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

• Register: ClinicalTrials.gov
• Last refreshed on: 5 June 2023
• Main ID: NCT03478956
• Date of registration: 26/03/2018
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: 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 FENNEL
• Scientific 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
• Date of first enrolment: March 27, 2018
• Target sample size: 24
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT03478956
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Belgium, Germany, Poland, Spain, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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

Exclusion Criteria Related to Inflammatory Bowel Disease:

- 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

Exclusion Criteria Related to Ulcerative Colitis:

- Severe extensive colitis per investigator judgment that colectomy is imminent

Exclusion Criteria Related to Crohn's Disease:

- 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

Exclusion Criteria Related to Prior or Concomitant Therapy:

- 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)



Age minimum: 4 Years
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Crohn's Disease

Ulcerative Colitis

Intervention(s)

Drug: Etrolizumab

Primary Outcome(s)

Area Under the Concentration-Time Curve Within the Last Dosing Interval (AUC-tau) of Etrolizumab During the Randomized Treatment Phase [Time Frame: Predose (dosing days only) on Days 1, 4, 28, 56, (and Days 60 and 70 for Q8W arm only), 84, 88, 98, 112, 126, 140, and 168]

Serum Trough Concentration (Ctrough) of Etrolizumab at the End of Each Dosing Interval During the Randomized Treatment Phase [Time Frame: Predose on Days 28 (Q4W arm only), 56, and 84 (Q4W arm only), and Day 112]

Time to Maximum Serum Concentration (Tmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase [Time Frame: Predose (dosing days only) on Days 1, 4, 28, 56, (and Days 60 and 70 for Q8W arm only), 84, 88, 98, 112, 126, 140, and 168]

Elimination Half-Life (t1/2) of Etrolizumab After Last Dose During the Randomized Treatment Phase [Time Frame: Predose (dosing days only) on Days 1, 4, 28, 56, (and Days 60 and 70 for Q8W arm only), 84, 88, 98, 112, 126, 140, and 168]

Maximum Serum Concentration (Cmax) of Etrolizumab After First and Last Dose During the Randomized Treatment Phase [Time Frame: Predose (dosing days only) on Days 1, 4, 28, 56, (and Days 60 and 70 for Q8W arm only), 84, 88, 98, 112, 126, 140, and 168]

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)]

Secondary Outcome(s)

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)]

Long-Term Safety of Etrolizumab: Number of Participants With Adverse Events by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0 [Time Frame: From Baseline until study discontinuation (up to 8.5 years)]

Number of Participants With Serious Infection-Related Adverse Events by Highest Severity Grade, Assessed According to 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)]

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 6.5 years]

Number of Participants With Confirmed Progressive Multifocal Leukoencephalopathy (PML) During the Post-Treatment PML Monitoring Phase [Time Frame: Approximately every 6 months from last dose of study drug until the end of the PML monitoring phase (up to 104 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)]

Number of Participants With Hypersensitivity Reactions by Highest Severity Grade, Assessed According to 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 Malignancies by Highest Severity Grade, Assessed According to 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)]

Long-Term Safety of Etrolizumab: Number of Participants With Hypersensitivity Reactions by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0 [Time Frame: From Baseline until study discontinuation (up to 8.5 years)]

Long-Term Safety of Etrolizumab: Number of Participants With Serious Infection-Related Adverse Events by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0 [Time Frame: From Baseline until study discontinuation (up to 8.5 years)]

Long-Term Safety of Etrolizumab: Number of Participants With Malignancies by Highest Severity Grade, Assessed According to NCI-CTCAE v4.0 [Time Frame: From Baseline until study discontinuation (up to 8.5 years)]

Secondary ID(s)

CA40192

2017-003649-10

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 05/08/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03478956