Evaluating efficacy and safety of subcutaneous CT-P13 (CT-P13 SC) as maintenance therapy in patients with Crohn's disease

• Register: EUCTR
• Last refreshed on: 18 September 2023
• Main ID: EUCTR2019-001087-30-LV
• Date of registration: 04/06/2019
• Prospective Registration: Yes
• Primary sponsor: Celltrion, Inc
• Public title: Evaluating efficacy and safety of subcutaneous CT-P13 (CT-P13 SC) as maintenance therapy in patients with Crohn's disease
• Scientific title: A Randomized, Placebo-Controlled, Double-Blind, Phase 3 Study to Evaluate the Efficacy and Safety of the Subcutaneous Injection of CT-P13 (CT-P13 SC) as Maintenance Therapy in Patients With Moderately to Severely Active Crohn’s Disease
• Date of first enrolment: 25/07/2019
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-001087-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belarus, Brazil, Bulgaria, Chile, Croatia, Czech Republic, Estonia, France, Georgia, Germany, Greece, Hungary, India, Ireland, Israel, Italy, Latvia, Mexico, Moldova, Republic of, Peru, Poland, Portugal, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Turkey, Ukraine, United States

Contacts

• Name: Sung Hyun Kim
• Affiliation: Celltrion, Inc

• Name: Sung Hyun Kim
• Affiliation: Celltrion, Inc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patient is male or female aged 18 to 75 years, inclusive.
2. Patient who has moderately to severely active CD with a score on the CDAI of 220 to 450 points at Screening.
3. Patient with average (of 7 days) daily stool frequency =4 points (of Type 6 or Type 7 on the BSFS and/or an average (of 7 days) worst daily abdominal pain of =2 points (using 4 point scale) at Screening.
4. Patient who has a SES CD of =6 points for ileal-colonic CD or =4 points including ulcer score from at least 1 segment for ileal CD or colonic CD at Screening.
5. Patient who has CD, confirmed at any time in the past by radiography, histology, or endoscopy, of at least 3 months’ disease duration prior to the first administration of the study drug (Day 0).
6. Patient who has been treated for active CD but has not responded despite a full and adequate course of therapy with corticosteroids and/or immunosuppressants; or who is intolerant to or has medical contraindications for such therapies.
7. Patient who is receiving a stable dose of the following CD treatments or currently not receiving CD treatment during the specified time frame:
• Azathioprine (AZA), 6-mercaptopurine (6-MP) or Methotrexate (MTX) for at least 8 weeks prior to the first administration of the study drug (Day 0)
• Oral corticosteroids at the equivalent dose of 20 mg/day or less of prednisone for at least 2 weeks prior to the first administration of the study drug (Day 0)
• Oral budesonide at a dose of 6 mg/day or less for at least 4 weeks prior to the first administration of the study drug (Day 0)
• 5-Aminosalicylates (5-ASA) or antibiotics (i.e., ciprofloxacin, metronidazole) for at least 4 weeks prior to the first administration of the study drug (Day 0)
8. Patient who has adequate renal and hepatic function at Screening as defined by the following clinical chemistry results:
• Serum creatinine <1.5×upper limit of normal (ULN) or an estimated creatinine clearance level >50 mL/min (by Cockcroft-Gault formula)
• Serum alanine aminotransferase <2.5×ULN
• Serum aspartate aminotransferase <2.5×ULN
• Serum total bilirubin <2×ULN
9. Patient who has the following clinical hematology results at Screening:
• Hemoglobin =8.5 g/dL (SI [Système International d'Unités] units: =85 g/L or 5.28 mmol/L)
• White blood cell count =3.5×103 cells/µL (SI units: =3.5×109 cells/L)
• Neutrophil count =1.5×103 cells/µL (SI units: =1.5×109 cells/L)
• Platelet count =100×103 cells/µL (SI units: =100×109 cells/L)
10. Patient (or legal guardian, if applicable) who is informed of the full nature and purpose of the study, including possible risks and side effects, has the ability to cooperate with the investigator and is given ample time and opportunity to read or understand verbal and/or written instructions, and has signed and dated the written informed consent form (ICF) prior to participation in the study.
11. For both male and female patients, the patient and his or her partner of childbearing potential who agree to use one of the following medically acceptable methods of contraception during the course of the study and for 6 months following discontinuation of study drug (excluding women who are not of childbearing potential and men who have been sterilized):
• Barrier contraceptives (male condom, female condom, or diaphragm with a spermicidal gel)
• Hormonal contraceptives (implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings)
• Intrauterine
Exclusion criteria:
1. Patient who has previously received either a TNFa inhibitor or biological agent within 5 half-lives prior to the first administration of the study drug (Day 0).
2. Patient who has previously demonstrated inadequate response or intolerance to TNFa inhibitors for the treatment of CD.
3. Patient who has previously received infliximab for treatment of CD or other disease.
4. Patient who has allergies to any of the excipients of infliximab or any other murine and/or human proteins, or has a hypersensitivity to immunoglobulin products.
5. Patient who has received or has a plan to receive any of following prohibited medications or treatments:
• Parenteral corticosteroids for the treatment of CD within 2 weeks prior to the first administration of the study drug (Day 0)
• Janus kinase (JAK) inhibitors therapy including but not limited to tofacitinib and baricitinib within 4 weeks prior to the first administration of the study drug (Day 0)
• Alkylating agents within 12 months prior to the first administration of the study drug (Day 0)
• Cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 8 weeks prior to the first administration of the study drug (Day 0)
• Live or live-attenuated vaccine within 4 weeks prior to the first administration of the study drug (Day 0)
• Abdominal surgery for, including but not limited to, active gastrointestinal bleeding, peritonitis, intestinal obstruction, gastrointestinal resection or intra abdominal or pancreatic abscess requiring surgical drainage within 6 months prior to the first administration of the study drug (Day 0)
• Nonautologous stem cell therapy (e.g., Prochymal) within 12 months prior to the first administration of the study drug (Day 0)
• Apheresis (e.g., Adacolumn apheresis) for the treatment of CD within 3 weeks prior to the first administration of the study drug (Day 0)
• Use of total parenteral nutrition within a month prior to the first administration of the study drug (Day 0)
• Use of exclusive enteral nutrition for more than 3 consecutive days within a month or any single day of exclusive enteral nutrition within 2 weeks prior to the first administration of the study drug (Day 0)
6. Patient who has a current or history of any of the following infections:
• Known infection with hepatitis B or hepatitis C (active or carrier state), or infection with human immunodeficiency virus (HIV). However, a patient who is without cirrhosis of liver and recovered from a past hepatitis B or hepatitis C infection can be enrolled. In case of hepatitis C infection, patient who has achieved a sustained virologic response (SVR) for at least 12 weeks after completing the treatment for hepatitis C infection can be enrolled.
• 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 (Day 0)
• Other serious infection, in the investigator’s opinion, within 6 months prior to the first administration of the study drug (Day 0)
• Other chronic or recurrent infection, in the investigator’s opinion, within 6 weeks prior to the first administration of the study drug (Day 0)
• Past or current granulomatous infections or opportunistic infections (e.g., herpes zoster, cytomegalovirus, Pneumocystis carinii, aspergillosis, or mycobacteria other than TB) or invasive fungal infection (e.g., histoplasmosis)
7. Patient who has a medical condition including 1 or more of the following:
• Di

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderately to Severely Active Crohn’s Disease
MedDRA version: 20.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Code: CT-P13
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Current Sponsor code: CT-P13
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 120-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Trade Name: Inflectra
Product Code: CT-P13
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Primary end point(s): • Clinical remission at Week 54, defined as an absolute CDAI score of <150 points
• Endoscopic response at Week 54, defined as a 50% decrease in SES-CD score from the baseline value

Secondary Objective: To evaluate additional efficacy, PK, pharmacodynamics (PD) and overall safety including immunogenicity

Main Objective: To demonstrate superiority of CT-P13 SC over Placebo SC based on clinical remission and endoscopic response at Week 54.

Timepoint(s) of evaluation of this end point: The primary endopoint evaluation will be conducted at Week 54.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Key secondary endopoints evaluations will be conducted at Week 54 and other secondary endopoints evaluations will be conducted at time points described in protocol. PK, PD and safety assessments will be perfored at the time points specificed in the schedule of events (Table 10-1 and 10-2).

Secondary end point(s): Key Secondary endpoints
• CDAI-100 response at Week 54, defined as a decrease in CDAI score of 100 points or more from the baseline value
• Clinical remission at Week 54, defined as an average worst daily abdominal pain score of = 1 (using 4-point scale), and an average loose/watery stool frequency score of = 3 (of Type 6 or Type 7 on BSFS) with no worsening in either score compared to the baseline value
• Corticosteroid-free remission at Week 54, defined as being in clinical remission (by an absolute CDAI score of <150) in addition to not receiving oral corticosteroid for at least 8 weeks prior to Week 54, among the patients who used oral corticosteroids at baseline
• Endoscopic remission at Week 54, defined as an absolute SES-CD score of = 4 and at least 2-point reduction from the baseline value with no sub-score of >1
Other Secondary endpoints:
• Clinical remission, defined as an absolute CDAI score of <150 points
• Maintenance of clinical remission at Week 54, defined as being in clinical remission by CDAI score of <150 points, among the patients in clinical remission at Week 10
• Sustained clinical remission at both Week 22 and Week 54, defined as an average worst daily abdominal pain score of =1 (using 4-point scale), and an average loose/watery stool frequency score of =3 (of Type 6 or Type 7 on BSFS) at both Week 22 and Week 54 with no worsening in either score compared to the baseline value
• CDAI-70 response, defined as a decrease in CDAI score of 70 points or more from the baseline value
• CDAI-100 response, defined as a decrease in CDAI score of 100 points or more from the baseline value
• Maintenance of clinical response at Week 54, defined as being in CDAI-100 response at Week 54, among the patients in CDAI-100 response at Week 10
• Sustained clinical response at both Week 22 and Week 54, defined as a reduction from the baseline value in average worst daily abdominal pain score (using 4-point scale), and/or in average daily loose/watery stool frequency (of Type 6 or Type 7 on BSFS) at both Week 22 and Week 54
• Endoscopic remission, defined as an absolute SES-CD score of =4 and at least 2-point reduction from the baseline value with no sub-score of >1
• Endoscopic response, defined as a 50% decrease in SES-CD score from the baseline value
• Patient global scale, defined as a question that asks a patient’s position on achieving remission from his or her CD symptoms (Yes or No)
• Short Inflammatory Bowel Disease Questionnaire (SIBDQ)
Pharmacokinetic Assessments:
For all patients, Ctrough will be assessed up to Week 52 and Cmax will be assessed at Week 6. Blood samples for PK analysis will be collected at pre-dose of Weeks 0, 2, 6, 10, 14, 22, 30, 38, 46, 54, and within 15 minutes after the end of the study drug infusion of Week 6.
For patients who agreed to collect further blood samples, additional blood samples for further Population PK analysis will be collected at following time points:
• Any time between 48 hours and 72 hours after study drug administration of Week 22
• Any time between 120 hours and 168 hours after study drug administration of Week 22
• Pre-dose of Week 24
Pharmacodynamic Assessments:
• Fecal calprotectin
• C-reactive protein (CRP)
Safety Assessments:
Safety assessments will be performed on immunogenicity, hypersensitivity monitoring, vital sign measurements, weight, 12-lead ECGs, monitoring of TB signs and symptoms, monitoring of cardiovascular disease related signs and symptoms, chest X ray, IGRA, hepatitis B and C and HIV-1 and -2 status, NYHA functional classification assessment, diabetes mellitus, stool microbiology, physical examination findings, AEs, AEs of special interest (infusion-related reaction/systemic injection reaction, infection, delayed hypersensitivity, localized injection site reaction, malignancy), monitoring of drug-induced liver injury, pregnancy testing, clinical laboratory analyses, local site pain using 100 mm Visual Analogue Scale, and prior and concomitant medications.
In case of delayed hypersensitivity including serum sickness-like reactions, the following assessments will be additionally performed to determine serum sickness during the study period:
• Immunogenicity
• Clinical laboratory analyses
• Complement (C3, C4) and total hemolytic complement

Secondary ID(s)

CT-P13_3.8

Source(s) of Monetary Support

Celltrion, Inc

Ethics review

Status: Approved
Approval date: 28/06/2019
Contact: