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

NCT03147248 | Completed Phase 3 Results DMC

• 2 other identifiers: CT-P13 3.5 (SC)2016-002125-11
• Study Type: interventional
• Target: 407
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (2)

• 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.

  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)

• 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.

  Week 22

Secondary Outcomes (4)

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

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

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

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

• Observed Trough Serum Concentration (Ctrough) of Infliximab (Part 2)

  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

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

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

Study Arms (6)

Cohort 1: CT-P13 IV 3 mg/kg

ACTIVE COMPARATOR

CT-P13 Intravenous (IV) (Infliximab), 3 mg/kg by IV infusion every 8 weeks (Part 1)

Biological: CT-P13

Cohort 2: CT-P13 SC 90 mg

EXPERIMENTAL

CT-P13 Subcutaneous (SC) (Infliximab), 90 mg by SC injection every other week (Part 1)

Biological: CT-P13

Cohort 3: CT-P13 SC 120 mg

EXPERIMENTAL

CT-P13 SC (Infliximab), 120 mg by SC injection every other week (Part 1)

Biological: CT-P13

Cohort 4: CT-P13 SC 180 mg

EXPERIMENTAL

CT-P13 SC (Infliximab), 180 mg by SC injection every other week (Part 1)

Biological: CT-P13

Arm 1: CT-P13 SC 120 mg

EXPERIMENTAL

CT-P13 SC (Infliximab), 120 mg by SC injection every other week with placebo intravenous infusion at Weeks 6, 14 and 22 (Part 2)

Biological: CT-P13

Arm 2: CT-P13 IV 3 mg/kg

ACTIVE COMPARATOR

CT-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)

Biological: CT-P13

Interventions

CT-P13 BIOLOGICAL

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

Also known as: Infliximab

Cohort 1: CT-P13 IV 3 mg/kg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Celltrion: lead

Study Sites (1)

Hanyang University Medical Center

Seoul, South Korea

Location

Related Publications (2)

• 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.

  PMID: 36534825 DERIVED

• 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.

  PMID: 33230526 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

CT-P13; Infliximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Study was divided into 2 parts; Part 1 was designed to find the optimal dose of CT-P13 SC with small number of patients (\~13 patients in each cohort) and Part 2 was designed to demonstrate noninferiority of CT-P13 SC with large number of patients.

Results Point of Contact

• Title: SungHyun Kim
• Organization: Celltrion. Inc.

SungHyun.Kim@celltrion.com

+82 32 850 5778

Study Officials

• MoonSun Choi

  Celltrion

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part 1 was open label.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2017
• First Posted: May 10, 2017
• Study Start: September 12, 2016
• Primary Completion: May 21, 2018
• Study Completion: April 15, 2019
• Last Updated: April 8, 2020
• Results First Posted: April 8, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)