The primary objective of the study is to assess the safety and tolerability of long-term open-label CP-690,550 therapy in subjects with CD.Secondary objectives are to evaluate the effect of CP-690,550 maintenance therapy on clinical remission and on…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety
* Incidence and severity of adverse events, clinical laboratory abnormalities,
and change from baseline in clinical laboratory values
Efficacy
* As this is an open-label extension study, there will be no primary efficacy
endpoint. All efficacy endpoints will be exploratory. Sustained clinical
remission is defined as being in clinical remission at both Week 24 and Week 48
Health Outcome
* Absolute scores and change from baseline in Inflammatory Bowel Disease
Questionnaire (IBDQ) Total score and domain scores (Bowel Symptoms, Systemic
Symptoms, Emotional Function and Social Function) over time
Secondary outcome
Safety
* Incidence of clinically significant changes in physical examination from
baseline
Efficacy
* The proportion of all enrolled subjects in clinical remission and sustained
clinical remission at Week 48
* The proportions of subjects in clinical remission and sustained clinical
remission among subjects in clinical remission at A3921086 baseline
* The proportion of subjects in clinical remission and sustained clinical
remission among subjects in clinical response (CDAI-100 response from Study
A3921083 baseline) or clinical remission at A3921086 baseline
Health Outcome
* The proportion of subjects with IBDQ total score *170 at Week 48 (clinical
remission)
* The absolute scores for the Patient-Reported Treatment Impact Assessment
(PRTI) at Week 48
For further information about safety, efficacy and health outcome secondary
study parameters, see the protocol section 2 *study objectives and endpoints*.
Background summary
CP-690,550 is being developed for the treatment of adult patients with
moderate-to-severe Crohn*s disease. At present, no current pharmacological
therapy provides a cure for Crohn*s disease, and the treatment goal is to
induce and then maintain remission. Despite available current treatment
options, there is still a large unmet medical need with many patients failing
to achieve clinical remission or experiencing apparent loss of initial efficacy
with continued use. Surgery remains a treatment option of last resort, but is
not curative and often is followed by disease recurrence. Thus, the need exists
for a novel and more effective treatment for Crohn*s disease, with more
convenient route of administration.
The clinical development program for CP-690,550 includes healthy volunteers and
patients with Crohn*s disease and other diseases enrolled in 52 Phase 1, 2, and
3 studies; potentially important safety risks have been observed with the oral
use of CP-690,550 in humans. It is not anticipated that treatment with
CP-690,550 in CD patients will have new significant safety risks. However, the
primary objective of the study is to assess the safety and tolerability of
long-term open-label CP-690,550 therapy in subjects with CD. Please see chapter
1 of the protocol (introduction) for more details.
Study objective
The primary objective of the study is to assess the safety and tolerability of
long-term open-label CP-690,550 therapy in subjects with CD.
Secondary objectives are to evaluate the effect of CP-690,550 maintenance
therapy on clinical remission and on quality-of-life in subjects with CD, and
also on biomarkers as measured by CRP and fecal calprotectin.
Study design
The patients participate in the study for approximately 1 year on average.
During this period, the patient will visit the hospital 7 times (every 8 to 12
weeks). During these visits the following procedures will be performed:
* Discuss medical history, treatment and drug use complaints
* Measurement of blood pressure, pulse, temperature and weight and further
physical examination
* Blood tests (around 10 ml withdrawn each time)
* Urine- and fecal analysis to assess the general health status
* Pregnancy test (if applicable)
* ECG (electrocardiogram)
* Completion of questionnaires on health, quality of life and daily activities
Four weeks after treatment, there is a final visit.
Intervention
* Oral intake of CP-690,550 5 mg or CP-690,550 10 mg study medication, in the
form of CP-690,550 5 mg tablets
* Laboratory assessments (blood, urine and feces)
* Questionnaires
Study burden and risks
All medicines have side effects, as well as CP-690,550. Side effects often
disappear when the drug is stopped. They can also remain for a longer period or
permanently. Side effects can be mild, but also severe and even life
threatening. Also, there may be not previously reported, potentially serious,
side effects. Furthermore, the patient may also experience an allergic reaction
to the drug.
Most frequently mentioned side effects are: bowel complaints (nausea, diarrhea,
constipation, and stomach ache), headache, fever, fatigue and upper respiratory
inflammations.
Also less frequent side effects can be present, for example inflammations,
decline in white blood cells or increased cholesterol values.
Risk of procedures involved in this trial
Blood withdrawal: these risks include fainting, inflammation of the vein, pain,
hemorrhage or a bleeding at the site of puncture. Also a small risk on
inflammation is present
ECG: irritation of the skin or a rash of the gel/stickers used
Staying sober: a patient may experience dizziness, headache or stomach aches
and could faint
Questionnaires: these may contain sensitive questions
The available data on the potential and identified risks of CP-690,550 are thus
considered to not preclude clinical studies in Crohn*s disease patients and the
risks are minimized through appropriate pre-enrolment screening and close
safety monitoring. Therefore, the overall risk-benefit assessment for this
study is considered to be favourable.
Arcola Road 500
Collegeville, PA 19426
US
Arcola Road 500
Collegeville, PA 19426
US
Listed location countries
Age
Inclusion criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:;
1. Subjects who complete 26-week maintenance treatment of the A3921084 study or subjects who withdraw early due to A3921084 study treatment failure;
2. Women of childbearing potential must test negative for pregnancy prior to study enrolment.;
3. 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.;
4. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.;
5. 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.
Exclusion criteria
Subjects presenting with any of the following will be excluded from the study:;
1. Subjects who have been discontinued due to protocol violation(s) (as determined by the Sponsor) in the A3921084 study.;
2. Subjects who were discontinued from the A3921084 study due to an adverse event that was not related to Crohn's disease.;
3. Evidence of active (draining) fistulae, intrabdominal or perineal collection or abscess at Baseline (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 26 or early discontinuation visit from the A3921084 study):;
* 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 absolute lymphocyte count of <0.5 x 109/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 breastfeeding, or planning pregnancy during the study period.;
8. Subjects with estimated GFR *40 mL/min based on Cockcroft-Gault calculation from Week 26 or early discontinuation visit from the A3921084 study.;
9. Subjects with total bilirubin, AST or ALT more than 1.5 times the upper limit of normal from Week 26 or early discontinuation visit from the A3921084 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 (from Week 26 or early discontinuation visit from the A3921084 study) that demonstrates clinically relevant abnormalities which may affect subject safety or interpretation of study results (ie, baseline QTcF >450 ms, complete LBBB, acute or indeterminate age myocardial infarction, 2nd-3rd degree AV block, or serious bradyarrhythmias or tachyarrhythmias).;
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 relatives of those site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial.;
15. 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.
16. Subjects who are participating in or interested in participating in other investigational
studies during study A3921086.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-003622-27-NL |
| ClinicalTrials.gov | NCT01470599 |
| CCMO | NL39793.091.12 |