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Rheumatoid ArthritisPhase 3NCT03147248

A Phase I/III Study to Evaluate Efficacy, PK and Safety Between CT-P13 SC and CT-P13 IV in Patients With Active RA

A Phase 3 study testing CT-P13 in people with Rheumatoid Arthritis, run by Celltrion at 1 site in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a Phase I/III Study to Evaluate Efficacy, Pharmacokinetics and Safety between CT-P13 SC and CT-P13 IV in Patients with Active Rheumatoid Arthritis (RA). Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
CT-P13
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
407 participants
Where
1 siteSouth Korea
Study dates
12 Sep 2016to 15 Apr 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient is male or female between 18 and 75 years old, inclusive.
  • Patient has a diagnosis of RA according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for at least 6 months
  • Patient has active disease as defined by the presence of 6 or more swollen joints (of 28 assessed), 6 or more tender joints (of 28 assessed) and serum C-reactive protein (CRP) concentration >0.6 mg/dL
  • Patient who completed at least 3 months of treatment of oral or parenteral dosing with Methotrexate between 12.5 to 25 mg/kg (between 10 to 25 mg/week in Korea) and on stable dosing with Methotrexate for at least 4 weeks prior to the first administration of the study drug.

Who cannot join

  • Patient who has previously received a biological agent for the treatment of RA and/or a TNFα inhibitor for the treatment of other disease
  • Patient who has allergies to any of the excipients of infliximab or any other murine and/or human proteins or patient with a hypersensitivity to immunoglobulin product
  • Patient who had current or past history of chronic infection with hepatitis C or human immunodeficiency virus (HIV)-1 or -2 or current infection with hepatitis B
  • Patient who had acute infection requiring oral antibiotics within 2 weeks or parenteral injection of antibiotics within 4 weeks prior to the first administration of the study drug, other serious infection within 6 months prior to the first administration of study drug or recurrent herpes zoster or other chronic or recurrent infection within 6 weeks prior to the first administration of the study drug.
  • Patient who had an indeterminate result for interferon-γ release assay (IGRA) or latent tuberculosis (TB) at Screening. For Part 2, if IGRA result was indeterminate at Screening, 1 retest was possible during the screening. If the repeated IGRA result was negative, the patient could be included in the study.

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Hanyang University Medical Center

    Seoul

Other trials in South Korea

About this study

Official title: A Randomized, Parallel-Group, Phase I/III Study to Evaluate Efficacy, Pharmacokinetics and Safety Between Subcutaneous CT-P13 and Intravenous CT-P13 in Patients With Active Rheumatoid Arthritis

This is a Phase I/III Study to Evaluate Efficacy, Pharmacokinetics and Safety between CT-P13 SC and CT-P13 IV in Patients with Active Rheumatoid Arthritis (RA).

Read the detailed description

A new subcutaneous infliximab formulation is developed by Celltrion, Inc. as an alternative to the intravenous regimen where subcutaneous infliximab injection typically takes less than 2 minutes. The availability of a subcutaneous formulation of infliximab would increase the treatment options available to patients, particularly those wishing to self-administer their therapy. This Phase I/III Study randomized, double-blinded (Part 2 only), multicenter, parallel-group study was designed to evaluate Efficacy, Pharmacokinetics and Safety between Subcutaneous CT-P13 and Intravenous CT-P13 in Patients with Active RA.

Being tested
CT-P13
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CT-P13Biological

    Also called Infliximab

    CT-P13 (3 mg/kg) by IV infusion administered as a 2 hour IV infusion per dose every 8 weeks

  • CT-P13Biological

    Also called Infliximab

    CT-P13 (90 mg) by single SC injection every other week

  • CT-P13Biological

    Also called Infliximab

    CT-P13 (120 mg) by single SC injection every other week

  • CT-P13Biological

    Also called Infliximab

    CT-P13 (180 mg) by double SC 90 mg injections every other week

  • CT-P13Biological

    Also called Infliximab

    CT-P13 (120 mg) by single SC injection every other week with placebo IV at Weeks 6, 14 and 22.

  • CT-P13Biological

    Also called Infliximab

    CT-P13 (3 mg/kg) by IV infusion administered as a 2 hour IV infusion per dose every 8 weeks with placebo SC at Week 6 and every other week thereafter up to Week 28

Study groups in NCT03147248
Study groupRoleWhat they receive
Cohort 1: CT-P13 IV 3 mg/kgActive comparatorCT-P13 Intravenous (IV) (Infliximab), 3 mg/kg by IV infusion every 8 weeks (Part 1)
Receives: Biological: CT-P13
Cohort 2: CT-P13 SC 90 mgExperimentalCT-P13 Subcutaneous (SC) (Infliximab), 90 mg by SC injection every other week (Part 1)
Receives: Biological: CT-P13
Cohort 3: CT-P13 SC 120 mgExperimentalCT-P13 SC (Infliximab), 120 mg by SC injection every other week (Part 1)
Receives: Biological: CT-P13
Cohort 4: CT-P13 SC 180 mgExperimentalCT-P13 SC (Infliximab), 180 mg by SC injection every other week (Part 1)
Receives: Biological: CT-P13
Arm 1: CT-P13 SC 120 mgExperimentalCT-P13 SC (Infliximab), 120 mg by SC injection every other week with placebo intravenous infusion at Weeks 6, 14 and 22 (Part 2)
Receives: Biological: CT-P13
Arm 2: CT-P13 IV 3 mg/kgActive comparatorCT-P13 IV (Infliximab), 3 mg/kg by IV infusion every 8 weeks with placebo subcutaneous injection at Week 6 and every 2 weeks thereafter up to Week 28 (Part 2)
Receives: Biological: CT-P13

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Area Under the Concentration-time Curve (AUCτ) of Infliximab at Steady State (Part 1)

    For Part 1, the primary pharmacokinetic (PK) endpoint of the AUCτ (area under the concentration-time curve) at steady state between Week 22 and Week 30 was analyzed in patients who received all doses (full) of study drug up to Week 30 (prior to Week 30) in the PK population. All patients in SC cohorts were randomly assigned at Week 14 in a 1:1 ratio to either Group A or B for PK monitoring visit period (Week 22 and Week 30). Therefore, AUCτ was calculated at Week 22 for Cohort 1: CT-P13 IV 3 mg/kg, Weeks 22 and 26 for Group A of SC cohorts, and Weeks 24 and 28 for Group B of SC cohorts.

    Measured: Weeks 22 (pre-dose to 216 hours post-dose), 24 (14 days after start of administration [SOA] at Week 22), 26 (pre-dose) and 28 (42 days after SOA at Week 22), and Week 30 (pre-dose)

  2. Change From Baseline of Disease Activity Score Using 28 Joint Counts (DAS28) (CRP) at Week 22 (Part 2)

    For Part 2, the primary efficacy endpoint was to demonstrate that CT-P13 SC 120 mg is non-inferior to CT-P13 IV 3 mg/kg at Week 22, as determined by clinical response according to mean change from baseline in DAS28 (CRP) at Week 22, using Analysis of Covariance (ANCOVA). Change from baseline for ANCOVA was defined as decrease from baseline and calculated as (DAS28 [CRP] at baseline - DAS28 [CRP] at Week 22). DAS28 (CRP) was calculated using the following formula: DAS28 (CRP) equals(=) (0.56 multiplied by [*] the square root [√] of TJC28 [tender joint count]) plus (+) (0.28 * √ of SJC28 [swollen joint count]) + (0.36 * the natural logarithm [ln](CRP [mg/L] + 1)) + (0.014 * patient global disease activity [GH] on visual analogue assessment [VAS]) + 0.96. DAS28 (CRP) provides a number on a scale from 0 to 10 indicating the current activity of patients with RA. DAS28 (CRP) score above 5.1 indicates high disease activity, whereas DAS28 (CRP) score below 3.2 indicates low disease activity.

    Measured: Week 22

Secondary outcomes (4)

  1. Mean Actual Value of Disease Activity Score Using 28 Joint Counts (DAS28 [CRP]) (Part 2)

    The secondary endpoint was defined as descriptive statistics of actual value in disease activity measured by DAS28 (CRP) up to Week 54. The results up to Week 6 represented the efficacy of CT-P13 IV loading dose (3 mg/kg) regardless of randomized treatment arm (CT-P13 SC or CT-P13 IV) in both treatment arms. DAS28 (CRP) was calculated according to the following formula: DAS28 (CRP) = (0.56* √ of TJC28) + (0.28 * √ of SJC28) + (0.36 * ln(CRP [mg/L] + 1)) + (0.014 * GH on VAS) + 0.96. DAS28 (CRP) provides a number on a scale from 0 to 10 indicating the current activity of the patients with RA. DAS28 (CRP) score above 5.1 indicates high disease activity, whereas DAS28 (CRP) score below 3.2 indicates low disease activity.

    Measured: Baseline, Week 2, Week 6, Week 14, Week 22, Week 30, and Week 54

  2. Number of Patients Achieving Clinical Response According to American College of Rheumatology 20% Response (ACR20) (Part 2)

    The secondary endpoint was defined as number of patients achieving clinical response according to ACR20 (20% response, defined by ACR) between CT-P13 SC and CT-P13 IV groups. The results up to Week 6 represented the efficacy of CT-P13 IV loading dose (3 mg/kg) regardless of randomized treatment arm (CT-P13 SC or CT-P13 IV).

    Responder according to the ACR20 criteria defined as, if they are fulfilled, a decrease of at least 20% in number of tender joints and swollen joints (0-28), and 20% improvement in 3 of the followings: patient assessment of pain on VAS (0-100 mm), patient global assessment of disease activity on VAS (0-100 mm) and physician global assessment of disease activity on VAS (0-100 mm), health assessment questionnaire disability index and CRP or ESR (erythrocyte sedimentation rate).

    Measured: Week 2, Week 6, Week 14, Week 22, Week 30, and Week 54

  3. Observed Trough Serum Concentration (Ctrough) of Infliximab (Part 2)

    For evaluation of pharmacokinetics (PK), the secondary endpoint was defined as the analysis of trough concentration (concentration before the next study drug administration) of Infliximab up to Week 54. The samples were collected at Weeks 0, 2 and 6, and every 8 weeks up to Week 54. During PK monitoring visit (Weeks 22-30), samples were collected every 2 weeks according steady state PK sampling time point. All patients were randomly assigned at Week 14 in a 1:1:1:1 ratio to one of 4 groups (Groups A, B, C or D) for PK monitoring visit period. No PK results were obtained at Weeks 6 and 14 for SC group and Weeks 12, 20, 24, 26 and 28 for IV group due to 2 weeks and 8 weeks dosing interval, respectively.

    Measured: SC group: Weeks 0, 2, 12, 20, 22, 24, 26, 28, 36, 44, and 52; IV group: Weeks 0, 2, 6, 14, 22, 36, 44, and 52

  4. Mean Actual Value in Serum CRP Concentration (Pharmacodynamic Parameter) (Part 2)

    For evaluation of pharmacodynamic (PD), the secondary endpoint was defined as concentration of CRP between 2 treatment groups up to Week 54. The blood samples for CRP were collected at Weeks 0, 2 and 6, and every 8 weeks up to Week 54.

    Patient who received the other treatment than that to which they were assigned at any point was defined as mis-randomized. One patient in IV group was mis-randomized and analyzed as SC group for PD analysis.

    Measured: Baseline, Week 2, Week 6, Week 14, Week 22, Week 30, Week 38, Week 46, and Week 54

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 May 2017
  2. Study start12 Sep 2016
  3. Primary completion21 May 2018
  4. Study completion15 Apr 2019

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
407 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03147248
Sponsor's protocol ID
CT-P13 3.5 (SC)
Other IDs
2016-002125-11, 2016
Status last verified
Mar 2020
First submitted
7 May 2017
Last updated
8 Apr 2020
Data monitoring committee
Yes
FDA-regulated drug
No
Individual data sharing
No

Publications

  • Constantin A, Caporali R, Edwards CJ, Fonseca JE, Iannone F, Keystone E, Schulze-Koops H, Kwon T, Kim S, Yoon S, Kim DH, Park G, Yoo DH. Efficacy of subcutaneous vs intravenous infliximab in rheumatoid arthritis: a post-hoc analysis of a randomized phase III trial. Rheumatology (Oxford). 2023 Aug 1;62(8):2838-2844. doi: 10.1093/rheumatology/keac689.

    PubMed 36534825

  • Westhovens R, Wiland P, Zawadzki M, Ivanova D, Kasay AB, El-Khouri EC, Balazs E, Shevchuk S, Eliseeva L, Stanislavchuk M, Yatsyshyn R, Hrycaj P, Jaworski J, Zhdan V, Trefler J, Shesternya P, Lee SJ, Kim SH, Suh JH, Lee SG, Han NR, Yoo DH. Efficacy, pharmacokinetics and safety of subcutaneous versus intravenous CT-P13 in rheumatoid arthritis: a randomized phase I/III trial. Rheumatology (Oxford). 2021 May 14;60(5):2277-2287. doi: 10.1093/rheumatology/keaa580.

    PubMed 33230526

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing CT-P13 in people with Rheumatoid Arthritis, run by Celltrion at 1 site in South Korea.

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 4 inclusion and 5 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: finished, as of the sponsor's last update on 8 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 the Concentration-time Curve (AUCτ) of Infliximab at Steady State (Part 1) (time frame: Weeks 22 (pre-dose to 216 hours post-dose), 24 (14 days after start of administration [SOA] at Week 22), 26 (pre-dose) and 28 (42 days after SOA at Week 22), and Week 30 (pre-dose)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03147248, which also lists 2 linked publications.

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 8 Apr 2020.

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Clinical Trial NCT03147248 | AzTrials