Ulcerative ColitisPhase 1FENNELNCT03478956
A Phase I Study of Etrolizumab Followed by Open-Label Extension and Safety Monitoring in Pediatric Patients With Moderate to Severe Ulcerative Colitis or Moderate to Severe Crohn's Disease
A Phase 1 study testing Etrolizumab in people with Ulcerative Colitis and Crohn's Disease, run by Hoffmann-La Roche at 5 sites in 4 countries.
Trial summary
This study will evaluate pharmacokinetics, pharmacodynamics and safety of etrolizumab in pediatric patients of 4 to <18 years of age with moderate to severe ulcerative colitis (UC) or with moderate to severe Crohn's disease (CD). Read more about this study
- Who is it for?
- Ages 4 to 17 years
- Conditions the study is for
- Ulcerative Colitis, Crohn's Disease
- What is being tested?
- Etrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 5 sitesin 4 countries
- Study dates
- 27 Mar 2018to 27 Sep 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age of 4 years to <18 years at the time of signing the Informed Consent Form.
- Weight of 13 kilograms (kg) or more
- Diagnosis of ulcerative colitis (UC) or Crohn's Disease (CD) confirmed by biopsy and established for ≥3 months (i.e., after first diagnosis by a physician according to American College of Gastroenterology [ACG] guidelines) prior to screening
- Inadequate response, loss of response or intolerance to prior immunosuppressants and/or corticosteroid treatment and/or anti-tumor necrosis factor (TNF) therapy
- For postpubertal females of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods during the treatment period and for at least 24 weeks after the last dose of etrolizumab.
- For male patients: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm
Who cannot join
- Pregnant or lactating
- Lack of peripheral venous access
- Congenital or acquired immune deficiency
- Neurological conditions or diseases that may interfere with monitoring for progressive multifocal leukoencephalopathy (PML)
- History of demyelinating disease
- History of cancer, including hematologic malignancy, solid tumors, and carcinoma in situ, within 5 years before screening
Show all 30Show fewer
- Prior extensive colonic resection, subtotal or total colectomy, or planned surgery
- Past or present ileostomy or colostomy
- Diagnosis of indeterminate colitis
- Suspicion of ischemic colitis, radiation colitis, or microscopic colitis
- Diagnosis of toxic megacolon within 12 months of initial screening visit
- Abdominal abscess
- A history or current evidence of colonic mucosal dysplasia
- Patients with fixed symptomatic stenosis of the intestine
- Patients with history or evidence of adenomatous colonic polyps that have not been removed
- Severe extensive colitis per investigator judgment that colectomy is imminent
- Sinus tract with evidence for infection (e.g., purulent discharge) in the clinical judgment of the investigator
- Short-bowel syndrome
- Evidence of abdominal or perianal abscess
- Expected to require surgery to manage CD-related complications during the study
- Any prior treatment with anti-integrin agents (including natalizumab, vedolizumab, and efalizumab), ustekinumab, anti-adhesion molecules (e.g., anti-MAdCAM-1), or rituximab
- Use of IV steroids within 30 days prior to screening with the exception of a single administration of IV steroid
- Use of agents that deplete B or T cells (e.g., alemtuzumab or visilizumab) within 12 months prior to Day 1, with the exception of AZA and 6-MP
- Use of cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil (MMF) within 4 weeks prior to Day 1
- Use of other biologics (e.g. anti-TNF) within 8 weeks before dosing (unless drug level is below detectability before completion of the 8-week interval)
- Chronic nonsteroidal anti-inflammatory drug (NSAID) use
- Patients who are currently using anticoagulants
- Apheresis (i.e., Adacolumn apheresis) within 2 weeks prior to Day 1
- Received any investigational treatment including investigational vaccines within 12 weeks prior to Day 1 of the study or 5 half-lives of the investigational product, whichever is greater
- History of moderate or severe allergic or anaphylactic/anaphylactoid reactions to chimeric, human, or humanized antibodies, fusion proteins, or murine proteins or hypersensitivity to etrolizumab (active drug substance) or any of the excipients (L-histidine, L-arginine, succinic acid, polysorbate 20)
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
Poland2 sites
Gabinet Lekarski, Bartosz Korczowski
Rzeszów, 35-302
Centrum Zdrowia MDM
Warsaw, 00-189
Spain1 site
Hospital Niño Jesus; Servicio de Pediatria - Gastrenterologia y Nutricion
Madrid, 28009
United Kingdom1 site
Royal Manchester Childrens Hospital
Manchester, M13 9WL
About this study
Official title: A Phase I, Open-Label, Randomized, Pharmacokinetic, Pharmacodynamic, and Safety Study of Etrolizumab Followed by Open-Label Extension and Safety Monitoring in Pediatric Patients From 4 Years to Less Than 18 Years Of Age With Moderate to Severe Ulcerative Colitis or Moderate To Severe Crohn's Disease
This study will evaluate pharmacokinetics, pharmacodynamics and safety of etrolizumab in pediatric patients of 4 to <18 years of age with moderate to severe ulcerative colitis (UC) or with moderate to severe Crohn's disease (CD).
- Conditions
- Ulcerative Colitis, Crohn's Disease
- Being tested
- Etrolizumab
- Medical subject headings
- Colitis, Ulcerative, Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtrolizumabDrug
Also called RG7413, RO5490261, PRO145223, rhuMAb Beta7
Etrolizumab was administered by subcutaneous (SC) injection as described for each treatment arm.
| Study group | Role | What they receive |
|---|---|---|
| Etrolizumab Q4W | Experimental | Etrolizumab 1.5 milligrams per kilogram of body weight (mg/kg) was administered by subcutaneous (SC) injection once every 4 weeks (Q4W) for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment period plus 8-week safety follow-up). Participants were then given the option to participate in the 312-week open-label extension (OLE) treatment phase with etrolizumab 1.5 mg/kg SC Q4W followed by the 104-week safety surveillance phase (no etrolizumab treatment) to monitor for progressive multifocal leukoencephalopathy (PML). All participants who chose not to enter the OLE phase after the 24-week randomized treatment phase entered the 104-week PML monitoring phase. Receives: Drug: Etrolizumab |
| Etrolizumab Q8W | Experimental | Etrolizumab 3.0 mg/kg was administered by subcutaneous (SC) injection once every 8 weeks (Q8W) for a total of 2 doses over the course of the 24-week randomized treatment phase (16-week treatment period plus 8-week safety follow-up). Participants were then given the option to participate in the 312-week open-label extension (OLE) treatment phase with etrolizumab 1.5 mg/kg SC Q4W followed by the 104-week safety surveillance phase (no etrolizumab treatment) to monitor for progressive multifocal leukoencephalopathy (PML). All participants who chose not to enter the OLE phase after the 24-week randomized treatment phase entered the 104-week PML monitoring phase. Receives: Drug: Etrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Serum Concentration (Cmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase
Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.
Measured: Arm Etro Q4W: Day 1, 84 and Arm Etro Q8W: Day 1, 56
Time to Maximum Serum Concentration (Tmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase
Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.
Measured: Arm Etro Q4W: Days 1, 84 and Arm Etro Q8W: Days 1, 56
Area Under the Concentration-Time Curve Within the Last Dosing Interval (AUC-tau) of Etrolizumab During the Randomized Treatment Phase
Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.
Measured: Arm Etro Q4W: Days 56, 84, 88, 98, 112 and Arm Etro Q8W: Day 56, 60, 70, 84, 88, 98, 112
Elimination Half-Life (t1/2) of Etrolizumab After Last Dose During the Randomized Treatment Phase
Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.
Measured: Arm Etro Q4W: Days 84, 88, 98, 112, 126, 140, 168 and Arm Etro Q8W: Days 56, 60, 70, 84, 88, 98, 112, 126, 140, 168
Serum Trough Concentration (Ctrough) of Etrolizumab at the End of Each Dosing Interval During the Randomized Treatment Phase
Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method.
Measured: Arm Etro Q4W: Predose on Days 28, 56, 84, 112 and Arm Etro Q8W: Predose on Days 56, 112
Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase
Target engagement of etrolizumab was assessed via measurement of Beta7 receptor occupancy on Beta7 receptor-expressing gut homing lymphocyte subsets in peripheral blood, including CD3, CD4, and CD8 T cells and CD19 B cells, using qualified flow cytometry methods. A decrease to 0% of baseline (BL) in median absolute cell counts of Beta7 receptor-expressing T and B cell subsets with unoccupied Beta7 receptors following etrolizumab treatment indicated maximal receptor occupancy by etrolizumab.
Measured: Predose (dosing days only) at Baseline (Day 1) and on Days 4, 56, 84, 98, and 112 (Treatment Period), and Days 126, 140, and 168 (Follow-Up Period)
Secondary outcomes (11)
Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0), During the Randomized Treatment Phase
All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: 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 or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
Measured: From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks)
Number of Participants With Serious Infection-Related Adverse Events During the Randomized Treatment Phase
Serious infection-related AEs were assessed using NCI-CTCAE v4.0.
Measured: From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks)
Number of Participants With Hypersensitivity Reactions During the Randomized Treatment Phase
Hypersensitivity reactions were assessed using NCI-CTCAE v4.0.
Measured: From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks)
Number of Participants With Malignancies During the Randomized Treatment Phase
Malignancies were assessed using NCI-CTCAE v4.0.
Measured: From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks)
Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline During the Randomized Treatment Phase
Participants were considered to be etrolizumab anti-drug antibody (ADA) positive if they were ADA negative or had missing data at Baseline (BL) but developed an ADA response following study drug exposure (i.e., treatment-induced ADA positive), or if they were ADA positive at baseline and the titer of one or more postbaseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (i.e., treatment-enhanced ADA positive); these ADA positive responses are summarized together (induced + enhanced) in the 'treatment-emergent ADA positive' category. Participants were considered to be ADA negative if they were ADA negative or had missing data at Baseline (BL) and all postbaseline samples were negative (i.e., treatment-emergent ADA negative).
Measured: Predose (dosing days only) on Days 1, 28, 84, 112, and 168 (up to the end of the randomized treatment phase at Week 24)
Long-Term Safety of Etrolizumab: Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0
All adverse events (AEs) were graded for severity using the NCI-CTCAE v4.0. Any AE not specifically listed was assessed per the following 5 grades: 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 or urgent intervention indicated. Grade 5 = death related to AE. Not all grades are appropriate for all AEs; some AEs have fewer than 5 options. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade.
Measured: OLE Period: From end of Week 24 to end of 12-week safety follow-up (up to 195 weeks); PML Period: After completion of safety follow up in Randomized Treatment phase or after completion of safety follow up after OLE treatment, up to approximately 92 weeks
Long-Term Safety of Etrolizumab: Number of Participants With Serious Infection-Related Adverse Events
Serious infection-related AEs were assessed using NCI-CTCAE v4.0.
Measured: OLE Period: From end of Week 24 to end of 12-week safety follow-up (up to 195 weeks); PML Period: After completion of safety follow up in Randomized Treatment phase or after completion of safety follow up after OLE treatment, up to approximately 92 weeks
Long-Term Safety of Etrolizumab: Number of Participants With Hypersensitivity Reactions
Hypersensitivity reactions were assessed using NCI-CTCAE v4.0.
Measured: OLE Period: From end of Week 24 to end of 12-week safety follow-up (up to 195 weeks); PML Period: After completion of safety follow up in Randomized Treatment phase or after completion of safety follow up after OLE treatment, up to approximately 92 weeks
Long-Term Safety of Etrolizumab: Number of Participants With Malignancies
Malignancies were assessed using NCI-CTCAE v4.0.
Measured: OLE Period: From end of Week 24 to end of 12-week safety follow-up (up to 195 weeks); PML Period: After completion of safety follow up in Randomized Treatment phase or after completion of safety follow up after OLE treatment, up to approximately 92 weeks
Long-Term Safety of Etrolizumab: Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline
Participants were considered to be etrolizumab anti-drug antibody (ADA) positive if they were ADA negative or had missing data at Baseline (BL) but developed an ADA response following study drug exposure (i.e., treatment-induced ADA positive), or if they were ADA positive at baseline and the titer of one or more postbaseline samples was at least 0.60 titer unit greater than the titer of the baseline sample (i.e., treatment-enhanced ADA positive); these ADA positive responses are summarized together (induced + enhanced) in the 'treatment-emergent ADA positive' category. Participants were considered to be ADA negative if they were ADA negative or had missing data at Baseline (BL) and all postbaseline samples were negative (i.e., treatment-emergent ADA negative).
Measured: Predose (dosing days only) at Baseline (Day 1), Days 28, 84, and 112, Weeks 24, 36, 72, and 120, and every 12 weeks thereafter for up to 4.25 years
Number of Participants With Confirmed Progressive Multifocal Leukoencephalopathy (PML) During the Post-Treatment PML Monitoring Phase
The safety surveillance PML-monitoring phase (no etrolizumab treatment) consisted of telephone calls approximately every 6 months with administration of the protocol's PML Subjective Checklist. If there were any signs or symptoms suggestive of PML identified on this subjective checklist during the telephone call, the participant was asked to come into the clinic for a neurologic examination. The protocol's PML Algorithm was followed for any suspected case of PML, and any confirmed case of PML would be reported as a serious adverse event.
Measured: PML Period: After completion of safety follow up in Randomized Treatment period or after completion of safety follow up after OLE treatment, up to approximately 92 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2018
- Study start27 Mar 2018
- Primary completion2 Dec 2019
- Study completion27 Sep 2023
Why it stopped: The study was terminated due to program discontinuation, based on mixed efficacy results in the adult ulcerative colitis and Crohn's disease studies. There were no safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03478956
- Sponsor's protocol ID
- CA40192
- Other IDs
- 2017-003649-10, 2017
- Acronym
- FENNEL
- Status last verified
- Nov 2024
- First submitted
- 26 Mar 2018
- Last updated
- 27 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-Label, Randomized, Pharmacokinetic, Pharmacodynamic, and Safety Study of Etrolizumab Followed by Open-Label Extension and Safety Monitoring in Pediatric Patients From 4 Years to Less Than 18 Years Of Age With Moderate to Severe Ulcerative Colitis or Moderate To Severe Crohn's Disease
- ClinicalTrials.gov ID
- NCT03478956
- Acronym / sponsor ID
- FENNEL / CA40192
- Conditions
- Ulcerative Colitis, Crohn's Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated due to program discontinuation, based on mixed efficacy results in the adult ulcerative colitis and Crohn's disease studies. There were no safety concerns.
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 27 Mar 2018 (actual)
- Primary completion
- 2 Dec 2019 (actual)
- Study completion
- 27 Sep 2023 (actual)
- First posted
- 27 Mar 2018 (actual)
- Results
- Posted 5 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate pharmacokinetics, pharmacodynamics and safety of etrolizumab in pediatric patients of 4 to <18 years of age with moderate to severe ulcerative colitis (UC) or with moderate to severe Crohn's disease (CD).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Etrolizumab Q4W | Experimental | Drug: EtrolizumabEtrolizumab 1.5 milligrams per kilogram of body weight (mg/kg) was administered by subcutaneous (SC) injection once every 4 weeks (Q4W) for a total of 4 doses over the course of the 24-week randomized treatment phase (16-week treatment period plus 8-week safety follow-up). Participants were then given the option to participate in the 312-week open-label extension (OLE) treatment phase with etrolizumab 1.5 mg/kg SC Q4W followed by the 104-week safety surveillance phase (no etrolizumab treatment) to monitor for progressive multifocal leukoencephalopathy (PML). All participants who chose not to enter the OLE phase after the 24-week randomized treatment phase entered the 104-week PML monitoring phase. |
| Etrolizumab Q8W | Experimental | Drug: EtrolizumabEtrolizumab 3.0 mg/kg was administered by subcutaneous (SC) injection once every 8 weeks (Q8W) for a total of 2 doses over the course of the 24-week randomized treatment phase (16-week treatment period plus 8-week safety follow-up). Participants were then given the option to participate in the 312-week open-label extension (OLE) treatment phase with etrolizumab 1.5 mg/kg SC Q4W followed by the 104-week safety surveillance phase (no etrolizumab treatment) to monitor for progressive multifocal leukoencephalopathy (PML). All participants who chose not to enter the OLE phase after the 24-week randomized treatment phase entered the 104-week PML monitoring phase. |
Who may qualify
- Ages
- 4 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Age of 4 years to <18 years at the time of signing the Informed Consent Form.
- Weight of 13 kilograms (kg) or more
- Diagnosis of ulcerative colitis (UC) or Crohn's Disease (CD) confirmed by biopsy and established for ≥3 months (i.e., after first diagnosis by a physician according to American College of Gastroenterology [ACG] guidelines) prior to screening
- Inadequate response, loss of response or intolerance to prior immunosuppressants and/or corticosteroid treatment and/or anti-tumor necrosis factor (TNF) therapy
- For postpubertal females of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use acceptable contraceptive methods during the treatment period and for at least 24 weeks after the last dose of etrolizumab.
Key exclusion criteria (30 listed)
- Pregnant or lactating
- Lack of peripheral venous access
- Congenital or acquired immune deficiency
- Neurological conditions or diseases that may interfere with monitoring for progressive multifocal leukoencephalopathy (PML)
- History of demyelinating disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EtrolizumabAlso: RG7413, RO5490261, PRO145223, rhuMAb Beta7Etrolizumab was administered by subcutaneous (SC) injection as described for each treatment arm. | Drug | Etrolizumab Q4W, Etrolizumab Q8W |
Primary outcome
Maximum Serum Concentration (Cmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase
Time frame: Arm Etro Q4W: Day 1, 84 and Arm Etro Q8W: Day 1, 56
Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.
Time to Maximum Serum Concentration (Tmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase
Time frame: Arm Etro Q4W: Days 1, 84 and Arm Etro Q8W: Days 1, 56
Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.
Area Under the Concentration-Time Curve Within the Last Dosing Interval (AUC-tau) of Etrolizumab During the Randomized Treatment Phase
Time frame: Arm Etro Q4W: Days 56, 84, 88, 98, 112 and Arm Etro Q8W: Day 56, 60, 70, 84, 88, 98, 112
Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.
Elimination Half-Life (t1/2) of Etrolizumab After Last Dose During the Randomized Treatment Phase
Time frame: Arm Etro Q4W: Days 84, 88, 98, 112, 126, 140, 168 and Arm Etro Q8W: Days 56, 60, 70, 84, 88, 98, 112, 126, 140, 168
Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method. Non-compartmental analysis methods were employed to calculate PK parameters.
Serum Trough Concentration (Ctrough) of Etrolizumab at the End of Each Dosing Interval During the Randomized Treatment Phase
Time frame: Arm Etro Q4W: Predose on Days 28, 56, 84, 112 and Arm Etro Q8W: Predose on Days 56, 112
Etrolizumab concentrations in all pharmacokinetics (PK) samples were measured using a validated assay method.
Percentage of Baseline Absolute Numbers of Beta7 Receptor-Expressing Gut Homing CD3, CD4, and CD8 T Cells and CD19 B Cells With Unoccupied Beta7 Receptors in Peripheral Blood, Assessed by Flow Cytometry, During the Randomized Treatment Phase
Time frame: Predose (dosing days only) at Baseline (Day 1) and on Days 4, 56, 84, 98, and 112 (Treatment Period), and Days 126, 140, and 168 (Follow-Up Period)
Target engagement of etrolizumab was assessed via measurement of Beta7 receptor occupancy on Beta7 receptor-expressing gut homing lymphocyte subsets in peripheral blood, including CD3, CD4, and CD8 T cells and CD19 B cells, using qualified flow cytometry methods. A decrease to 0% of baseline (BL) in median absolute cell counts of Beta7 receptor-expressing T and B cell subsets with unoccupied Beta7 receptors following etrolizumab treatment indicated maximal receptor occupancy by etrolizumab.
11 secondary outcomes
Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0), During the Randomized Treatment Phase
Time frame: From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks)
Number of Participants With Serious Infection-Related Adverse Events During the Randomized Treatment Phase
Time frame: From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks)
Number of Participants With Hypersensitivity Reactions During the Randomized Treatment Phase
Time frame: From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks)
Number of Participants With Malignancies During the Randomized Treatment Phase
Time frame: From Baseline until 12 weeks (Q4W arm only) or 16 weeks (Q8W arm only) after the last dose of study drug during the randomized treatment phase (up to 24 weeks)
Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline During the Randomized Treatment Phase
Time frame: Predose (dosing days only) on Days 1, 28, 84, 112, and 168 (up to the end of the randomized treatment phase at Week 24)
Long-Term Safety of Etrolizumab: Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0
Time frame: OLE Period: From end of Week 24 to end of 12-week safety follow-up (up to 195 weeks); PML Period: After completion of safety follow up in Randomized Treatment phase or after completion of safety follow up after OLE treatment, up to approximately 92 weeks
Long-Term Safety of Etrolizumab: Number of Participants With Serious Infection-Related Adverse Events
Time frame: OLE Period: From end of Week 24 to end of 12-week safety follow-up (up to 195 weeks); PML Period: After completion of safety follow up in Randomized Treatment phase or after completion of safety follow up after OLE treatment, up to approximately 92 weeks
Long-Term Safety of Etrolizumab: Number of Participants With Hypersensitivity Reactions
Time frame: OLE Period: From end of Week 24 to end of 12-week safety follow-up (up to 195 weeks); PML Period: After completion of safety follow up in Randomized Treatment phase or after completion of safety follow up after OLE treatment, up to approximately 92 weeks
Long-Term Safety of Etrolizumab: Number of Participants With Malignancies
Time frame: OLE Period: From end of Week 24 to end of 12-week safety follow-up (up to 195 weeks); PML Period: After completion of safety follow up in Randomized Treatment phase or after completion of safety follow up after OLE treatment, up to approximately 92 weeks
Long-Term Safety of Etrolizumab: Number of Participants With Anti-Drug Antibodies (ADAs) to Etrolizumab at Baseline and Post-Baseline
Time frame: Predose (dosing days only) at Baseline (Day 1), Days 28, 84, and 112, Weeks 24, 36, 72, and 120, and every 12 weeks thereafter for up to 4.25 years
Number of Participants With Confirmed Progressive Multifocal Leukoencephalopathy (PML) During the Post-Treatment PML Monitoring Phase
Time frame: PML Period: After completion of safety follow up in Randomized Treatment period or after completion of safety follow up after OLE treatment, up to approximately 92 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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IBD, Ulcerative Colitis
RecruitingObservational study
Characterization of Colorectal Dysplasic Lesions and Stratification of Their Evolving Risk in Inflammatory Bowel Disease Patients: a Prospective, Observational and Multicenter Study
Crohn Disease (CD), Colitis Ulcerative
Enrolling by invitationPhase 4
MOdel-Informed Precision Dosing of Ustekinumab and VEdolizumab in Inflammatory Bowel Disease
Inflammatory Bowel Diseases, Crohn Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
5 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Etrolizumab in people with Ulcerative Colitis and Crohn's Disease, run by Hoffmann-La Roche at 5 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Poland, Belgium, Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Serum Concentration (Cmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase (time frame: Arm Etro Q4W: Day 1, 84 and Arm Etro Q8W: Day 1, 56). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2024.