 153
• Est. completion date: April 16, 2019
• Est. primary completion date: April 16, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• JHL1101
1000 mg containing 10 mg/mL rituximab to be diluted to a concentration of 1 to 4 mg/mL in 0.9% normal saline or 5% D-glucose for administration
• MabThera
1000 mg containing 10 mg/mL rituximab to be diluted to a concentration of 1 to 4 mg/mL in 0.9% normal saline or 5% D-glucose for administration

Locations

Country	Name	City	State
Bosnia and Herzegovina	JHL Biotech Investigational Site	Banja Luka
Bosnia and Herzegovina	JHL Biotech Investigational Site	Bijeljina
Bulgaria	JHL Biotech Investigational Site	Plovdiv
Bulgaria	JHL Biotech Investigational Site	Sofia
Bulgaria	JHL Biotech Investigational Site	Sofia
Czechia	JHL Biotech Investigational Site	Praha
Germany	JHL Biotech Investigational Site	Bad Doberan
Germany	JHL Biotech Investigational Site	Hildesheim
Germany	JHL Biotech Investigational Site	Magdeburg
Germany	JHL Biotech Investigational Site	Rendsburg
Hungary	JHL Biotech Investigational Site	Budapest
Lithuania	JHL Biotech Investigational Site	Vilnius
Poland	JHL Biotech Investigational Site	Poznan
Poland	JHL Biotech Investigational Site	Wroclaw
Russian Federation	JHL Biotech Investigational Site	Kazan'
Russian Federation	JHL Biotech Investigational Site	Moscow
Russian Federation	JHL Biotech Investigational Site	Moscow
Russian Federation	JHL Biotech Investigational Site	Saint Petersburg
Russian Federation	JHL Biotech Investigational Site	Saint Petersburg
Russian Federation	JHL Biotech Investigational Site	Samara
Russian Federation	JHL Biotech Investigational Site	Saratov
Russian Federation	JHL Biotech Investigational Site	Yaroslavl'
Taiwan	JHL Biotech Investigational Site	Taichung
Taiwan	JHL Biotech Investigational Site	Taipei
Taiwan	JHL Biotech Investigational Site	Taipei
Ukraine	JHL Biotech Investigational Site	Kharkiv
Ukraine	JHL Biotech Investigational Site	Kyiv
Ukraine	JHL Biotech Investigational Site	L'viv
Ukraine	JHL Biotech Investigational Site	Poltava
Ukraine	JHL Biotech Investigational Site	Vinnytsya
United Kingdom	JHL Biotech Investigational Site	London
United Kingdom	JHL Biotech Investigational Site	Southampton

Sponsors (1)

Lead Sponsor	Collaborator
JHL Biotech, Inc.

Countries where clinical trial is conducted

Bosnia and Herzegovina,  Bulgaria,  Czechia,  Germany,  Hungary,  Lithuania,  Poland,  Russian Federation,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under plasma concentration versus time curve (AUC)		Day 0 through Week 52
Primary	Trough Concentration		Day 15
Primary	Maximum Concentration (Cmax)		Day 15
Secondary	AUC		Up to Week 12
Secondary	Time to maximum plasma concentration		Day 0 through Week 52
Secondary	Cmax		Day 0 through Week 52
Secondary	Total body clearance		Day 0 through Week 52
Secondary	Volume of distribution		Day 0 through Week 52
Secondary	Terminal half life		Day 0 through Week 52
Secondary	Area under plasma concentration versus time curve		Week 2 to Week 24
Secondary	Incidence of treatment-related adverse events (safety)		Until End-of-Study follow-up at Week 52
Secondary	Immunogenicity	Human anti-chimeric antibody analysis	Baseline, Weeks 12, 16, 24, and 52
Secondary	Area under the depletion-time curve of CD19+ B-cell		Day 0 to Day 15, Day 0 to Week 12, Day 0 to Week 24, and Day 0 to Week 52 (end of study)
Secondary	Change from Baseline in CD4+ T-cell counts		Day 0 through Week 52
Secondary	American College of Rheumatology (ACR) criteria 20, 50, 70 response rate		Weeks 4, 8, 12, 16, 24 and 52 and over time from Baseline to Week 52
Secondary	Swollen and tender joint count		From Baseline to Week 52
Secondary	Subject's assessment of arthritis pain	2010 ACR/European League Against Rheumatism (EULAR) Classification Criteria for RA	From Baseline to Week 52