Treatment of Crohn's disease with Ustekinumab in clinical practice
- Conditions
- Crohn's diseaseMedDRA version: 20.0Level: PTClassification code 10011401Term: Crohn's diseaseSystem Organ Class: 10017947 - Gastrointestinal disordersTherapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2017-005151-83-DE
- Lead Sponsor
- Charité Universitätsmedizin Berlin
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 60
1. Male or female =18 years of age
2. Have active, moderate to severe, ileal and/or colonic CD, demonstrated by: HBI score of = 5 at Baseline; Endoscopy with evidence of active CD (defined as SES-CD score =3 excluding the contribution of the narrowing component score) obtained within the 2-week screening period. A prior endoscopy may be used only if obtained within 3 months prior to baseline (Week 0), in which case the prior endoscopy must be centrally read again and SES-CD calculated based on this second, centralized read-out.
3. Has had an inadequate response with, lost response to, was intolerant to, or had medical contraindications to one or more previous biologic therapies approved for the treatment of CD in Germany (ie, infliximab, adalimumab or vedolizumab) or had an inadequate response to conventional therapy (no biological treatment).
4. Adhere to the following requirements for concomitant medication for the treatment of CD. The following medications are permitted provided doses meeting the requirements below are stable for or have been discontinued at least 3 weeks prior to baseline (Week 0), unless otherwise specified:
a. Oral 5-aminosalicylic acid (5-ASA) compounds; b. Oral corticosteroids (eg, prednisone, budesonide) at a prednisone-equivalent dose of =40 mg/day or =9 mg/day of budesonide. Subject must be willing to taper corticosteroids; c. Antibiotics being used as a primary treatment of CD; d. Conventional immunomodulators (ie, azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]). Subjects must have been taking them for=12 weeks, and on a stable dose for a least 4 weeks prior to baseline.
5. Are eligible according to tuberculosis (TB) infection screening criteria.
6. Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.
7. A woman of childbearing potential must have a negative highly sensitive serum (ß -human chorionic gonadotropin [ß-hCG]) pregnancy test at screening, and a negative urine pregnancy test at Week 0.
8. Contraceptive use by men or women should be consistent with German Federal or State regulations regarding the use of contraceptive methods for subjects participating in clinical studies. Before inclusion, a woman must be either: a. Not of childbearing potential defined as: Premenarchal; Postmenopausal (A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level) (>40 IU/L or mIU/mL) in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy, however in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. Permanently sterile (Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy.)
b. Of childbearing potential and: practicing a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly). Examples of highly effective contraceptives included in protocol (page 27); agrees to remain on a highly effective method throughout the study and for at least 15 weeks after the last dose of ustekinumab. Note: If the childbearing potential changes after the start of the study or the risk of pregnancy changes (eg, a woman who is not het
1. Has complications of CD such as symptomatic strictures or stenoses, short bowel syndrome, or any other manifestation that might be anticipated to require immediate surgery, could preclude the use of the HBI to assess response to therapy, or would possibly confound the ability to assess the effect of treatment with ustekinumab.
2. Currently has or is suspected to have an abscess. Recent cutaneous and perianal abscesses are not exclusionary if drained and adequately treated at least 3 weeks prior to baseline, or 8 weeks prior to baseline for intra-abdominal abscesses, provided there is no anticipated need for any further surgery. Subjects with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses identified.
3. Has previously received a biologic agent targeting IL-12 and/or IL-23, including but not limited to ustekinumab.
4. Has received any of the following prescribed medications or therapies within the specified period: a. Non-autologous stem cell therapy or biologic agents that deplete B or T cells <12 months prior to baseline.
b. Any investigational drug within 4 weeks before first administration of ustekinumab or within 5 half-lives of the investigational drug, whichever is longer.
5. Has received a Bacille Calmette-Guérin (BCG) vaccination within 12 months or any other live bacterial or live viral vaccination within 12 weeks of baseline.
6. Have a stool culture or other examination positive for an enteric pathogen, including Clostridium difficile toxin, in the last 4 months unless a repeat examination is negative and there are no signs of ongoing infection with that pathogen.
7. Has a history of, or ongoing, chronic or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection, recurrent urinary tract infection (eg, recurrent pyelonephritis or chronic non-remitting cystitis), or open, draining, or infected skin wounds or ulcers.
8. Has current signs or symptoms of infection. Established non-serious infections (eg, acute upper respiratory tract infection, simple urinary tract infection) need not be considered exclusionary at the discretion of the investigator.
9. Has a history of serious infection (eg, sepsis, pneumonia, or pyelonephritis), including any infection requiring hospitalization or IV antibiotics, for 8 weeks prior to baseline.
10. Has any contraindication according to the German ustekinumab label.
11. Has evidence of a herpes zoster infection =8 weeks prior to baseline.
12. Has a history of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, prior to screening. Refer to inclusion criteria for information regarding eligibility with a history of latent TB.
13. Has evidence of current active infection, including TB, or a nodule suspicious for lung malignancy on screening or any other available chest radiograph, unless definitively resolved surgically or by additional imaging and with source document confirmation.
14. Has or ever has had a nontuberculous mycobacterial infection or serious opportunistic infection (eg, cytomegalovirus colitis, Pneumocystis carinii, aspergillosis).
15. Is known to be infected with HIV, hepatitis B, or hepatitis C. Testing at screening is mandatory and must be documented.
16. Has severe, progressive, or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, neurologic, cerebral, or p
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method