| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
Crohn's disease, is an inflammatory disease of the intestines that may
affect any part of the digestive channel. It primarily causes abdominal
pain, diarrhea, vomiting, or weight loss. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10011401 |
| E.1.2 | Term | Crohn's disease |
| E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objective:
Part A
To evaluate the effect of TRK-170 on mucosal healing as measured by
Crohn's Disease Endoscopic Index of Severity (CDEIS) score based on
ileocolonoscopy and use this evaluation to decide which dose(s) of TRK-
170 should be used in Part B
Part B
To evaluate the efficacy of TRK-170 in patients with active CD as
measured by CDAI score |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
Part A
- to evaluate the efficacy of TRK-170 in patients with active CD as
measured by CDAI score
Part A and Part B
- to evaluate the safety and tolerability of TRK-170 in patients with
active CD
- to evaluate the PK characteristics of TRK-170 in patients with active CD
- to evaluate the effect of TRK-170 on faecal calprotectin excretion
- to evaluate the effect of TRK-170 on C-reactive protein (CRP) in plasma
- to evaluate the effect of TRK-170 on the Inflammatory Bowel Disease
Questionnaire (IBDQ) score
- to evaluate the PK-pharmacodynamic (PD) relationship of TRK-170 for
variables that may be affected by the treatment, i.e., CDEIS (Part A
only), CDAI and IBDQ scores, faecal calprotectin and plasma CRP levels |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Patient has to meet all of the following criteria to be eligible to enter the study:
1) Male and female patients aged 18 to 50 years
2) Patient has a diagnosis of CD at least 4 months prior but not more than 10 years before screening. The diagnosis should have been confirmed by endoscopic findings including histological examination
3) Patient has had disease activity with lesions in the colon within the past 12 months before dosing, as confirmed by ileocolonoscopy
4) Patient with moderately active CD at time of screening defined as a CDAI score of between 220 and 450
5) Patient has stable disease activity (stable for ≥ 2 weeks prior to screening) and not foreseen to require treatment with high dose steroids or other short term, potent treatments (e.g. TNF-α inhibitors) during the study period
6) Patient has an increased CRP level (> upper limit of normal) at
screening, as a sign of active disease, as judged by the investigator
7) Patient with a body weight of greater than 50 kg but less than 120 kg
8) Patient willing and able to participate in the study and provide signed informed consent
9) Patient agrees to use adequate contraceptive measures, in other words, Female patient who has not been post-menopausal for more than 3 months or female patients of childbearing potential must use adequate contraception (i.e. a method with less than 1% failure rate [e.g. diaphragm or condom used in combination with spermicidal cream, sterilization, an intrauterine device, or a vasectomised partner]) during and for at least 3 months after the last dose of IP. Females using hormonal contraception methods must also use an additional contraception method (as described above) during and for at least 3 months after the last dose of IP
or
Male patient who agrees to use condoms in combination with
spermicidal cream during the study and for three months after the last dose of the IP, or patient who has a female partner using adequate contraception as described above |
|
| E.4 | Principal exclusion criteria |
Patient meeting any of the following criteria will not be permitted to enter the study:
1) Increased risk of hypersensitivity or allergy to the IP or placebo product as judged by the investigator
2) Patient has had a clinically significant illness within 4 weeks prior to screening, at the investigator's discretion
3) Patient with clinically significant deviations in laboratory values as determined by the investigator
4) Patient who had a serious infection within 3 months, opportunistic infection within one month, or current signs or symptoms of severe, progressive or uncontrolled disease
5) Severe renal impairment defined as a predicted creatinine clearance of 30 mL/min or less, based on the Cockroft-Gault equation
6) Patient has a history of cancer or lymphoproliferative disease within the last 5 years
7) History of substance or alcohol abuse within the past one year prior to screening
8) Positive viral test result for hepatitis B or C or human HIV 1 or 2 or positive pre-study testing for major drugs of abuse or excessive alcohol consumption
9) Chest X-ray positive or suspected positive for active tuberculosis
10) Female patient currently pregnant or breast-feeding or intending to become pregnant during the study or within three months after the last dose of the IP
11) Female patient of childbearing age (unless surgically sterile) without a negative urine pregnancy test at screening and at enrollment
12) Patient currently has gastrointestinal disease other than CD (e.g., ulcerative colitis, short bowel syndrome, malabsorption, intestinal obstruction). This includes patients with an ostomy, ileal pouch, a previous ileo-rectal anastomosis, a history of procto-colectomy but not subtotal colectomy, draining fistula or abscess or are receiving enteral nutrition via a feeding tube or parenteral nutrition
13) Treatment with immunosuppressants or anti-cancer drugs (e.g., azathioprine, 6-MP, 6-thioguanin, methotrexate, mycophenolate mofetil, sirolimus (rapamycin), tacrolimus, thalidomide, cyclophosphamide, or cyclosporine) within the last 3 months prior to screening
14) Treatment with intravenous or rectal steroids for CD, antibiotics (e.g., metronidazole or ciprofloxacin) or continued repeated use of nonsteroidal anti-inflammatory agents (NSAIDs) within 2 weeks prior to screening
15) Treatment with Tysabri® or inhibitors of TNF-α within 8 weeks prior to screening
16) Treatment with a 5-ASA formulation (oral mesalazine) at a fixed dose of 2.4 g/day or higher (not exceeding the approved dose) within 1 week prior to screening
17) Patient who changed the dose of oral corticosteroids within 2 weeks prior to screening or ongoing treatment with prednisolone exceeding 25 mg/day or corresponding doses of other corticosteroids
18) Patient who stopped using oral corticosteroids within 4 weeks prior to screening
19) Patient has previous treatment failure or had an inadequate response or intolerance to biologic drugs for CD(e.g., Tysabri® or inhibitors of TNF-α)
20) Patient who had a previous GI surgical procedure (except
appendectomy and ileocecal resection) within 8 weeks of screening or foreseen to need GI surgery during the study
21) Patient has contributed blood (e.g., blood donation or clinical study participation) or suffered from blood loss, of at least 450 mL (1 unit of blood) within 90 days before screening or has donated plasma within 7 days prior to screening
22) Patient has participated in a clinical study in which he/she received an investigational drug within 3 months prior to dosing
23) Patient with unwillingness or inability to follow the procedures outlined in the study protocol
24) Patient considered by the investigator to be unsuitable to participate in the study for any other reason |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Part A
Change in CDEIS score from baseline to end of treatment (week 8)
Part B
The proportion of patients in remission as defined by a CDAI score of <150 at end of treatment (week 8) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Primary endpoint will be evaluated at Day 56 (+/-3 days)Week 8 |
|
| E.5.2 | Secondary end point(s) |
Part A
- The proportion of patients in remission as defined by a CDAI score of <150 at end of treatment (week 8)
Part A and Part B
- Proportion of responders as defined by a reduction in CDAI score by at least 70 at week 8 compared to baseline
- Safety and tolerability of TRK-170 in patients with active CD as
assessed by adverse events (AEs), vital signs and laboratory parameters
- PK characteristics of TRK-170
- Changes in faecal calprotectin concentration from baseline to week 8
- Changes in plasma CRP levels from baseline to week 8
- Changes in IBDQ score from baseline to week 8 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| All secondary endpoints will be evaluated at Day 56 (+/-3 days)Week 8 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 53 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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