Study to Evaluate Safety, Tolerability and Efficacy of GSK2330811 in Crohn's Disease

NCT04151225 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 208482
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The study will include participants with moderate to severe Crohn's disease. The aim is to evaluate the safety, tolerability, and efficacy of anti-oncostatin M monoclonal antibody (mAb) GSK2330811. This is a parallel group study with Induction and Maintenance periods. During Induction, the first 100 participants randomised will receive a 450mg GSK2330811 SC loading dose followed by 150mg weekly (Q1W), or placebo for 12 weeks. Additional dose-ranging arms will open after the 100th participant is randomized and in addition to placebo and the highest dose arms will also include a 300mg subcutaneous (SC) loading dose followed by 150mg SC every 2 weeks (Q2W) arm, a 300mg loading dose followed by 150mg SC every 4 weeks (Q4W) arm and a 150mg SC every 8 weeks (Q8W) arm. Participants with a clinical response at Week 12 will continue into a 40-week blinded maintenance period and will receive either 150mg SC Q2W, 150mg SC Q4W, 150mg SC Q8W or placebo. Participants without a clinical response at Week 12 will be offered up to 40 weeks of open label treatment with GSK2330811. Approximately 560 participants will be screened to randomize 280.

Conditions

Crohn's Disease

Keywords

Monoclonal antibody; Crohns Disease; Oncostatin M; GSK2330811

Outcome Measures

Primary Outcomes (1)

• Percentage of participants with endoscopic response measured by Simple Endoscopic score for Crohn's Disease (SES-CD) at Week 12

  The SES-CD is a validated tool for grading the endoscopic severity of active Crohn's disease based on an assessment of the size of individual ulcers, the proportion of the surface that is abnormal and the proportion of the surface that is ulcerated, and the presence or absence of visible stenosis. The attributes are scored across 5 bowel segments and combined to give an SES-CD score ranging from 0 to 56 (higher scores represent more severe endoscopic disease involvement). SES-CD will be determined for each endoscopy using a central reading algorithm. Endoscopic response is defined as \>= 50 percent decrease from Baseline in SES-CD

  Week 12

Secondary Outcomes (14)

• Percentage of participants with endoscopic response based on dose response relationship at Week 12 measured by SES-CD

  Week 12

• Change from Baseline in SES-CD at Week 12

  Baseline (within 35 days prior to Day 1) and Week 12

• Percentage of participants in endoscopic remission at Week 12

  Week 12

• Percentage of participants with absence of mucosal ulceration on endoscopy at Week 12

  Week 12

• Percentage of participants with clinical response measured by Patient Reported Outcome 2 (PRO2) at Week 12

  Week 12

Other Outcomes (9)

• Number of participants with serious adverse events (SAEs)

  Up to Week 68

• Number of participants with adverse events (AEs) and Adverse Event of Special Interest (AESI)

  From Week 0 (Day 1) to Week 68

• Number of participants with clinically significant changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP)

  Week 0 (Day 1) to Week 68

Study Arms (5)

Participants receiving placebo

PLACEBO COMPARATOR

Participants will receive placebo loading dose followed by placebo for 12 weeks during Induction phase. Participants with clinical response at Week 12 will continue to receive placebo into a 40-weeks blinded maintenance period. Participants without a clinical response at Week 12 will receive a 450mg GSK2330811 SC loading dose at Week 12, followed by 150 mg SC every week from Week 13 until Week 23, followed by 150 mg SC every 2 weeks until Week 50.

Drug: Placebo

Participants receiving GSK2330811 450mg loading dose/150mg Q1W

EXPERIMENTAL

Participants will receive 450mg GSK2330811 SC as loading dose followed by 150 mg GSK2330811 Q1W for 12 weeks during Induction period. Participants with clinical response at Week 12 will continue into a 40 weeks blinded maintenance period will receive 150 mg GSK2330811 SC Q2W. Participants without a clinical response will receive GSK2330811 150mg Q1W from Week 12 until Week 23, followed by GSK2330811 150mg Q2W until Week 50.

Drug: GSK2330811

Participants receiving GSK2330811 300mg loading dose/150mg Q2W

EXPERIMENTAL

Participants will receive 300mg GSK2330811 SC as loading dose followed by 150mg GSK2330811 SC Q2W for 12 weeks during Induction period. Participants with clinical response at Week 12 will continue into a 40 weeks blinded maintenance period will receive 150mg GSK2330811 SC Q2W. Participants without a clinical response will receive GSK2330811 150mg Q1W from Week 12 until Week 23, followed by GSK2330811 150mg Q2W until Week 50.

Drug: GSK2330811

Participants receiving GSK2330811 300mg loading dose/150mg Q4W

EXPERIMENTAL

Participants will receive 300mg GSK2330811 SC as loading dose followed by 150mg GSK2330811 SC Q4W for 12 weeks during Induction period. Participants with clinical response at Week 12 will continue into a 40 weeks blinded maintenance period will receive 150 mg GSK2330811 SC Q4W. Participants without a clinical response will receive GSK2330811 150mg Q1W from Week 12 until Week 23, followed by GSK2330811 150mg Q2W until Week 50.

Drug: GSK2330811

Participants receiving GSK2330811 150mg Q8W

EXPERIMENTAL

Participants will receive GSK2330811 SC 150 mg Q8W for 12 weeks during Induction period. Participants with clinical response at Week 12 will continue into a 40 weeks blinded maintenance period will receive 150 mg GSK2330811 SC Q8W. Participants without a clinical response will receive GSK2330811 150mg Q1W from Week 12 until Week 23, followed by GSK2330811 150mg Q2W until Week 50.

Drug: GSK2330811

Interventions

GSK2330811 DRUG

GSK2330811 will be available as SC injection with a unit dose strength of 150 mg/mL. GSK2330811 will be available in single-use pre-filled syringe.

Participants receiving GSK2330811 150mg Q8W; Participants receiving GSK2330811 300mg loading dose/150mg Q2W; Participants receiving GSK2330811 300mg loading dose/150mg Q4W; Participants receiving GSK2330811 450mg loading dose/150mg Q1W

Placebo DRUG

Placebo will be available as SC injection of 0.9 percent saline solution. It will be available as single-use pre-filled syringe.

Participants receiving placebo

Eligibility Criteria

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

You may qualify if:

• Participant must be 18 years of age or over at the time of signing the informed consent.
• Participants who have a diagnosis of Crohn's Disease, established at least 3 months prior to first screening visit, supported by radiologic, histologic and/or endoscopic findings, and are expected to be able to be managed on an outpatient basis, if clinical course does not worsen.
• Participants who have active colitis and/or ileitis at screening, confirmed by centrally-read ileo-colonoscopy, defined as a baseline SES-CD score of \>= 7 (\>= 4 if disease confined to the terminal ileum) and \<=35.
• Participants who have active clinical disease at Baseline, measured by PRO2, defined as a 7-day average SF \>= 4 and/or a 7-day average AP \>=2.
• Participants who have a history of at least one of the following: Inadequate response to, loss of response to, or intolerance to conventional immunosuppression (i.e. azathioprine, 6-mercaptopurine, methotrexate); Inadequate response to, loss of response to, intolerance to, or demonstrated dependence on oral corticosteroids; Inadequate response to, loss of response to, or intolerance to biologic therapy or small molecule JAK inhibitors.
• Participants with Baseline body mass index (BMI) \>= 18.5 kilogram per square meter (kg/m\^2).
• Male and Female participants are both eligible to participate.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or A WOCBP who agrees to use a contraceptive method that is highly effective, with a failure rate of \<1 percent, from 28 days prior to first dosing day (Day 1), during the dosing period and for at least 126 days (18 weeks) after the last dose of study treatment, corresponding to the time needed to eliminate any study intervention. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
• Participant who is capable of giving signed informed consent.

You may not qualify if:

• Participants with a current diagnosis of indeterminate colitis, inflammatory bowel disease (unclassified), infectious colitis, lymphocytic colitis, microscopic colitis, radiation colitis, ischemic colitis or ulcerative colitis.
• Participants with complications of Crohn's disease including strictures, adhesions, stenosis, short bowel syndrome and any other manifestation, if it is anticipated to require surgery during the study or that could interfere with study assessments (including but not limited to symptomatic strictures or stenosis) or that may confound the evaluation of benefit from treatment with GSK2330811.
• A current ileostomy or colostomy.
• Any bowel resection or diversion within 6 months or other intra-abdominal surgery within 3 months prior to the screening ileo-colonoscopy.
• Receiving tube feeding, defined formula diets, or total parenteral nutrition within 4 weeks prior to the screening ileo-colonoscopy.
• Current or prior abscess (proven or suspected) unless drained and adequately treated at least 3 weeks prior to the screening ileo-colonoscopy for cutaneous and perianal abscesses and at least 8 weeks prior to the screening ileo-colonoscopy for intra-abdominal abscesses. There must be no anticipated need for further surgery during the study.
• Active fistulas associated with an abscess and anticipated need for surgery during the study. If a fistula is present, it should have established drainage.
• Prior fecal micro-biota transplant within 3 months prior to the screening ileo-colonoscopy.
• Participants with any uncontrolled medical conditions, other than active Crohn's Disease, that in the opinion of the investigator puts the participant at unacceptable risk or likely will interfere with study assessments or data integrity. Other medical conditions should be stable at the time of screening expected to remain stable for the duration of the study.
• Known history of or current bleeding or coagulation disorder.
• Current or chronic history of liver or biliary disease (except for Gilbert's syndrome, asymptomatic gallstones or uncomplicated fatty liver disease).
• A major organ transplant (example heart, lung, kidney, liver, pancreas) or hematopoietic stem cell/marrow transplant.
• Unstable lifestyle factors, such as alcohol use to excess or recreational drug use, to the extent that in the opinion of the investigator would interfere with the ability of a participant to complete the study.
• Major surgery within 3 months prior to the first screening visit or planned during the study.
• Cancer or carcinoma in situ present within the last 5 years, except for adequately treated non-metastatic basal or squamous cell cancers of the skin or carcinoma in situ of the uterine cervix that has been fully treated and shows no evidence of recurrence.

Sponsors & Collaborators

• GlaxoSmithKline: lead

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This is a double blind study where participants, investigator and sponsor will be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a parallel group treatment study.

Study Record Dates

• First Submitted: November 4, 2019
• First Posted: November 5, 2019
• Study Start: April 5, 2021
• Primary Completion: April 22, 2024
• Study Completion: May 26, 2025
• Last Updated: January 14, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.