Low Dose IL-2 for Ulcerative Colitis
Condition: Ulcerative Colitis
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Intervention: Interleukin-2 (aldesleukin).
Intervention description: Description of intervention is covered in "Arm", above.
Intervention MeSH terms: Aldesleukin; Interleukin-2
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Ulcerative colitis; Inflammatory bowel disease; Interleukin 2; Interleukin-2; IL-2; Regulatory T Cells; Tregs; T-Lymphocytes, Regulatory

Summary:

      The purpose of this study is to determine the safety and maximum effective dose (MED) of
      Interleukin-2 in subjects with moderate-to-severe ulcerative colitis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 18-70 years.

          -  A diagnosis of UC made by standard clinical, radiological, endoscopic and histological
             criteria.

          -  Moderate to severe UC with a Mayo score of 6-12.

          -  Failure to tolerate or failure to respond to at least one conventional therapy with
             the intention of inducing or maintaining remission (examples include oral
             corticosteroids, oral 5-aminosalicylates, azathioprine and/or 6-mercaptopurine, or a
             tumor necrosis factor (TNF) antagonist). Corticosteroid dependency (inability to taper
             oral corticosteroids without a recurrence of disease activity) is also included in
             this category.

          -  Stable doses of concomitant medications.

          -  A negative pregnancy test in the 2 weeks prior to anticipated commencement of the
             study drug, in female subjects of child-bearing age. Men and women of reproductive
             potential must agree to use an acceptable method of birth control during treatment and
             for six months after completion of treatment.

          -  Ability to provide informed consent.

        Exclusion Criteria:

          -  A diagnosis of Crohn's disease or Inflammatory Bowel Disease - Unspecified (IBD-U, a
             diagnostic classification formerly termed "indeterminate colitis").

          -  Requirement for immediate surgical, endoscopic or radiological intervention for toxic
             megacolon, massive hemorrhage, perforation, sepsis, or intra-abdominal or perianal
             abscess.

          -  Ileostomy, proctocolectomy or subtotal colectomy with ileorectal anastomosis.

          -  History of colorectal cancer or dysplasia.

          -  Positive stool test for Clostridium difficile.

          -  Current medically significant infection.

          -  Significant laboratory abnormalities, including;

               1. Hb < 8.0 g/dL, WBC < 2.5 x 103/mm3, Plt < 100 x 103/mm3.

               2. Creatinine ≥ 1.5x institutional upper limit of normal (ULN).

               3. Total bilirubin > 2.0 mg/dL, ALT > 2x institutional ULN, GGT > 2x institutional
                  ULN. Elevated unconjugated bilirubin related to Gilbert's syndrome is allowed.

               4. Abnormal thyroid function tests.

          -  Positive serology for HIV, hepatitis B virus (HBV) or HCV.

          -  Positive screening test for tuberculosis (TB).

          -  First dose of an anti-TNF medication within 4 weeks of anticipated study commencement,
             or a subsequent dose within 2 weeks of commencement; or ciclosporin or tacrolimus
             within 2 weeks of anticipated study commencement.

          -  Received another investigational new drug (IND) within 5 half-lives of that agent
             before the planned commencement of SC IL-2.

          -  Malignancy within the last 5 years.

          -  Allergy to any component of the study drug.

          -  Pregnant or lactating women.

          -  Inability to comply with the study protocol or inability to give informed consent.

          -  Prior exposure to IL-2.

          -  Uncontrolled cardiac angina or symptomatic congestive cardiac failure (NYHA Class III
             or IV).