Open-Label Extension and Safety Study for Participants With Crohn's Disease Previously Enrolled in the Etrolizumab Phase III Study GA29144
- Registration Number
- NCT02403323
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This open-label extension and safety monitoring study is composed of two parts: Part 1 will evaluate the long-term safety and efficacy of continued etrolizumab treatment in participants with moderately to severely active Crohn's disease who were previously enrolled in the etrolizumab Phase III Study GA29144 (NCT02394028) and who meet eligibility criteria for enrollment into Part 1. In Part 2, participants who have stopped etrolizumab treatment (either by exiting Part 1 of this study or by entering directly from Study GA29144 \[NCT02394028\]) will be monitored for 92 weeks for progressive multifocal leukoencephalopathy (PML) and other safety events.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 790
Part 1 Open-Label Extension:
- Patients previously enrolled in etrolizumab Phase III study GA29144 (NCT02394028) who meet the eligibility criteria for open-label etrolizumab as described in the protocol
Part 2 Safety Monitoring:
- Patients who participated in etrolizumab Phase III study GA29144 (NCT02394028) and are not eligible or choose not to enter Part 1
- Patients who transfer from Part 1
- Completion of the 12-week safety follow-up period prior to entering
Part 1 Open-Label Extension:
- Any new, significant, uncontrolled condition
Part 2 Safety Monitoring:
- No exclusion criteria
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Part 1: Etrolizumab Open-Label Extension Etrolizumab Participants will receive open-label treatment with etrolizumab once every 4 weeks until commercial availability in their country or sponsor's decision to terminate the study, whichever is earlier (up to approximately 10 years after the first patient is enrolled).
- Primary Outcome Measures
Name Time Method Part 1: Number of Participants With Crohn's Disease Activity Index (CDAI) Remission at 12-week Intervals Day 1 and Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240 and 252 of OLE CDAI is a score obtained from composite of eight assessments: number of liquid or soft stools, abdominal pain, general well-being, presence of complications, taking lomotil (diphenoxylate/atropine) or other opiates for diarrhea, presence of an abdominal mass, hematocrit, and percentage deviation from standard weight. A decrease in CDAI over time indicates improvement in disease activity. CDAI scores range from 0 to 600. A higher score indicates worse outcome. A total score of less than 150 corresponds to remission.
Part 1: Number of Participants With Clinical Remission at 12-week Intervals Day 1 and Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240 and 252 of OLE Clinical remission was defined as a liquid/soft stool frequency (SF) mean daily score ≤3 and an abdominal pain (AP) mean daily score ≤1 with no worsening in either subscore compared to baseline, where the average was taken over 7 days prior to visit. Abdominal pain severity was assessed using the abdominal pain questionnaire which is an 11-point numeric rating scale with score ranging from 0 (no pain) to 10 (worse pain). Liquid/soft stool frequency was reported using the bristol stool form scale which classifies stools into seven groups based on its consistency i.e., type 1- separate hard lumps, type 2- sausage-shaped but lumpy, type 3- like a sausage but with cracks on the surface, type 4- like a sausage or snake, smooth and soft, type 5- soft blobs with clear-cut edges, type 6- fluffy pieces with ragged edges and type 7- entirely liquid with no solid pieces.
Part 1: Number of Participants With Improvement in Simple Endoscopic Score for Crohn's Disease (SES-CD) Score at Week 108 At OLE Week 108 SES-CD is an endoscopic score composite of 4 variables (ulcers size, percentage of ulcerated surface, inflamed surface, and presence of narrowing) in up to 5 ileocolonic segments (ileum right, colon, transverse colon, left colon, rectum) and scored on a scale of 0-3, with total score from 0-60. Higher score indicates higher ulcer surface/size in the 4 variables. Endoscopic improvement was defined as ≥50% reduction in SES-CD score compared to baseline.
Part 1: Number of Participants With Adverse Event (AE) and Severity of AEs as Assessed Using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) From Day 1 up to end of 12-week safety follow-up in OLE (approximately 6.3 years) An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. AEs were graded as per NCI CTCAE v4.0. Grade 1=Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated; Grade 2=Moderate; minimal, local or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3=Severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4=Life threatening consequences, urgent intervention indicated; Grade 5=Death related to AE. Multiple occurrences of AEs in the same category at the worst (highest) NCIC-CTCAE grade for an individual are counted only once.
Part 1: Number of Participants With Serious Adverse Events (SAEs) From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years) An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and regardless of causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigation, whether or not considered related to the medicinal (investigational) product. A SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/ incapacity, is a congenital anomaly/ birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above.
Part 1: Number of Participants With Infection Related AEs and Severity of Infection-Related AEs Assessed Using NCI CTCAE v4.0 From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years) AE=untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with this treatment. AEs were graded per NCI CTCAE v4.0. Grade 1=Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated; Grade 2=Moderate; minimal, local or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3=Severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living; Grade 4=Life-threatening consequences/urgent intervention indicated; Grade 5=Death related to adverse event. If a participant experienced multiple occurrences of AEs at different grades, they were counted in each grade where they had at least one AE of that grade.
Part 1: Incidence Rate of Infection-related Adverse Event From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years) An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. AE rate (per 100 participant years) = \[Total number of AEs (in OLE only) / Total number of participant years at risk (in OLE only)\]\*100. Total participant-years at risk is the sum over all participants of the time intervals (in years) from the first dose of study treatment in Part 1 (OLE) until the participant completes/withdraws from the study (including the 12-week safety follow-up, if applicable).
Part 1: Number of Participants With Serious Infection Related AES From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years) An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and regardless of causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigation, whether or not considered related to the medicinal (investigational) product. A SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/ incapacity, is a congenital anomaly/ birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above.
Part 1: Number of Participants With Injection Site Reactions and Severity of Injection Site Reactions Assessed Using NCI CTCAE v4.0 From Day 1 up to end of safety 12-week follow-up in OLE (approximately 6.3 years) AE=untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with this treatment. AE can therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. Injection-site reaction=any local reaction occurring at the site of injection following study drug administration. Signs (e.g., erythema, induration/swelling at injection site) and symptoms (e.g., pain, pruritus at injection site). Injection site reactions were graded per NCI CTCAE v4.0. Grade 1=Tenderness with or without associated symptoms (e.g., warmth, erythema, itching); Grade 2=Pain; lipodystrophy; edema; phlebitis; Grade 3=Ulceration or necrosis; severe tissue damage; operative intervention indicated; Grade 4=life-threatening consequences or urgent intervention indicated; Grade=5 death related to AE.
Part 1: Number of Participants With Adverse Events Leading to Etrolizumab Discontinuation From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years) An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. Number of participants who discontinued etrolizumab treatment during the OLE period have been reported here.
Part 1: Number of Participants With Malignancies From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years) An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and regardless of causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. Number of participants who developed malignancies during the OLE period have been reported here.
Part 1: Incidence Rate of Malignancies From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years) Malignancy rate (per 100 participant years) = \[Total number of malignancies (in OLE only) / Total number of participant years at risk (in OLE only)\]\*100. Total participant-years at risk is the sum over all participants of the time intervals (in years) from the first dose of study treatment in Part 1 (OLE) until the participant completes/withdraws from the study (including the 12-week safety follow-up, if applicable).
Part 1: Number of Participants With Hypersensitivity Reactions and Severity of Hypersensitivity Assessed Using NCI-CTCAE v4.0 From Day 1 up to end of 12-week safety follow up in OLE (approximately 6.3 years) Hypersensitivity was reported using the MedDRA anaphylactic reaction standard MedDRA query (SMQ) and Sampson's criteria. Hypersensitivity was assessed as per NCI CTCAE v4.0. Grade 1 = Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated; Grade 2 = Moderate; minimal, local or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3 = Severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living.
Part 2: Number of Participants With Confirmed or Suspected Progressive Multifocal Leukoencephalopathy (PML) From end of safety follow-up in Part 1 or study GA29144 up to maximum of 92 weeks PML was assessed by the PML Subjective Checklist (symptom assessment) and the PML Objective Checklist (neurologic evaluation).
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (287)
Semmelweis Egyetem; Belgyogyaszati es Hematologiai Klinika
🇭🇺Budapest, Hungary
Valley Gastroenterology Consultants
🇺🇸Arcadia, California, United States
University of California San Diego Medical Center
🇺🇸La Jolla, California, United States
VA Long Beach Healthcare System
🇺🇸Long Beach, California, United States
Digestive Care Associates, A Medical Corporation
🇺🇸San Carlos, California, United States
SDG Clinical Research
🇺🇸San Diego, California, United States
Uni. of California at San Francisco; Dept Pediatric, Div. of Gastroenterology, Hepatology & Nutri
🇺🇸San Francisco, California, United States
Peak Gastroenterology Associates
🇺🇸Colorado Springs, Colorado, United States
Innovative Medical Research of South Florida
🇺🇸Aventura, Florida, United States
West Central Gastroenterology d/b/a Gastro Florida
🇺🇸Clearwater, Florida, United States
Scroll for more (277 remaining)Semmelweis Egyetem; Belgyogyaszati es Hematologiai Klinika🇭🇺Budapest, Hungary