A clinical study to assess the safety, tolerability and clinical effects of MT 1303 in subjects with moderate to severe active Crohn’s Disease

• Register: EUCTR
• Last refreshed on: 14 November 2016
• Main ID: EUCTR2014-002556-77-HU
• Date of registration: 09/10/2014
• Prospective Registration: Yes
• Primary sponsor: Mitsubishi Tanabe Pharma Corporation (MTPC)
• Public title: A clinical study to assess the safety, tolerability and clinical effects of MT 1303 in subjects with moderate to severe active Crohn’s Disease
• Scientific title: A Phase II, Multicentre, Randomised, Double-Blind, Parallel Group, Placebo Controlled Study to Evaluate Safety, Tolerability and Clinical Efficacy of MT 1303 in Subjects with Moderate to Severe Active Crohn’s Disease
• Date of first enrolment: 18/11/2014
• Target sample size: 80
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002556-77
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes 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): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, France, Germany, Hungary, Israel, Italy, Japan, Netherlands, Poland, Slovakia

Contacts

• Name: General Information
• Affiliation: Mitsubishi Tanabe Pharma Europe Ltd (MTPE)

• Name: General Information
• Affiliation: Mitsubishi Tanabe Pharma Europe Ltd (MTPE)

Key inclusion & exclusion criteria

Inclusion criteria:
1. Able to provide written informed consent and to comply with the requirements of the Protocol
2. Male or female subjects aged between 18 and 65 years (inclusive). For subjects of reproductive potential, two methods of contraception must be used throughout the study and for 12 weeks after cessation of study medication. At least one of the methods of contraception must be a barrier method.
3. Diagnosis of CD (involving small intestine and/or colon), confirmed at the time by endoscopy and histology at least 3 months prior to Visit 1 (Screening)
4. Previous use of corticosteroids or immunosuppressants (such as azathioprine [AZA]/ 6-mercaptopurine [6-MP] or methotrexate [MTX]) or anti-TNF-alpha agents (such as infliximab, adalimumab or certolizumab pegol) for the treatment of CD
5. Moderate to severe active CD defined by a CDAI score of =220 to =450 points at Visit 1
6. C-reactive protein (CRP) =5 mg per litre (/L) and/or faecal calprotectin =250 µg/g
7. A negative stool test result for Clostridium difficile (C. difficile) toxin at Visit 1
8. Negative results for both QuantiFERON-TB Gold (or T-SPOT) test and chest x-ray (i.e., no evidence of tuberculosis [TB]) at Visit 1

For detailed information, please refer to the Protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 79
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion criteria:
1. Diagnosis of ulcerative colitis, indeterminate colitis, pseudomembranous colitis or coeliac disease
2. Enterocutaneous, abdominal or pelvic active fistulae, abscesses or fistulae likely to require surgery during the study
3. Gastrointestinal (GI) surgery (including appendectomy) within 12 weeks prior to Visit 2 (Baseline) or has surgery planned or deemed likely to require surgery for CD during the study
4. History or evidence of ileostomy, colostomy, rectal pouch, significant stenosis or extensive resection in GI tract that could impair the drug absorption or interfere with the objectives of the study, as judged by the Investigator
5. History or evidence of unresected adenomatous colonic polyps or colonic mucosal dysplasia
6. Chronic use of opioid for chronic pain which, in the opinion of the Investigator, would influence the subject reported CDAI parameters.
7. Use of concomitant medications as described in the protocol.
8. Presence or history of clinically significant disease (except CD) that could interfere with the objectives of the study or the safety of the subject, as judged by the Investigator
9. Body weight =35 kg at Visit 1
10. Presence or history of any of cardiovascular diseases as decsribed in the protocol.
11. Need for, or likely need for treatment with Class I or Class III anti-arrhythmic drugs, or with beta-blockers or heart-rate-lowering calcium-channel blockers, or with any other drugs which can reduce the heart rate
12. Known high risk for QT/QTc prolongation such as a family history of long QT syndrome or sudden death
13. History or known presence of cerebrovascular diseases
14. Presence or history (within 5 years prior to initial screening) of malignancy, except for successfully treated basal cell and in situ squamous cell carcinomas of the skin
15. Known history of recurrent or chronic infection such as TB, hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
16. Receipt of live vaccine within 4 weeks prior to Visit 2
17. Diagnosis of diabetes mellitus (Type I or II)
18. Presence or prior history of macular oedema, uveitis or evolutive retinopathy, or any other condition that could increase the risk of macular oedema in the opinion of the Investigator
19. History of substance abuse (drug or alcohol) or any other factor that limits the subject’s ability to cooperate with the study procedures.
20. Known history of allergy, hypersensitivity or any serious reaction to any component of the study medication
21. Previous treatment with any investigational agent within 12 weeks prior to Visit 1 OR five half-lives of the investigational product, whichever is the longer.
22. WBC count <3,500/µL at Visit 1
23. Lymphocyte count <800/µL at Visit 1
24. LFT (aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) =2 x ULN at Visit 1
25. HbA1c >6.5% at Visit 1
26. Negative or indeterminate results for antibodies (IgG) to Varicella Zoster virus (VZV) at Visit 1
27. [For female subjects only] A positive pregnancy test at Visit 1 (serum beta-human chorionic gonadotropin [hCG] level or urine dipstick) or Visit 2 (urine dipstick)
28. Low heart rate (<50 beats per minute [bpm]) in 12-lead ECG at Visit 1 or Visit 2 (pre-dose)
29. QTcF interval =450 milliseconds (msec) in 12-lead ECG at Visit 1 or Visit 2 (pre-dose)
30. Clinically significant abnormal findings in 12-lead ECG (at Visit 1 or Visit 2 [pre-dose]) and/or in Holter ECG (at Visit 1) that the Investigator considers m

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

Health Condition(s) or Problem(s) studied

Subjects with moderate to severe crohn's disease
MedDRA version: 17.0 Level: LLT Classification code 10013099 Term: Disease Crohns System Organ Class: 100000004856

Therapeutic area: Body processes [G] - Immune system processes [G12]

Intervention(s)

Product Name: MT-1303
Product Code: MT-1303
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: MT-1303
Current Sponsor code: MT-1303
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.4-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: • To evaluate the safety and tolerability of MT-1303 in subjects with moderate to severe active CD
• To evaluate the clinical efficacy of MT-1303 in subjects with moderate to severe active CD.

Secondary Objective: • To explore the pharmacokinetics (PK) of MT-1303 in subjects with moderate to severe active CD
• To explore the pharmacodynamic (PD) effect of MT 1303 in subjects with moderate to severe active CD.

Timepoint(s) of evaluation of this end point: Various time points throughout the study - please refer to the detailed ‘Time and Events Schedule’ table in the protocol for full details.

Primary end point(s): The proportion of subjects who achieve a 100-point decrease from Baseline in CDAI score (i.e., CDAI 100) at Visit 6 (Week 12)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Various time points throughout the study - please refer to the detailed ‘Time and Events Schedule’ table in the protocol for full details.

Secondary end point(s): Efficacy
• Proportion of subjects who achieve a 70-point decrease from Baseline in CDAI score (i.e., CDAI 70) at Protocol-scheduled visits.
• Proportion of subjects who achieve a 100-point decrease from Baseline in CDAI score (i.e., CDAI 100) at other Protocol-scheduled visits.
• Proportion of subjects who achieve clinical remission (i.e., CDAI score of <150) at Protocol-scheduled visits.
• CDAI score and change from Baseline in CDAI score at Protocol-scheduled visits.

Pharmacodynamics
• Lymphocyte count and lymphocyte subsets, their change from Baseline, and percentage of Baseline at Protocol-scheduled visits.

Pharmacokinetics
• PK concentration of MT-1303 and its active metabolite MT-1303-P at Protocol-scheduled visits.

Exploratory Endpoints:
• Time to the first clinical remission during the study
• Time to the first clinical response of CDAI 100 during the study
• Time to the first clinical response of CDAI 70 during the study
• Change from Baseline in CDAI sub-scores
• CRP and faecal calprotectin value and their change from Baseline at Protocol-scheduled visits.

Safety
• Incidence and severity of adverse events (AEs)
• Physical examination
• 12-lead ECG parameters
• 24-h/48-h Holter ECG parameters
• Vital signs (pulse rate, systolic and diastolic blood pressure [BP], and body temperature)
• Safety laboratory parameters
• Optical coherence tomography (OCT).

Secondary ID(s)

2014-002556-77-CZ

MT-1303-E13

Source(s) of Monetary Support

Mitsubishi Tanabe Pharma Corporation (MTPC)