AMG 181 in Subjects with Moderate to Severe Crohn's Disease

Overview

About this study

This is a randomized, double-blind, placebo-controlled, parallel group, multiple dose study to evaluate the efficacy of AMG 181 compared with placebo as measured by the proportion of subjects in remission (CDAI score < 150) at week 8 (primary endpoint). After completing all screening assessments and meeting all eligibility criteria, subjects will be randomized to receive placebo or AMG 181 at various doses per protocol. A maximum of approximately 80% of subjects with any prior anti-TNF agent use will be allowed in the study. At the end of the double blind period, subjects will enter an open-label period during which all subjects will receive open-label AMG 181 at a single dose level according to protocol. Subjects who fail to achieve minimal improvement, or experience disease worsening after initial response are eligible to enter the open-label period early beginning at week 12 or after. Subjects that complete the open-label period or early terminate from the study will enter the 2 year safety follow up period.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Diagnosed with ileal, ileo-colonic, or colonic Crohn's disease for a minimum of 6 months prior to initiating Study Product
  • Moderately to severely active Crohn's disease, as defined by a CDAI score > 220 and <450 at baseline
  • Evidence of active inflammation within 12 weeks prior to baseline
  • Demonstrated an inadequate response to, loss of response to, or intolerance to at least one of the following agents:
    • Immunomodulators and/or Anti-TNF agents
    • corticosteroids (non-US sites only)
  • Neurological exam free of clinically significant, unexplained signs or symptoms during screening and no clinically significant change prior to randomization
  • Subject has no known history of active tuberculosis and has a negative test for tuberculosis during screening

Exclusion Criteria:

  • Short bowel syndrome
  • Stricture with obstructive symptoms within 3 months
  • Bowel surgery within 12 weeks prior baseline, or has planned bowel surgery within 24 weeks from baseline
  • Ileostomy and/or colostomy
  • Any gastric or intestinal pouch
  • Evidence of an infected abscess
  • Bowel perforation or evidence of noninflammatory obstruction during the 6 months
  • Stool positive for C. difficile toxin at screening
  • Any uncontrolled or clinically significant systemic disease
  • Known to have tested positive for hepatitis B virus surface antigen, hepatitis C virus antibody, or HIV
  • Any underlying condition that predisposes subject to infections
  • Subject has malignancy (other than resected cutaneous basal or cutaneous squamous cell carcinoma, or treated in situ cervical cancer considered cured) within 5 years of baseline
  • Received an anti-TNF agent, cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, tacrolimus, topical (rectal) aminosalicylic acid (eg, mesalamine) or topical (rectal) steroids, intravenous or intramuscular corticosteroids within protocol-specified time periods.
  • Any prior exposure to antagonists of integrins or integrin ligands (eg, natalizumab, efalizumab, or vedolizumab), rituximab, or TNF kinoid immunotherapies, AMG 181, or any form of cell-based transplantation
  • Received treatment of infection with intravenous (within 30 days of baseline) or oral (within 14 days prior to baseline) antibiotics, antivirals, or antifungals
  • Significant Laboratory abnormalities
  • Pregnant or breast feeding

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

Edward Loftus, M.D.

Closed for enrollment

More information

Publications

  • Talimogene laherparepvec is a first-in-class intralesional oncolytic immunotherapy. In a recent Phase III trial (OPTiM), talimogene laherparepvec significantly improved durable response rate compared with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF). Overall response rate was also higher in the talimogene laherparepvec arm, and the greatest efficacy was demonstrated in patients with earlier-stage (IIIB, IIIC, or IVM1a) melanoma. Talimogene laherparepvec was well tolerated, with the majority (89%) of adverse events being grade 1 or 2. Preclinical studies have shown that talimogene laherparepvec exerts antitumor activity by selectively replicating within and destroying cancer cells, and through the release of tumor-associated antigens and expression of GM-CSF, which facilitates a wider antitumor immune response. It is hypothesized that combining talimogene laherparepvec with a systemic immunotherapy may, by bringing together complementary mechanisms of action, further enhance the efficacy of both agents. Indeed, talimogene laherparepvec is currently being assessed in combination with immune checkpoint inhibitors, including ipilimumab and pembrolizumab, in trials for melanoma and other solid tumors. Early results in melanoma indicate that the combination of talimogene laherparepvec with ipilimumab or pembrolizumab has greater efficacy than either therapy alone, without additional safety concerns above those expected for each monotherapy. In this review, we discuss the latest results from trials assessing talimogene laherparepvec in combination with other immunotherapies, provide an overview of ongoing and upcoming combination trials, and suggest future directions for talimogene laherparepvec in combination therapy for solid tumors. Read More on PubMed
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