Rheumatoid ArthritisPhase 1NCT03161457
A Study of JHL1101 Versus MabThera® in Subjects With Severe Rheumatoid Arthritis
A Phase 1 study testing JHL1101 and MabThera in people with Rheumatoid Arthritis and Arthritis, Rheumatoid, run by JHL Biotech, Inc. at 32 sites in 11 countries.
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)… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Rheumatoid Arthritis, Arthritis, Rheumatoid
- What is being tested?
- JHL1101 and MabThera
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 153 participants
- Where
- 32 sitesin 11 countries
- Study dates
- 27 Feb 2017to 16 Apr 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 22Show fewer
- 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.
Trial locations and contacts
32 sites in 11 countries.
32 sites in 11 countries
Russia8 sites
JHL Biotech Investigational Site
Kazan', 420103
JHL Biotech Investigational Site
Moscow, 111539
JHL Biotech Investigational Site
Moscow, 119049
JHL Biotech Investigational Site
Saint Petersburg, 197341
JHL Biotech Investigational Site
Saint Petersburg, 197342
JHL Biotech Investigational Site
Samara, 443095
JHL Biotech Investigational Site
Saratov, 410026
JHL Biotech Investigational Site
Yaroslavl, 150062
Ukraine5 sites
JHL Biotech Investigational Site
Kharkiv, 61039
JHL Biotech Investigational Site
Kyiv, 03680
JHL Biotech Investigational Site
Lviv, 79010
JHL Biotech Investigational Site
Poltava, 36011
JHL Biotech Investigational Site
Vinnytsia, 21018
Germany4 sites
JHL Biotech Investigational Site
Bad Doberan, 18209
JHL Biotech Investigational Site
Hildesheim, 31134
JHL Biotech Investigational Site
Magdeburg, 39120
JHL Biotech Investigational Site
Rendsburg, 24768
Bulgaria3 sites
JHL Biotech Investigational Site
Plovdiv, 4002
JHL Biotech Investigational Site
Sofia, 1336
JHL Biotech Investigational Site
Sofia, 1612
Taiwan3 sites
JHL Biotech Investigational Site
Taichung, 402
JHL Biotech Investigational Site
Taipei, 100
JHL Biotech Investigational Site
Taipei, 11490
Bosnia and Herzegovina2 sites
JHL Biotech Investigational Site
Banja Luka, 78000
JHL Biotech Investigational Site
Bijeljina, 76300
Poland2 sites
JHL Biotech Investigational Site
Poznan, 61-113
JHL Biotech Investigational Site
Wroclaw, 50-420
United Kingdom2 sites
JHL Biotech Investigational Site
London, E11 1NR
JHL Biotech Investigational Site
Southampton, SO16 6YD
About this study
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
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.
Read the 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.
- Conditions
- Rheumatoid Arthritis, Arthritis, Rheumatoid
- Being tested
- JHL1101, MabThera
- Keywords
- RA, Moderate RA, Moderate Rheumatoid Arthritis, Severe RA, Severe Rheumatoid Arthritis, Moderate to Severe RA, Moderate to Severe Rheumatoid Arthritis
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JHL1101Biological
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
MabTheraBiological
Also called Rituximab
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
| Study group | Role | What they receive |
|---|---|---|
| JHL1101 | Experimental | Each subject will receive 2 intravenous infusions of 1000 mg JHL1101: the first infusion on Baseline and the second on Day 15. Receives: Biological: JHL1101 |
| MabThera | Active comparator | Each subject will receive 2 intravenous infusions of 1000 mg MabThera: the first infusion on Baseline and the second on Day 15 (Visit 5). Receives: Biological: MabThera |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under plasma concentration versus time curve (AUC)
Measured: Day 0 through Week 52
Trough Concentration
Measured: Day 15
Maximum Concentration (Cmax)
Measured: Day 15
Secondary outcomes (14)
AUC
Measured: Up to Week 12
Time to maximum plasma concentration
Measured: Day 0 through Week 52
Cmax
Measured: Day 0 through Week 52
Total body clearance
Measured: Day 0 through Week 52
Volume of distribution
Measured: Day 0 through Week 52
Terminal half life
Measured: Day 0 through Week 52
Area under plasma concentration versus time curve
Measured: Week 2 to Week 24
Incidence of treatment-related adverse events (safety)
Measured: Until End-of-Study follow-up at Week 52
Immunogenicity
Human anti-chimeric antibody analysis
Measured: Baseline, Weeks 12, 16, 24, and 52
Area under the depletion-time curve of CD19+ B-cell
Measured: Day 0 to Day 15, Day 0 to Week 12, Day 0 to Week 24, and Day 0 to Week 52 (end of study)
Change from Baseline in CD4+ T-cell counts
Measured: Day 0 through Week 52
American College of Rheumatology (ACR) criteria 20, 50, 70 response rate
Measured: Weeks 4, 8, 12, 16, 24 and 52 and over time from Baseline to Week 52
Swollen and tender joint count
Measured: From Baseline to Week 52
Subject's assessment of arthritis pain
2010 ACR/European League Against Rheumatism (EULAR) Classification Criteria for RA
Measured: From Baseline to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2017
- Study start27 Feb 2017
- Primary completion16 Apr 2019
- Study completion16 Apr 2019
Why it stopped: The development was stopped due to company's strategy consideration
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 153 participants (actual)
Sponsor and investigators
- Lead sponsor
- JHL Biotech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03161457
- Sponsor's protocol ID
- JHL-CLIN-1101-01
- Status last verified
- Jan 2020
- First submitted
- 21 Apr 2017
- Last updated
- 9 Jan 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03161457
- Acronym / sponsor ID
- JHL-CLIN-1101-01
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The development was stopped due to company's strategy consideration
- Enrolment
- 153 participants (actual)
- Lead sponsor
- JHL Biotech, Inc.Industry (pharma, biotech, devices)
- Study start
- 27 Feb 2017 (actual)
- Primary completion
- 16 Apr 2019 (actual)
- Study completion
- 16 Apr 2019 (actual)
- First posted
- 19 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| JHL1101 | Experimental | Biological: JHL1101Each subject will receive 2 intravenous infusions of 1000 mg JHL1101: the first infusion on Baseline and the second on Day 15. |
| MabThera | Active comparator | Biological: MabTheraEach subject will receive 2 intravenous infusions of 1000 mg MabThera: the first infusion on Baseline and the second on Day 15 (Visit 5). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| JHL11011000 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 | Biological | JHL1101 |
| MabTheraAlso: Rituximab1000 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 | Biological | MabThera |
Primary outcome
Area under plasma concentration versus time curve (AUC)
Time frame: Day 0 through Week 52
Trough Concentration
Time frame: Day 15
Maximum Concentration (Cmax)
Time frame: Day 15
14 secondary outcomes
AUC
Time frame: Up to Week 12
Time to maximum plasma concentration
Time frame: Day 0 through Week 52
Cmax
Time frame: Day 0 through Week 52
Total body clearance
Time frame: Day 0 through Week 52
Volume of distribution
Time frame: Day 0 through Week 52
Terminal half life
Time frame: Day 0 through Week 52
Area under plasma concentration versus time curve
Time frame: Week 2 to Week 24
Incidence of treatment-related adverse events (safety)
Time frame: Until End-of-Study follow-up at Week 52
Immunogenicity
Time frame: Baseline, Weeks 12, 16, 24, and 52
Area under the depletion-time curve of CD19+ B-cell
Time frame: Day 0 to Day 15, Day 0 to Week 12, Day 0 to Week 24, and Day 0 to Week 52 (end of study)
Change from Baseline in CD4+ T-cell counts
Time frame: Day 0 through Week 52
American College of Rheumatology (ACR) criteria 20, 50, 70 response rate
Time frame: Weeks 4, 8, 12, 16, 24 and 52 and over time from Baseline to Week 52
Swollen and tender joint count
Time frame: From Baseline to Week 52
Subject's assessment of arthritis pain
Time frame: From Baseline to Week 52
Results and safety
The study was stopped early (reason given: The development was stopped due to company's strategy consideration). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
32 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing JHL1101 and MabThera in people with Rheumatoid Arthritis and Arthritis, Rheumatoid, run by JHL Biotech, Inc. at 32 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in Russia, Ukraine, Germany, Bulgaria, Taiwan and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The development was stopped due to company's strategy consideration). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under plasma concentration versus time curve (AUC) (time frame: Day 0 through Week 52). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2020.