A Study of Guselkumab in Participants With Moderately to Severely Active Crohn's Disease
- Registration Number
- NCT04397263
- Lead Sponsor
- Janssen Pharmaceutical K.K.
- Brief Summary
The purpose of this study is to evaluate the safety of Guselkumab in participants with Crohn's disease.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 38
- Have Crohn's Disease (CD) or fistulizing CD of at least 3 months duration (defined as a minimum of 12 weeks), with colitis, ileitis, or ileocolitis, confirmed at any time in the past by radiography, histology, and/or endoscopy
- Have moderate to severe CD as assessed by CDAI components of stool frequency (SF), and abdominal pain (AP) scores, and endoscopic evidence
- Have screening laboratory test results within the protocol specified parameters
- A female participant of childbearing potential must have a negative urine pregnancy test result at screening and baseline
- Demonstrated intolerance or inadequate response to conventional or to biologic therapy for CD
- Has complications of CD, such as symptomatic strictures or stenoses, short gut syndrome, or any other manifestation
- Unstable doses of concomitant Crohn's disease therapy
- Receipt of Crohn's disease approved biologic agents, investigational agents, or procedures outside of permitted time frame as specified in the protocol
- Prior exposure to p40 inhibitors or p19 inhibitors
- Any medical contraindications preventing study participation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Guselkumab Guselkumab Participants will receive guselkumab by intravenous (IV) infusion, followed by guselkumab by subcutaneous (SC) injection. Participants who are eligible and willing to continue guselkumab may enter the Long-term extension (LTE) phase and continue to receive guselkumab.
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) From baseline (Week 0) up to Week 48 Number of participants with TESAEs were reported. TEAEs are AEs with onset during the intervention phase or that are a consequence of a pre-existing condition that had worsened since baseline. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) From baseline (Week 0) up to Week 48 Number of participants with TEAEs were reported. An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Treatment-emergent AEs (TEAEs) were AEs with onset during the intervention phase or that were a consequence of a pre-existing condition that had worsened since baseline. All TEAEs including serious and non-serious AEs were reported.
Number of Participants With Treatment-emergent Adverse Events of Special Interest (TEAESI) From baseline (Week 0) up to Week 48 Number of participants with TEAESI was reported. Active tuberculosis (TB) or malignancies were considered as TEAESIs. TEAESIs were AESIs with onset during the intervention phase or that are a consequence of a pre-existing condition that had worsened since baseline.
Number of Participants With TEAEs of Infections From baseline (Week 0) up to Week 48 Number of participants with TEAEs of infections were reported. TEAEs are AEs with onset during the intervention phase or that are a consequence of a pre-existing condition that had worsened since baseline.
Number of Participants With Treatment-emergent Abnormalities in Hematology Laboratory Parameters From baseline (Week 0) up to Week 48 Number of participants with treatment-emergent abnormalities in hematology laboratory parameters were reported. Laboratory tests included in hematology were hemoglobin, lymphocytes, neutrophils, platelet count, Total WBC (white blood cell) Count. National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) toxicity grades were Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Potentially Life-Threatening). TE abnormalities are laboratory abnormalities with onset during the intervention phase or that are a consequence of a pre-existing condition that had worsened since baseline.
Number of Participants With TEAEs of Injection-site Reactions From baseline (Week 0) up to Week 48 Number of participants with TEAEs of injection-site reactions were reported. A significant injection-site reaction was defined as an adverse reaction that was manifested through 1 or more of the following symptoms: significant bruising, erythema, hemorrhage, irritation, pain, pruritus at the site of injection. TEAEs are AEs with onset during the intervention phase or that are a consequence of a pre-existing condition that has worsened since baseline.
Number of Participants With TEAEs Temporally Associated With Infusion From baseline (Week 0) up to Week 48 Number of participants with TEAEs temporally associated with infusion were reported. TEAEs are AEs with onset during the intervention phase or that are a consequence of a preexisting condition that had worsened since baseline.
Number of Participants With Treatment-emergent Abnormalities in Chemistry Laboratory Parameters From baseline (Week 0) up to Week 48 Number of participants with treatment-emergent abnormalities in chemistry laboratory parameters were reported. Laboratory parameters included in clinical chemistry were albumin, corrected calcium, creatinine, glucose, potassium, sodium. NCI-CTCAE) toxicity grades were Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Potentially Life-Threatening). TE abnormalities are laboratory abnormalities with onset during the intervention phase or that are a consequence of a pre-existing condition that had worsened since baseline.
Number of Participants With TEAEs of Suicidal Ideation, Suicidal Behavior, or Self-Injurious Behavior Without Suicidal Intent From baseline (Week 0) up to Week 48 TEAEs are AEs with onset during the intervention phase or that are a consequence of a pre-existing condition that had worsened since baseline. The Columbia-suicide severity rating scale (C-SSRS) defined was 5 subtypes of suicidal ideation and 4 possible suicidal behaviors, as well as non-suicidal self-injurious behavior and completed suicide. The C-SSRS was an investigator-administered questionnaire: 1) No suicidal ideation or behaviors (including self-injurious behavior without suicidal intent): No further action was needed; 2) Suicidal ideation levels 1-3 or non-suicidal self-injurious behavior; participant risk is assessed by the investigator. 3) Suicidal ideation levels 4 or 5 or any suicidal behavior: participant risk assessed and referral to a mental health professional. If no events qualify for scores of 1 to 10, score of 0 was assigned (0= "no event that can be assessed on the basis of C-SSRS"). Higher scores indicated greater severity.
Number of Participants With Clinically Significant Treatment-emergent Abnormalities in Vital Signs From baseline (Week 0) up to Week 48 Number of participants with clinically significant treatment-emergent abnormalities in vital signs were reported. Vital signs included weight, pulse rate, temperature, respiratory rate, systolic blood pressure, and diastolic blood pressure. TEAEs are AEs with onset during the intervention phase or that are a consequence of a pre-existing condition that had worsened since baseline.
Number of Participants With Concomitant Medications for Crohn's Disease From screening (Week -8) up to Week 48 Number of participants with concomitant medications for Crohn's disease were reported.
- Secondary Outcome Measures
Name Time Method Number of Participants With Neutralizing-Guselkumab Antibodies Through Week 48 From Week 0 through Week 48 Number of participants with neutralizing-guselkumab antibodies through Week 48 were reported.
Change From Baseline in Inflammatory PD Marker: Fecal Calprotectin (FC) Levels Baseline (Week 0), Weeks 4, 8, 12, 24, and 48 Change from baseline in inflammatory PD marker of FC levels were reported.
Number of Participants With Clinical Remission Through Week 48 Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 Number of participants with clinical remission through Week 48 were reported. Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score \<150. The multi-item CDAI score assessed severity of illness by collecting information on 8 different Crohn's disease-related variables (extraintestinal manifestations, abdominal mass, weight, hematocrit, use of antidiarrheal drug(s) and/or opiates, total number of liquid or very soft stools, abdominal pain/cramps, and general well-being). The last 3 variables were scored over 7 days by the participant on a diary card. The total CDAI score ranged from 0 (improvement in disease activity) to 600 (more disease activity) in general: higher score indicated higher disease activities and a decrease in total CDAI score over time indicated improvement in disease activity.
Number of Participants With Clinical Response Through Week 48 Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 Number of participants with clinical response through Week 48 were reported. Clinical response was defined as a greater than or equal to (\>=) 100-point reduction from baseline in CDAI score or CDAI score less than \<150. The multi-item CDAI score assessed severity of illness by collecting information on 8 different Crohn's disease-related variables (extraintestinal manifestations, abdominal mass, weight, hematocrit, use of antidiarrheal drug(s) and/or opiates, total number of liquid or very soft stools, abdominal pain/cramps, and general well-being). The last 3 variables were scored over 7 days by the participant on a diary card. The total CDAI score ranged from 0 (improvement in disease activity) to 600 (more disease activity) in general: higher score indicated higher disease activities and a decrease in total CDAI score over time indicated improvement in disease activity.
Number of Participants With Anti-Guselkumab Antibodies Through Week 48 From Week 0 through Week 48 Number of participants with anti-guselkumab antibodies through Week 48 were reported.
Number of Participants With Patient-reported Outcome(s) (PRO)-2 Remission Through Week 48 Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 Number of participants with PRO-2 remission through Week 48 were reported. PRO-2 remission was defined as abdominal pain (AP) mean daily score at or below 1 and stool frequency (SF) mean daily score at or below 3, and no worsening of AP or SF from baseline. Mean daily AP score was defined as the sum of abdominal pain/cramps ratings in the previous 7 days in a diary card divided by the total number of days assessments were performed. Average daily SF score was defined as the sum of number of liquid or very soft stools in the previous 7 days in a diary card divided by the total number of days assessments were performed. Mean daily SF and AP scores score at a scheduled visit were not calculated if total number of days of assessment was less than 5. Higher PRO-2 scores indicated more severe disease.
Serum Concentation of Guselkumab Predose at Weeks 0, 4, 8, 12, 16, 20, 24, 32, 40, 48 and 1 hour post dose at Weeks 0, 4, 8 Serum concentration of guselkumab were reported.
Change From Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) Score at Week 48 Baseline (Week 0) and Week 48 Change from baseline in SES-CD score at Week 48 were reported. The SES-CD score was used to evaluate endoscopic improvement. The SES-CD was based on the evaluation of 4 endoscopic components (presence/size of ulcers, proportion of mucosal surface covered by ulcers, proportion of mucosal surface affected by any other lesions, and presence/type of narrowing/strictures) across 5 ileocolonic segments. Each endoscopic component was scored from 0 (best) to 3 (worst) for each segment, resulting in a total score of up to 15 for each component, except for the narrowing component which only attain a maximum total score of 11 because, the presence of a narrowing that cannot be passed can be only observed once. The total SES-CD score was the sum of all the component scores across all the segments and it ranged from 0 (best) to 56 (worst), where higher scores indicated more severe disease.
Change From Baseline in Crohn's Disease Activity Index (CDAI) Score at Week 48 by Serum Guselkumab Concentration Quartiles at Week 48 At Week 48 Change from baseline in CDAI score at Week 48 by serum guselkumab concentration quartiles at Week 48 were reported. The multi-item CDAI score assessed severity of illness by collecting information on 8 different Crohn's disease-related variables (extraintestinal manifestations, abdominal mass, weight, hematocrit, use of antidiarrheal drug(s) and/or opiates, total number of liquid or very soft stools, abdominal pain/cramps, and general well-being). The last 3 variables were scored over 7 days by the participant on a diary card. The total CDAI score ranged from 0 (improvement in disease activity) to 600 (more disease activity) in general: higher score indicated higher disease activities and a decrease in total CDAI score over time indicated improvement in disease activity.
Change From Baseline in Inflammatory Pharmacodynamic (PD) Marker: C-reactive Protein (CRP) Concentration Baseline (Week 0), Weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48 Change from baseline in inflammatory PD marker of CRP concentration were reported.
Number of Participants in Clinical Response at Week 48 by Serum Guselkumab Concentration Quartiles at Week 48 At Week 48 Number of participants in clinical response at Week 48 by serum guselkumab concentration quartiles at Week 48 were reported. Clinical response was defined as a \>=100-point reduction from baseline in CDAI score or CDAI score \<150. The multi-item CDAI score assessed severity of illness by collecting information on 8 different Crohn's disease-related variables (extraintestinal manifestations, abdominal mass, weight, hematocrit, use of antidiarrheal drug(s) and/or opiates, total number of liquid or very soft stools, abdominal pain/cramps, and general well-being). The last 3 variables were scored over 7 days by the participant on a diary card. The total CDAI score ranged from 0 (improvement in disease activity) to 600 (more disease activity) in general: higher score indicated higher disease activities and a decrease in total CDAI score over time indicated improvement in disease activity.
Number of Participants in Clinical Remission at Week 48 by Serum Guselkumab Concentration Quartiles at Week 48 At Week 48 Number of participants in clinical remission at Week 48 by serum guselkumab concentration quartiles at Week 48 were reported. Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score \<150. The multi-item CDAI score assessed severity of illness by collecting information on 8 different Crohn's disease-related variables (extraintestinal manifestations, abdominal mass, weight, hematocrit, use of antidiarrheal drug(s) and/or opiates, total number of liquid or very soft stools, abdominal pain/cramps, and general well-being). The last 3 variables were scored over 7 days by the participant on a diary card. The total CDAI score ranged from 0 (improvement in disease activity) to 600 (more disease activity) in general: higher score indicated higher disease activities and a decrease in total CDAI score over time indicated improvement in disease activity.
Number of Participants in Endoscopic Response at Week 48 by Serum Guselkumab Concentration Quartiles at Week 48 At Week 48 Number of participants in endoscopic response at Week 48 by serum guselkumab concentration quartiles at Week 48 were reported. Endoscopic response was defined as \>=50 % improvement from baseline in SES-CD score or SES-CD score less than or equal to (\<=) 2. The SES-CD was based on evaluation of 4 endoscopic components (presence/size of ulcers, proportion of mucosal surface covered by ulcers, proportion of mucosal surface affected by any other lesions, and presence/type of narrowing/strictures) across 5 ileocolonic segments. Each endoscopic component was scored from 0 (best) to 3 (worst) for each segment, resulting in a total score of up to 15 for each component, except for narrowing component which only attain a maximum total score of 11 because, presence of a narrowing that cannot be passed can be only observed once. The total SES-CD score was sum of all component scores across all segments and it ranged from 0 (best) to 56 (worst), where higher scores indicated more severe disease.
Number of Participants in Endoscopic Remission at Week 48 by Serum Guselkumab Concentration Quartiles at Week 48 At Week 48 Number of participants in endoscopic remission at Week 48 by serum guselkumab concentration quartiles at Week 48 were reported. Endoscopic remission: an SES-CD score \<= 4 with at least a 2-point reduction from baseline and no sub score \>1 in any individual subcomponent. The SES-CD was based on evaluation of 4 endoscopic components (presence/size of ulcers, proportion of mucosal surface covered by ulcers, proportion of mucosal surface affected by any other lesions, and presence/type of narrowing/strictures) across 5 ileocolonic segments. Each endoscopic component was scored from 0 (best) to 3 (worst) for each segment, resulting in total score of 15 for each component, except for narrowing component which only attain a maximum total score of 11 because, presence of a narrowing that cannot be passed can be only observed once. The total SES-CD score was sum of all component scores (all segments) \& it ranged from 0 (best) to 56 (worst), where higher scores indicated more severe disease.
Change From Baseline in the Average Daily Prednisone-equivalent (P.Eq) Oral Corticosteroid Dose (Excluding Budesonide) Through Week 48 Among Participants Receiving Oral Corticosteroids Other Than Budesonide at Baseline Baseline (Week 0), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 Change from baseline in the average daily P.Eq oral corticosteroid dose (excluding Budesonide) through Week 48 among participants receiving oral corticosteroids other than Budesonide at baseline were reported.
Number of Participants Not Receiving Concomitant Corticosteroids at Week 48 Among Participants Receiving Concomitant Corticosteroids at Baseline At Week 48 Number of participants not receiving concomitant corticosteroids at Week 48 among participants receiving concomitant corticosteroids at baseline were reported.
Number of Participants Not Receiving Concomitant Corticosteroids for at Least 30 Days Prior to Week 48 Among Participants Receiving Concomitant Corticosteroids at Baseline Up to Week 48 Number of participants not receiving concomitant corticosteroids for at least 30 days prior to Week 48 among participants receiving concomitant corticosteroids at baseline were reported.
Number of Participants Not Receiving Concomitant Corticosteroids for at Least 90 Days Prior to Week 48 Among Participants Receiving Concomitant Corticosteroids at Baseline Up to Week 48 Number of participants not receiving concomitant corticosteroids for at least 90 days prior to Week 48 among participants receiving concomitant corticosteroids at baseline were reported.
Trial Locations
- Locations (25)
Hitachi General Hospital
🇯🇵Hitachi, Japan
KOKIKAI Tokatsu Tsujinaka Hospital
🇯🇵Abiko, Japan
Institute of Science Tokyo Hospital
🇯🇵Bunkyo ku, Japan
Asahikawa Medical University Hospital
🇯🇵Hokkaido, Japan
Ofuna Chuo Hospital
🇯🇵Kamakura, Japan
Kishiwada Tokushukai Hospital
🇯🇵Kishiwada, Japan
Kumamoto University Hospital
🇯🇵Kumamoto, Japan
Japanese Red Cross Kumamoto Hospital
🇯🇵Kumamoto, Japan
Kyorin University Hospital
🇯🇵Mitaka, Japan
Kenseikai Dongo Hospital
🇯🇵Nara, Japan
Hyogo Medical University Hospital
🇯🇵Nishinomiya shi, Japan
Ishida Clinic of IBD and Gastroenterology
🇯🇵Oita, Japan
Okayama University Hospital
🇯🇵Okayama-shi, Japan
Kitasato University Hospital
🇯🇵Sagamihara, Japan
Saga University Hospital
🇯🇵Saga, Japan
Saitama Medical Center
🇯🇵Saitama, Japan
Sapporo Tokushukai Hospital
🇯🇵Sapporo, Japan
Sendai Kosei Hospital
🇯🇵Sendai Miyagi, Japan
Jichi Medical University Hospital
🇯🇵Shimotsuke, Japan
Tokyo Women's Medical University Hospital
🇯🇵Shinjuku-ku, Japan
Tokyo Metropolitan Bokutoh Hospital
🇯🇵Sumida ku, Japan
Osaka Medical and Pharmaceutical University Hospital
🇯🇵Takatsuki, Japan
Center Hospital of the National Center for Global Health and Medicine
🇯🇵Tokyo, Japan
Toyama Prefectural Central Hospital
🇯🇵Toyama, Japan
National Hospital Organization Toyohashi Medical Center
🇯🇵Toyohashi, Japan