| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10011401 |
| E.1.2 | Term | Crohn's disease |
|
| 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 is to demonstrate efficacy of CP-690,550 in inducing a clinical
response in subjects with moderate-to-severe Crohn’s disease. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
1. To evaluate the safety and tolerability of oral CP-690,550 in subjects with active Crohn’s disease.
2. To further evaluate the efficacy of CP-690,550 in inducing clinical remission and to
characterize the time to response and remission in subjects with active Crohn’s disease.
3. To characterize the pharmacokinetics of CP-690,550 in subjects with active Crohn’s
disease.
4. To evaluate the effect of treatment of CP-690,550 on Quality Of Life in subjects with active Crohn’s disease.
5. To demonstrate the change from baseline in following biomarkers: CRP, fecal
calprotectin. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subjects must be at least 18 years of age.
2. Males and females with clinical evidence of Crohn’s disease for at least 3 months
duration and moderate-to-severe disease at baseline, as defined by a Crohn’s Disease Activity Index (CDAI) score of 220 to 450 inclusive.
3. Visualization of the GI tract (radiology, scintigraphy or endoscopy) within 24 months prior to screening to confirm diagnosis and extent of Crohn’s disease.
4. Subjects currently receiving the following treatment regimens for Crohn’s Disease are eligible providing they are on stable dose for designated period of time:
• 5-ASA or sulfasalazine stable dose for at least 3 weeks prior to baseline and during
the study treatment period.
• Corticosteroids (prednisolone 30 mg or less or equivalent, budesonide 9 mg/kg or
less) stable dose for at least 2 weeks prior to baseline.
• Antibiotics (eg metronidazole, rifaximin) stable dose for at least 2 weeks prior to
baseline and during the study treatment period.
• Rectally administered formulation of corticosteroids or 5-ASA stable dose for at
least 2 weeks prior to baseline and during the study treatment period.
5. Subjects willing to use double contraception during the study treatment period and until completion of follow-up procedures:
• If the subject is a sexually active woman of childbearing potential, she and her male partner are required to simultaneously use 2 effective contraceptive methods as listed in Section 4.4.5.2 Female subjects who wish to use non-hormonal
contraception must have done so for at least 14 days prior to the first dose of study
medication.
• Non-vasectomized males with female partners of child bearing potential must be
willing to use a condom in addition to having their female partner use another form
of contraception.
6. Subjects who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.
7. Evidence of a signed and dated informed consent document(s) indicating that the subject has been informed of all pertinent aspects of the study. |
|
| E.4 | Principal exclusion criteria |
1. Diagnosis of indeterminate colitis, Ulcerative Colitis (UC), or clinical findings suggestive of UC.
2. Treatment naïve subjects diagnosed with Crohn’s Disease
3. Subjects receiving the following therapy:
• Azathioprine/6-Mercaptopurine, Methotrexate within 7 days prior to baseline.
• Cyclosporine, Mycophenolate, Tacrolimus within 4 weeks prior to baseline.
• Interferon therapy within 8 weeks prior to baseline.
• Anti-TNFα therapy within 8 weeks prior to baseline.
4. Subjects who are currently receiving natalizumab.
5. Subjects who have previously participated in any study of CP-690,550.
6. Subjects who have received any investigational drug or device within 3 months prior to baseline.
7. History of symptomatic obstructive strictures, an ostomy, extensive bowel resection or short bowel syndrome
8. History of bowel surgery within 6 months prior to baseline
9. Fecal culture indicating presence of pathogenic infection
10. Subjects likely to require any type of surgery within 8 weeks from screening
11. Known collection or abscess on MRI of the pelvis
12. Subjects on elemental diet used for treating Crohn's disease within 7 days from baseline
13. Subjects with evidence of hematopoietic disorders:
• Hemoglobin levels <9.0 g/dL or hematocrit <30% at screening visit or within the 3
months prior to baseline
• An absolute white blood cell (WBC) count of <3.0 x 109/L (<3000/mm3) or absolute
neutrophil count of <1.2 X 109/L (<1200/mm3) at screening visit or within the 3
months prior to baseline
• Thrombocytopenia, as defined by a platelet count <100 x 109/L (<100,000/mm3) at
screening visit or within the 3 months prior to baseline
14. Total bilirubin, AST or ALT more than 2 times the upper limit of normal at screening visit
15. Estimated GFR ≤50 ml/min based on Cockcroft-Gault calculation
16. Current or recent history of severe, progressive, or uncontrolled renal, hepatic,
hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, or neurological disease
17. Current immunization with any live virus vaccine or history of immunization with any live virus vaccine within 8 weeks of baseline
18. Current routine household contact with children who have received varicella or oral polio vaccine within 2 months prior to baseline or scheduled to receive vaccination during study treatment and follow up period
19. History of any lymphoproliferative disorder, history of lymphoma, leukemia, myeloproliferative disorders, multiple myeloma, or signs and symptoms suggestive of current lymphatic disease
20. Evidence of active or latent infection with Mycobacterium tuberculosis (TB), as defined by any of the following:
• A subject has a positive Mantoux Purified Protein Derivative skin test result
of ≥5 mm of induration within the 3 months prior to screening.
• A subject is immunoreactive for TB using an ex vivo method (eg QuantiFERON-TB
Gold (QFT Gold) or T-Spot test).
• A subject has a chest radiograph (taken within the 3 months prior to screening) that has changes suggestive of active TB infection.
21. Subjects with clinically significant infections currently or within 6 months of baseline (eg those requiring hospitalization or parenteral antimicrobial therapy or opportunistic infections), or those with a history of more than one episode of herpes zoster, a history of disseminated zoster, a history of any infection otherwise judged by the investigator to have the potential for exacerbation by participation in the study or any infection requiring antimicrobial therapy within 2 weeks of screening.
22. Any prior treatment with lymphocyte-depleting agents/therapies (such as
CamPath®[alemtuzab], alkylating agents [eg, cyclophosphamide or chlorambucil], total lymphoid irradiation, etc). Subjects who have received rituximab or other selective B lymphocyte depleting agents are eligible if they have not received such therapy for at least 1 year prior to baseline.
23. Subjects with any condition possibly affecting oral drug absorption eg gastrectomy, or clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric bypass. Procedures such as gastric banding, that simply divide the stomach into separate chambers, are NOT exclusionary.
24. Pregnant or lactating women.
25. History of alcohol or drug abuse with less than 6 months of abstinence prior to baseline.
26. Screening 12-lead ECG that demonstrates clinically relevant abnormalities which may affect subject safety or interpretation of study results.
27. Donation of blood in excess of 500 mL within 2 months prior to baseline.
28. Subjects with an oral or tympanic temperature of 38°C or higher at screening or baseline.
29. Subjects with a first-degree relative with a hereditary immunodeficiency.
30. Subjects with malignancies or with a history of malignancies with the exception of
adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Clinical response (Week 4) defined by a decrease in the Crohn’s disease activity index (CDAI) score of at least 70 points from baseline. |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Tolerability,Quality of Life |
|
| 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.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 50 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| 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 | |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 14 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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