Efficacy, Safety and Pharmacokinetics of BI 655066/ABBV-066 (Risankizumab) in Patients With Active, Moderate-to-severe Crohn's Disease.

NCT02031276 | Completed Phase 2 Results DMC

• 3 other identifiers: M15-9932013-002902-291311.6
• Study Type: interventional
• Target: 121
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a proof of concept, multi-center, randomized, double-blind, placebo-controlled, parallel-group phase 2 dose-ranging study of BI 655066/ABBV-066 (risankizumab), an IL-23 p19 antagonist monoclonal antibody, in patients with moderately to severely active Crohn's disease.

Conditions

Crohn Disease

Keywords

ABBV-066; BI 655066; risankizumab

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Clinical Remission at Week 12

  The CDAI is a measure of clinical response and remission. The CDAI includes 8 variables encompassing both patient-reported (symptoms, general well-being) and objective (medication usage, laboratory variables, presence of abdominal mass or complications, and weight) variables. For symptoms scores, patients keep track of daily symptoms on a diary card and the daily symptom scores are summed for the week. Each item in the CDAI is assigned a specific weight, and the weighted values of the items are totaled to produce the CDAI. Higher CDAI scores indicate greater disease activity, with a lower limit of 0 and no set upper limit: \< 150 indicates remission, 150 - 219 indicates mildly active disease, 220 - 450 indicates moderately active disease, and \> 450 indicates severely active disease. CDAI clinical remission is defined as CDAI \< 150 at Week 12. Nonresponder imputation (NRI): missing values were counted as nonresponders.

  Week 12

Secondary Outcomes (5)

• Percentage of Participants Achieving CDAI Clinical Response at Week 12

  Week 12

• Percentage of Participants Achieving Crohn's Disease Endoscopic Index of Severity (CDEIS) Remission at Week 12

  Week 12

• Percentage of Participants Achieving CDEIS Response at Week 12

  Week 12

• Percentage of Participants Achieving Mucosal Healing at Week 12

  Week 12

• Percentage of Participants Achieving Deep Remission at Week 12

  Week 12

Study Arms (3)

Double-blind Placebo IV

PLACEBO COMPARATOR

Participants randomized to receive double-blind placebo for risankizumab by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3.

Drug: risankizumab IV; Drug: risankizumab SC; Drug: Placebo

Double-blind Risankizumab 200 mg IV

EXPERIMENTAL

Participants randomized to receive double-blind risankizumab 200 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3.

Drug: risankizumab IV; Drug: risankizumab SC

Double-blind Risankizumab 600 mg IV

EXPERIMENTAL

Participants randomized to receive double-blind risankizumab 600 mg by intravenous (IV) injection for 12 weeks in Period 1, followed by open-label risankizumab 600 mg IV in Period 2, then open-label risankizumab 180 mg by subcutaneous (SC) injection in Period 3.

Drug: risankizumab IV; Drug: risankizumab SC

Interventions

risankizumab IV DRUG

risankizumab administered by IV infusion

Also known as: BI 655066, ABBV-066

Double-blind Placebo IV; Double-blind Risankizumab 200 mg IV; Double-blind Risankizumab 600 mg IV

risankizumab SC DRUG

risankizumab administered by SC injection

Also known as: BI 655066, ABBV-066

Double-blind Placebo IV; Double-blind Risankizumab 200 mg IV; Double-blind Risankizumab 600 mg IV

Placebo DRUG

Placebo for risankizumab administered by IV infusion

Double-blind Placebo IV

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women 18-75 years at the time of consent.
• Diagnosis of Crohn's disease (CD) at least 3 months prior to screening.
• Moderate to severe active CD, defined as Crohn's Disease Activity Index (CDAI) ≥ 220 and ≤ 450.
• Presence of mucosal ulcers in at least one segment of the ileum or colon and a Crohn's Disease Endoscopic Index of Severity (CDEIS) score ≥ 7 (for patients with isolated ileitis, ≥4), as assessed by ileocolonoscopy and confirmed by central independent reviewer before randomization
• Patients who are naive or experienced to 1 or more TNF antagonists (infliximab, adalimumab, or certolizumab pegol) at a dose approved for CD. TNF antagonist experienced patients may have stopped anti-TNF treatment due to primary or secondary non-responsiveness, intolerance or for other reasons.
• Female patients:
• Women of childbearing potential (not surgically sterilized and between menarche and 1 year postmenopause), that, if sexually active agree to use one of the appropriate medically accepted methods of birth control in addition to the consistent and correct use of a condom from date of screening until 15 weeks after last administration of study medication. Medically accepted methods of contraception are: ethinyl estradiol containing contraceptives, diaphragm with spermicide substance, and intra-uterine-device, or
• Surgically sterilized female patients with documentation of prior hysterectomy, tubal ligation or complete bilateral oophorectomy, or
• Postmenopausal women with postmenopausal is defined as permanent cessation = 1 year of previously occurring menses, and
• Negative serum ß-Human Chorionic Gonadotrophin (ß-HCG) test at screening and urine pregnancy test prior to randomization.
• Male patients:
• Who are documented to be sterile, or
• Who consistently and correctly use effective method of contraception (i.e. condoms) during the study and 15 weeks after last administration of study medication.
• Have the capacity to understand and sign an informed consent form.
• Be able to adhere to the study visit schedule and other protocol requirements.

You may not qualify if:

• Have complications of CD such as strictures, stenoses, short gut syndrome, or any other manifestation that might require surgery, could preclude the use of the CDAI to assess response to therapy, or would possibly confound the evaluation of benefit from treatment with BI 655066.
• Have any current or prior abscesses, unless they have been drained and treated at least 6 weeks prior to randomization and are not anticipated to require surgery. Patients with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses present.
• Have had any kind of bowel resection or diversion within 6 months or any other intra-abdominal surgery within 3 months prior to screening. Patients with a current ileostomy or colostomy are excluded.
• Have received treatment with:
• Total parenteral nutrition (TPN) within 2 weeks of screening.
• Any dose of ustekinumab (Stelara®).
• Anti-TNF therapy ≤ 8 weeks prior to the first administration of study medication or any other biologic ≤ 8 weeks prior to the first administration of study drug or within 5 times the half-life of the biologic prior to the first administration of study agent, whichever is longer.
• Natalizumab, efalizumab, or agents that deplete B or T cells (e.g., rituximab, alemtuzumab, or visilizumab) within 6 months of screening, or, if after receiving these agents, evidence is available at screening of persistent depletion of the targeted lymphocyte population.
• Any investigational drug within the previous 4 weeks or 5 times the half-life of the investigational agent prior to the first administration of study agent, whichever is longer.
• Regular daily use of opioids for medical reasons within previous 3 months prior to the first administration of study agent.
• Rectal 5-aminosalicylic acid (5-ASA) compounds, parenteral or rectal corticosteroids must have been discontinued at least 4 weeks prior to visit 2.
• Cannot adhere to the concomitant medication requirements specified in section 4.2.2.
• Are pregnant, nursing, or planning pregnancy (both men and women) while enrolled in the study, or within 15 weeks after receiving the last dose of study medication.
• Have used apheresis (e.g., Adacolumn apheresis) ≤ 2 weeks prior to screening.
• Have received any live bacterial or viral vaccination ≤ 12 weeks prior to Day 1. Patients must agree not to receive a live virus or bacterial vaccination during the study or up to 12 months after the last administration of study drug.

Sponsors & Collaborators

• AbbVie: lead
• Boehringer Ingelheim: collaborator

Related Publications (2)

• Feagan BG, Panes J, Ferrante M, Kaser A, D'Haens GR, Sandborn WJ, Louis E, Neurath MF, Franchimont D, Dewit O, Seidler U, Kim KJ, Selinger C, Padula SJ, Herichova I, Robinson AM, Wallace K, Zhao J, Minocha M, Othman AA, Soaita A, Visvanathan S, Hall DB, Bocher WO. Risankizumab in patients with moderate to severe Crohn's disease: an open-label extension study. Lancet Gastroenterol Hepatol. 2018 Oct;3(10):671-680. doi: 10.1016/S2468-1253(18)30233-4. Epub 2018 Jul 25.

  PMID: 30056030 DERIVED

• Feagan BG, Sandborn WJ, D'Haens G, Panes J, Kaser A, Ferrante M, Louis E, Franchimont D, Dewit O, Seidler U, Kim KJ, Neurath MF, Schreiber S, Scholl P, Pamulapati C, Lalovic B, Visvanathan S, Padula SJ, Herichova I, Soaita A, Hall DB, Bocher WO. Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn's disease: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 2017 Apr 29;389(10080):1699-1709. doi: 10.1016/S0140-6736(17)30570-6. Epub 2017 Apr 12.

  PMID: 28411872 DERIVED

MeSH Terms

Conditions

Crohn Disease

Interventions

risankizumab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

+1 800 243 0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Period 1 was blinded intravenous (IV) therapy, period 2 was open label IV therapy and period 3 was open label subcutaneous (SC) therapy.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2013
• First Posted: January 9, 2014
• Study Start: February 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: November 1, 2016
• Last Updated: November 23, 2018
• Results First Posted: November 23, 2018

Record last verified: 2018-10