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 |
|
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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011402 |
E.1.2 | Term | Crohn's disease (colon) |
E.1.2 | System Organ Class | 100000004856 |
|
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 of the study is to estimate the effects of tofacitinib in maintaining a clinical response or being in remission in subjects with moderate to severe Crohn’s disease previously achieving clinical response or remission in induction Study A3921083. |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the safety and tolerability of tofacitinib as a maintenance therapy in subjects with active Crohn’s disease.
• To estimate the effect of tofacitinib as a maintenance therapy on clinical remission, sustained remission and sustained response rates in subjects with Crohn’s disease.
• To evaluate the pharmacokinetics of tofacitinib as a maintenance therapy in subjects with moderate to severe Crohn’s disease.
• To evaluate the effect of tofacitinib as a maintenance therapy on quality of life in subjects with moderate to severe Crohn’s disease.
• To evaluate the effect of tofacitinib as a maintenance therapy on CRP and fecal calprotectin.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects who met study entry criteria, and who completed Week 8 visit of Induction Study A3921083.
2. Subjects who achieve clinical response-100 (reduction in CDAI by ≥ 100 points) and/or clinical remission (CDAI<150) in Study A3921083.
3. Women of childbearing potential must test negative for pregnancy prior to study enrolment.
4. Sexually active females of childbearing potential are required to use adequate contraceptive methods during the study period and until completion of the follow-up procedures. No specific contraceptive measures are required in male subjects during study participation (Further description of the requirements and a list of contraceptives considered effective and acceptable for use in this trial are found in Section 4.4 Life Style Guidelines).
5. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
6. Evidence of a personally signed and dated informed consent document(s) indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study. |
|
E.4 | Principal exclusion criteria |
1. Subjects who had major protocol violation (as determined by the Sponsor) in the A3921083 study. 2. Fecal culture/toxin assay indicating presence of pathogenic infection, unless the subject has completed a full course of treatment or, if treatment is ongoing, be clinically improved in the judgement of the investigator. 3. Presence of active (draining) fistulae, intrabdominal or perineal
collection or abscess (MRI imaging is not required for entry to this study unless clinically indicated). 4.Subjects with evidence of or suspected liver disease ie, liver injury due to methotrexate or primary sclerosing cholangitis. 5.Subjects with evidence of blood dyscrasias at baseline visit (as assessed by the laboratory results from Week 7 of A3921083): Hemoglobin levels <9.0 g/dL; An absolute white blood cell (WBC) count of <3.0 x 10 to the power of 9/L (<3000/mm3) or absolute neutrophil count of <1.2 X 10 to the power of 9/L (<1200/mm3) or an absolute lymphocyte count of <0.5 x 10 to the power of 9/L (<500/mm3); Thrombocytopenia, as defined by a platelet count <100 x 10 to the power of 9/L (<100,000/mm3). 6.Subjects who have been scheduled to receive any live or attenuated virus vaccination during study period and for 6 weeks after last dose of study drug. 7. Women who are pregnant or lactating, or planning pregnancy during the study period. 8. Subjects with estimated GFR≤ 40 mL/min based on Cockcroft-Gault calculation from Week 7 of the A3921083 study. 9. Subjects with total bilirubin, AST or ALT more than 1.5 times the upper limit of normal from Week 7 of the A3921083 study. 10.Subjects with current or recent history of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic (including uncontrolled hypercholesterolemia), endocrine, pulmonary, cardiac, or neurological disease. 11.Baseline 12-lead ECG that demonstrates clinically relevant abnormalities which may affect subject safety or interpretation of study results (i.e. baseline QTcF >450 ms, complete LBBB, acute or indeterminate age myocardial infarction, 2nd-3rd degree AV block, or serious bradyarrhythmias or tachyarrhythmias; see Appendix 3 of protocol) 12.Subjects who are expected to receive prohibited concomitant medications including medications that are either moderate to potent CYP3A4 inducers or inhibitors during the study period.
13.Subjects who, in the opinion of the investigator or Pfizer, will be uncooperative or unable to comply with study procedures. 14.Subjects who are investigational site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial. 15. Subjects who are participating in or interested in participating in other investigational studies during study A3921084. 16.Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of subjects maintaining clinical response-100, as defined by a decrease in CDAI score at least 100 points from A3921083 baseline, or being in clinical remission, as defined by a CDAI score less than 150, at Week 26. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The proportion of subjects maintaining clinical response-100, as defined by a decrease in CDAI score at least 100 points from A3921083 baseline, or being in clinical remission, as defined by a CDAI score less than 150, at week 26. |
|
E.5.2 | Secondary end point(s) |
• The proportion of subjects maintaining clinical response-100 or being in clinical remission at Weeks 4, 8, 12, 20 and 26 from the A3921083 Baseline.
• The proportion of subjects maintaining at least a clinical response-100 at Weeks 4, 8, 12, 20 and 26.
• The proportion of subjects in clinical remission at Weeks 4, 8, 12, 20 and 26.
• The proportion of subjects in clinical remission at Weeks 4, 8, 12, 20, and 26 among subjects in clinical remission at baseline of maintenance study.
• The proportion of subjects in sustained clinical remission in the maintenance phase. Sustained clinical remission is defined as being in clinical remission at both Weeks 20 and 26.
• The proportion of subjects achieving sustained clinical response in the maintenance phase. Sustained clinical response is defined as having at least a clinical response-100 at both Weeks 20 and 26 from the A3921083 Baseline.
• CDAI scores over time and CDAI scores change from Baseline.
• The time to relapse. Relapse is defined as increase in CDAI of >100 points from the maintenance phase baseline and a CDAI score of >220 points.
• The proportion of subjects achieving a steroid-free clinical remission at Week 26 of the maintenance phase among subjects on steroids at baseline.
• Serum CRP and fecal calprotectin over time and change from baseline in CRP and fecal calprotectin.
• Plasma concentrations of tofacitinib. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
See Secondary Endpoints in section E.5.2. above |
|
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 | Yes |
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 | 3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 49 |
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 | No |
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 |
Australia |
Austria |
Bulgaria |
Canada |
Croatia |
Czech Republic |
France |
Germany |
Greece |
Hungary |
Israel |
Japan |
Korea, Republic of |
Netherlands |
South Africa |
Spain |
Ukraine |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
End of Trial in all participating countries is defined as Last Subject Last Visit (LSLV). End of Trial in a Member State of the European Union is defined as the time at which it is deemed that sufficient subjects have been recruited and completed the study as stated in the regulatory application (ie, Clinical Study Application (CTA)) and ethics application in the Member State. |
|
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |