A Phase 3, Multi-Center Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Risankizumab with Open-Label Induction, Randomized Double-Blind Maintenance, and Long-Term Extension Periods in Pediatric Subjects (2 to < 18 Years of Age) with Moderately to Severely Active Crohn's Disease
- Trial ID
- 2022-502050-14-00
- Protocol
- M16-194
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **pharmacokinetics**, efficacy, and safety of **risankizumab** in pediatric subjects aged 2 to less than 18 years with moderately to severely active **Crohn's disease**. This population includes those who have shown intolerance or inadequate response to aminosalicylates, oral locally acting corticosteroids, systemic corticosteroids, immunomodulators (IMMs), and/or biologic therapies. Understanding the pharmacokinetics and safety profile of risankizumab in this demographic is crucial for optimizing treatment strategies and improving clinical outcomes in pediatric patients with Crohn's disease.
Participants
The clinical trial involves a total of **76 participants** diagnosed with **Crohn's disease**, focusing on pediatric subjects aged 2 to less than 18 years. The study population includes both male and female participants who have demonstrated intolerance or inadequate response to aminosalicylates, oral locally acting corticosteroids, systemic corticosteroids, immunomodulators (IMMs), and/or biologic therapies. Participants are required to be in good general health, as determined by medical history, physical examination, laboratory profile, and a 12-lead ECG. The trial population was selected based on specific criteria, including a confirmed diagnosis of Crohn's disease at least three months prior to baseline and evidence of moderately to severely active disease. Lifestyle considerations such as diet and physical activity are not specified. The study includes vulnerable populations, and participants must comply with the study protocol, including the use of birth control for females of childbearing potential. The trial aims to assess the pharmacokinetics, efficacy, and safety of risankizumab in this demographic.
Plans and Procedures
The clinical trial is designed to evaluate the **pharmacokinetics**, efficacy, and safety of **risankizumab** in pediatric subjects aged 2 to less than 18 years with moderately to severely active **Crohn's disease**. This is a Phase 3, multi-center study with an open-label induction phase, followed by a randomized, double-blind maintenance phase, and a long-term extension period. The trial is expected to last until July 2033, with recruitment starting in February 2024. Participants will be involved for a maximum treatment period of 52 weeks, depending on their cohort assignment.
The trial includes several study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as weight, laboratory values, and a confirmed diagnosis of Crohn's disease. Participants must have demonstrated intolerance or inadequate response to specific therapies. The screening visit will also include a medical history review, physical examination, and laboratory tests. Following the screening, eligible participants will enter the induction phase, where they will receive **risankizumab** via subcutaneous injection or intravenous infusion, depending on the cohort. The maintenance phase will involve randomization to either continue with **risankizumab** or receive a placebo, maintaining the double-blind nature of the study.
Follow-up visits will occur at regular intervals to monitor the participants' response to treatment, assess safety, and collect data on primary and secondary endpoints, such as clinical remission and endoscopic response. The end-of-study visit will conclude the trial for each participant, involving a final assessment of their health status and any long-term effects of the treatment. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with the study protocol, or if the investigator deems it necessary for their safety.
Treatment
The clinical trial involves the administration of **Risankizumab**, a biologic agent classified as a protein of other origin. The pharmaceutical form of Risankizumab is a solution for injection in a pre-filled syringe. It is administered via **subcutaneous injection**. The maximum daily dose is 360 mg, with a total maximum dose of 2520 mg over a treatment period of up to 52 weeks. The product is identified by the sponsor product code ABBV-066 and is manufactured by AbbVie, Inc. and AbbVie Deutschland GmbH & Co. KG.
Another formulation of Risankizumab, identified as ABBV-066 / Risankizumab, is provided as a solution for infusion. This formulation is administered through **intravenous infusion**. The maximum daily dose for this formulation is 600 mg, with a total maximum dose of 1800 mg over a treatment period of up to 8 weeks. This product is also manufactured by AbbVie Deutschland GmbH & Co. KG.
The study includes the use of a **placebo** as a comparator treatment. The placebo is designed to match the 180 mg and 90 mg solutions for injection. These placebo formulations do not contain any active substance and are used to maintain the double-blind nature of the trial. The placebo is administered in a manner consistent with the active treatment to ensure blinding is maintained throughout the study.
Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. The trial aims to evaluate the pharmacokinetics, efficacy, and safety of Risankizumab in pediatric subjects with moderately to severely active Crohn's Disease who have shown intolerance or inadequate response to other therapies.
Efficacy
The efficacy of **risankizumab** in the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoints for Cohort 3 include the achievement of clinical remission per the Pediatric Crohn's Disease Activity Index (PCDAI) at Week 64 and the achievement of endoscopic response at the same time point. Secondary endpoints for Cohort 3 include the achievement of clinical remission per PCDAI at Week 12, endoscopic response at Week 12, endoscopic remission at Week 12, endoscopic remission at Week 64, and corticosteroid-free clinical remission per PCDAI at Week 64.
For PK Leading Cohort 1 and Cohort 2, the primary endpoints include pharmacokinetic parameters such as Cmax, Tmax, and AUCtau of **risankizumab**. Secondary endpoints for these cohorts also include the achievement of clinical remission and endoscopic response at Weeks 12 and 64, as well as endoscopic remission and corticosteroid-free clinical remission at these time points. The efficacy assessments will be conducted at specified time points, including Week 12 and Week 64, using validated scales such as the PCDAI and endoscopic evaluations. These assessments will provide comprehensive data on the efficacy of **risankizumab** in pediatric subjects with moderately to severely active Crohn's disease.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Subjects and/or their legally authorized representative must voluntarily sign and date an informed consent (and assent for minors as required by applicable regulation), approved by an IEC/IRB, prior to the initiation of any screening or study-specific procedures. In Japan, a subject's parent or legal guardian must be willing to give written informed consent. In China, the legal guardian must be willing to give written informed consent; subjects aged 8 to < 18 years must also be willing to give written informed consent.
- Must have endoscopic evidence of mucosal inflammation as documented by the SES-CD of ≥ 6 for ileocolonic or colonic disease (or SES-CD of ≥ 4 for isolated ileal disease). All eligible scores exclude the presence of narrowing component and are confirmed by a central reader.
- Demonstrated intolerance or IR to one or more of the following categories of drugs: aminosalicylates (this drug class is not sufficient for eligibiliy for subjects in FR, IT, NL, ES and SE), oral locally acting corticosteroids, systemic steroids (prednisone or equivalent), IMMs, and/or biologic therapies.
- Subject is judged to be in good general health, as determined by the investigator based upon the results of a medical history, physical examination, laboratory profile, and a 12-lead ECG performed during the Screening period.
- Subjects with CD involving the colon of > 9 years' duration must have documented evidence of a negative surveillance colonoscopy for dysplasia within 24 months before Baseline.
- Females of child-bearing potential must have a negative serum pregnancy test at the Screening visit and a negative urine pregnancy test at Baseline prior to the first dose of study drug. • Subjects with a borderline serum pregnancy test at Screening must have absence of clinical suspicion of pregnancy or other pathological causes of borderline results and a serum pregnancy test ≥3 days later to document continued lack of a positive result (unless prohibited by local requirements). • Urine pregnancy test: Subjects with a urine pregnancy test at Baseline that is borderline or ambiguous must have a serum pregnancy test. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
- Female subjects of childbearing potential must practice at least 1 protocol-specified method of birth control, from Baseline through at least 147 days (21 weeks or as guided by the local risankizumab label [if approved], whichever is longer) after the last dose of study drug (local practices may require 2 methods of birth control; refer to Section 5.2 for more details on change in childbearing potential of female subjects and contraception). Female subjects of nonchildbearing potential do not need to use birth control.
- Are willing and able to comply with procedures required in this protocol.
- Pediatric individuals, 2 to < 18 years old. If a subject turns 18 years old at any point after Baseline, they may continue in the study. • PK Cohort 1 – ages include 6 to < 18 years at the time of Baseline. • PK Cohort 2 – ages include 2 to < 6 years at the time of Baseline. • Expansion Cohort 3 – ages include 2 to < 18 years at the time of Baseline.
- Weight at the time of Screening and Baseline must be ≥ 10 kg.
- Laboratory values meeting the following criteria within the Screening period prior to the first dose of study drug: • Serum ALT ≤ 2 × ULN; • Serum AST ≤ 2 × ULN; • Serum total bilirubin < 2 mg/dL; except for subjects with isolated elevation of indirect bilirubin relating to Gilbert syndrome; • Total WBC count ≥ 3,000/μL; • ANC ≥ 1,500/µL; • Platelet count ≥ 100,000/µL; • Hemoglobin ≥ 8 g/dL (80 g/L).
- Confirmed diagnosis of CD at least 3 months (90 days) prior to Baseline. Appropriate documentation of biopsy results consistent with the diagnosis of CD, in the assessment of the investigator, must be available.
- Must have moderately to severely active CD, as defined by the PCDAI score > 30 assessed at Baseline.
Exclusion Criteria
- Employees of the sponsor and/or study sites and their immediate family members may not be enrolled in this study.
- Subject must not have a history of clinically significant (per investigator's judgement) drug or alcohol abuse within the last 6 months.
- Subject must not have a history of hereditary fructose intolerance (a rare genetic condition) or an allergic reaction or significant sensitivity to constituents of the study drug (and its excipients) and/or other products in the same class.
- Subject must not have had a major surgery performed within 12 weeks prior to Baseline or planned during the conduct of the study (e.g., inguinal hernia repair, cholecystectomy, intestinal resection).
- Subject must not have any of the following medical disorders: (a) Current diagnosis of ulcerative colitis, indeterminate colitis, or monogenic IBD. (b) A diagnosis of CD prior to 2 years of age. (c) A diagnosis or suspected diagnosis of a primary immunodeficiency. (d) Currently known complications of CD such as: • Active abscess (abdominal or perianal); • Symptomatic bowel strictures; • 2 missing segments of the following 5 segments: terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum; • Fulminant colitis; • Toxic megacolon; • Or any other manifestation that might require surgery while enrolled in the study. (e) Ostomy or ileoanal pouch. (f) Diagnosis of short gut or short bowel syndrome. (g) Surgical bowel resection within the past 3 months prior to Baseline (excluding gastrointestinal surgeries which are not bowel resections such as appendectomy or ostomy closure), or a history of >3 bowel resections.
- Subjects must not have evidence of: (a) HBV or HCV infection, defined as: • HBV: HBs Ag positive (+) test or detected sensitivity on the HBV DNA PCR qualitative test for subjects who are HBc Ab positive (+) (and for HBs Ab positive [+] subjects where mandated by local requirements). • HCV: HCV RNA detectable in any subject with anti-HCV Ab. (b) HIV, defined as confirmed positive anti-HIV Ab test. Note: In case a screened subject has a confirmed positive HIV Ab test, eligibility criterion 11 (Subject is judged to be in good general health criteria…) should be selected in eCRF for documentation of screening failure. (c) Active TB. For subjects with latent TB, please see Section 3.13 of the Operations Manual (Appendix J). (d) Active systemic infection/clinically important infection during the last 2 weeks prior to Baseline visit as assessed by the investigator. (e) Any infection with C. difficile or other intestinal pathogen during Screening.
- Subjects must not have any of the following medical diseases or disorders: (a) Recent (within past 6 months) cerebrovascular accident or MI. (b) History of an organ transplant which requires continued immunosuppression. (c) Active or suspected malignancy or history of any malignancy within the last 5 years except for successfully treated NMSC or localized carcinoma in situ of the cervix. (d) Previous history of dysplasia of the gastrointestinal tract or found to have dysplasia, other than completely removed low-grade dysplastic lesions, in any biopsy performed during the Screening endoscopy.
- In subjects who tested positive for COVID-19, at least 5 days have passed since a COVID-19 positive test result in asymptomatic subjects. Subjects with mild/moderate COVID-19 infection can be enrolled if resolution of fever without use of antipyretics for 24 hours and improvement in other symptoms or 5 days since the COVID-19 positive test result (whichever comes last). Subject may be re-screened if judged to be in good general health, as determined by the investigator based upon the medical history and physical examination.
- Subject must not have concurrent clinically significant medical conditions other than the indication being studied or any other reason that the investigator determines would interfere with the subject's participation in this study, would make the subject an unsuitable candidate to receive study drug, or would put the subject at risk by participating in the study.
- Female subjects may not be pregnant, breastfeeding, or considering becoming pregnant during the study or for approximately 147 days (21 weeks or as guided by the local risankizumab label [if approved], whichever is longer) after the last dose of study drug.
- Subject must not have received any replicating live viral or bacterial vaccine within 4 weeks prior to the first dose of study drug or expect the need for live vaccination during study participation including at least 140 days (20 weeks or as guided by the local risankizumab label [if approved], whichever is longer) after the last dose of study drug.
- Subjects are excluded if: (a) Subject on CD-related antibiotics who has not been on stable doses for greater than, or discontinued within, 14 days prior to Baseline. (b) Subject on oral aminosalicylates who has not been on stable doses for greater than, or discontinued within, at least 14 days prior to Baseline. (c) Subject taking oral corticosteroids: • Budesonide > 9 mg/day • Prednisone or equivalent > 20 mg/day, or • Has not been on the current course for ≥ 14 days prior to Baseline and on a stable dose for ≥ 7 days prior to Baseline. (d) Subject on IMMs (AZA, 6-MP, MTX) who: • Has not been on the current course for ≥ 42 days prior to Baseline • Has not been on a stable dose for ≥ 28 days prior to Baseline, or • Has stopped IMM ≤ 28 days prior to Baseline
- For medications and treatments taken during the Screening Period, subjects are excluded if: (a) Subjects on growth hormone who have not been on a stable dose for at least 12 weeks prior to Baseline. Subjects must consent to remain on a stable dose through the duration of the study. (b) Subject who received IV anti-infectives within 28 days prior to Baseline visit or oral/intramuscular anti-infectives (non-CD-related) within 14 days prior to the Baseline visit. This does not apply to TB prophylaxis. (c) Subject who received total parenteral nutrition within 28 days prior to Baseline. (d) If receiving exclusive enteral nutrition, must have been on a stable regimen for at least 2 weeks prior to Baseline. (e) Subject who received oral cyclosporine, oral tacrolimus, mycophenolate mofetil, or thalidomide within 28 days prior to Baseline. (f) Subject who received fecal microbial transplantation within 28 days prior to Baseline.
- The following prior medications and treatments are not allowed: (a) Subject who received any: • Biologic agent: infliximab and/or adalimumab, including biosimilars, within 2 half-lives (3 and 4 weeks, respectively) prior to Baseline. Or • Any investigational biologic or other agent or procedure within 30 days or 5 half-lives prior to Baseline, whichever is longer, or currently enrolled in another interventional clinical study. (b) Subject with prior exposure to p19 inhibitors (e.g., risankizumab and mirikizumab). (c) Subject has been taking combination of oral budesonide and oral prednisone (or equivalent), with the exception of inhalers, within 14 days prior to Screening or during the Screening period. (d) Subject who received IV/intramuscular corticosteroids during the Screening period. (e) Subject who received therapeutic enema or suppository, other than required for endoscopy during the Screening period. (f) Subject who received apheresis (e.g., Adacolumn apheresis) ≤ 60 days prior to Screening or during the Screening period. (g) Subject who has concomitant cannabis use either recreational or for medical reasons within 14 days of Baseline or any history of clinically significant drug or alcohol abuse in the last 6 months.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Recruiting | 01 Feb 2024 | 8 |
 Bulgaria | Recruiting | 01 Feb 2024 | 11 |
 Czechia | Not Recruiting | 01 Feb 2024 | 4 |
 France | Recruiting | 01 Feb 2024 | 7 |
 Germany | Recruiting | 01 Feb 2024 | 4 |
 Italy | Recruiting | 01 Feb 2024 | 6 |
 The Netherlands | Recruiting | 01 Feb 2024 | — |
 Poland | Recruiting | 01 Feb 2024 | 6 |
 Spain | Recruiting | 01 Feb 2024 | 5 |
 Sweden | Recruiting | 01 Feb 2024 | 6 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
ABBV-066 / Risankizumab | Test | SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 00 | 8 | PRD10391031 |
ABBV-066 | Test | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS INJECTION | 00 | 52 | PRD10369455 |
Matching Placebo for 90 mg solution for injection | Placebo | N/A | — | — | — | N/A |
Matching placebo for 180 mg solution for
injection | Placebo | N/A | — | — | — | N/A |
Risankizumab | Test | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS INJECTION | 00 | 52 | PRD9602765 |