Crohn’s Disease MedDRA version: 20.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Trade Name: STELARA®
Product Name: Ustekinumab
Product Code: CNTO1275
Pharmaceutical Form: Solution for injection in pre-filled syringe
Sponsors
Janssen-Cilag International N.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each potential participant must satisfy all the following criteria to be enrolled in the study: 1. Male or female aged =18 years (or the legal age of consent in the jurisdiction in which the study is taking place if older than 18 years). 2. A history of Crohn’s disease or fistulizing Crohn’s disease of at least 3 months’ duration, with colitis, ileitis, or ileocolitis, confirmed at any time in the past by radiography, histology, and/or endoscopy. 3. Initially responded to ustekinumab induction therapy (a), administered according to the local label, followed by secondary LoR to ustekinumab (b). a) Initial response to ustekinumab as defined in Section 10.2. b) Secondary LoR to ustekinumab is defined as active disease at study baseline, proven by a crohn’s disease activity index (CDAI) score of =220 and =450 with at least one of the following: - Elevated CRP (>3.0 milligram per litre [mg/L]); and/or - Elevated FeCa (>250 mg/kg); and/or - Endoscopy (performed within the 3 months before baseline) with evidence of active Crohn’s disease during the current disease flare (ie, ulcerations in the ileum and/or colon). 4. The following medications for the treatment of Crohn’s disease are permitted providing the doses indicated are stable for at least 3 weeks before baseline or have been discontinued at least 3 weeks before baseline: ? Oral 5-aminosalicylic acid (5-ASA) compounds. ? Oral corticosteroids (eg, prednisone, budesonide) at a prednisone-equivalent dose of =40 mg/day or =9 mg/day of budesonide. ? Antibiotics used as the primary treatment of Crohn’s disease. ? Any participants receiving conventional immunomodulators (ie, azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]) must have been taking them for =12 weeks and must have been on a stable dose for a least 4 weeks before baseline. 5. The following laboratory test results are within the specified limits at screening: ? Hemoglobin =8.5 g/dL (=85 g/L). ? White blood cell (WBC) count =3.5 x 10^3/µL (=3.5 GI/L). ? Neutrophils =1.5 x 10^3/µL (=1.5 GI/L). ? Platelets =100 x 10^3/µL (=100 GI/L). ? Serum creatinine <1.7 mg/dL (=133 µmol/L). ? Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase levels =2 times the upper limit of normal for the laboratory conducting the test. ? Direct (conjugated) bilirubin <1.0 mg/dL (<0.01 g/L). 6. Meet the following TB screening criteria: ? No history of latent or active TB before screening. An exception is made for participants who have a history of latent TB and are currently receiving treatment for latent TB, will initiate treatment for latent TB prior to first administration of study intervention, or have documentation of having completed appropriate treatment for latent TB within 5 years prior to the first administration of study intervention. It is the responsibility of the investigator to verify the adequacy of previous TB treatment and provide appropriate documentation. ? No signs or symptoms suggestive of active TB upon medical history and/or physical examination. ? No recen
Exclusion criteria
Exclusion criteria: 1.Complications of Crohn’s disease, such as symptomatic strictures or stenoses, short gut syndrome, or any other manifestation that might be anticipated to require surgery, could preclude the use of the CDAI 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 before baseline, or 8 weeks before baseline for intra-abdominal abscesses, provided there is no anticipated need for any further surgery. Participants with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses identified. 3.Any kind of bowel resection within 6 months or any other intra-abdominal surgery within 3 months before baseline. 4.A draining (ie, functioning) stoma or ostomy. 5.Received any of the following prescribed medications or therapies within the specified period: ?Any off-label use of ustekinumab, including additional IV re-induction or shortened frequency of subcutaneous dose administration, after the initial weight-tiered based IV induction dose of ustekinumab. ?Intravenous corticosteroids as a treatment for Crohn’s disease within 3 weeks before baseline. ?Oral immunomodulatory agents other than AZA, 6-MP, or MTX (eg, Janus kinase [JAK] inhibitors, 6-thioguanine [6-TG], cyclosporine, tacrolimus, sirolimus, tofacitinib, or mycophenolate mofetil) within 4 weeks before baseline. ?Any other investigational agent for Crohn’s disease (eg other biologics, small molecules or anti-sense RNA such as mongersen), unless at least 3 months or 5 half-lives (whichever is longer) have elapsed since the last dose. ?Treatment with apheresis (eg, Adacolumn apheresis) or total parenteral nutrition as a treatment for Crohn’s disease within 3 weeks before baseline. 6.A stool culture or other examination in the last 4 months that is positive for an enteric pathogen, including Clostridium difficile toxin, unless a repeat examination is negative and there are no signs of ongoing infection with that pathogen. 7.Received a Bacille Calmette-Guérin (BCG) vaccination within 12 months before baseline or any other live bacterial or live viral vaccination within 2 weeks before baseline. 8.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 nonremitting cystitis), or open, draining, or infected skin wounds or ulcers. 9.Any 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. 10.A history of serious infection (eg, sepsis, pneumonia, or pyelonephritis), including any infection requiring hospitalization or IV antibiotics, for 8 weeks before baseline. 11.Evidence of a herpes zoster infection =8 weeks before baseline. 12.A history of latent or active granulomatous infection, including histoplasmosis or coc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the achievement of clinical response at Week 16 following a single intravenous (IV) re-induction dose of ~6 milligram per kilogram (mg/kg) ustekinumab, compared with continuing regular subcutaneous (SC) dosing every 8 weeks (q8w) 90 milligram (mg) ustekinumab administration, in participants with secondary loss of response (LoR) to SC q8w 90 mg ustekinumab maintenance therapy.; Secondary Objective: The secondary objectives are to: ? Evaluate the achievement of clinical response and clinical remission, as well as the reduction in inflammatory biomarkers (serum C-reactive protein [CRP] and fecal calprotectin [FeCa] levels), after IV ustekinumab re-induction. ? Assess the overall safety of IV ustekinumab re-induction. ;Primary end point(s): The primary endpoint is clinical response at Week 16, defined as a =100-point reduction from the baseline CDAI score or a CDAI score <150 points.;Timepoint(s) of evaluation of this end point: At week 16 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Clinical remission at Week 16, defined as a CDAI score of <150 points. 2. Clinical response at Week 8, defined as a =100-point reduction from the baseline CDAI score or a CDAI score <150. 3. Clinical remission at Week 8, defined as a CDAI score of <150 points. 4. Normalization of CRP and/or FeCa concentration(s) at Week 16, among participants with an elevated CRP and/or FeCa at baseline. 5. Clinical remission at Week 24, defined as a CDAI score of <150 points. 6. Clinical response at Week 24, defined as a =100-point reduction from the baseline CDAI score or a CDAI score <150. 7. Normalization of CRP and/or FeCa concentration(s) at Week 24, among participants with an elevated CRP and/or FeCa at baseline. 8. Safety endpoints, including the proportion of participants with at least one adverse event and subcategories of adverse events (all infections, all serious adverse events and serious infections), as well as changes in vital signs and clinical laboratory test results. ; Timepoint(s) of evaluation of this end point: 1 & 4. At week 16 2 & 3. At week 8 5, 6 & 7. At week 24 8. Throughout the study (Screening to week 24 or early termination) | — |
Countries
France, Germany, Netherlands, Spain, Sweden, United States
Contacts
Public ContactGlobal Clinical Operations Spain
Janssen-Cilag. S.A.
Outcome results
None listed