Low dose IL-2 treatment for Crohn's disease

Low Dose IL-2 for the Treatment of Crohn's Disease

This study is testing whether a low-dose treatment with a drug called IL-2 can help people with moderate-to-severe Crohn's disease feel better when other treatments haven't worked.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 12 Years to 80 Years
• Sex: All
• Sponsor: Boston Children's Hospital (Academic / other)
• Drugs / interventions: ustekinumab
• Locations: 3 sites (Boston, Massachusetts and 2 other locations)
• Trial ID: NCT04263831 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and maximum effective dose of low-dose Interleukin-2 (IL-2) in patients with moderate-to-severe Crohn's disease. The study will involve administering daily subcutaneous doses of IL-2 for eight weeks to assess its impact on regulatory T cells and overall disease management. By focusing on the manipulation of Tregs, the trial seeks to provide a new therapeutic approach for patients who have not responded adequately to existing treatments. The study will also monitor the safety profile and potential efficacy of this treatment in the target population.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals aged 12-80 with a diagnosis of moderate-to-severe Crohn's disease who have failed to respond to at least one conventional therapy.

Not a fit: Patients with mild Crohn's disease or those who have not yet tried conventional therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new effective option for patients with Crohn's disease who have not responded to conventional therapies.

How similar studies have performed: Previous studies have shown promise with low-dose IL-2 in other conditions, suggesting potential for success in this novel application for Crohn's disease.

Eligibility criteria

Inclusion Criteria:

1. Age 12-80 years. Maximum age limit for subjects recruited at BCH will be 30 years.
2. A diagnosis of CD made by standard clinical, radiological, endoscopic and histological criteria.

   a. A subset of patients with Ileostomies or colostomies will be permitted.
3. Adult subjects with moderate-to-severe CD (CDAI score 220-450)

   a. a modified CDAI will be used to assess patients with ileostomies/colostomies. Number of liquid stools per day will be substituted for number of bag empties per day.
4. Evidence of endoscopic inflammation accessible via ileocolonoscopy or ileoscopy

   1. Simple Endoscopic Score for CD (SES-CD) ≥ 6 or ≥ 4 for isolated ileal disease
   2. patients with ileostomies will be assessed as patients with isolated ileal disease via SES-CD.
5. Failure to tolerate or failure to respond to at least one conventional therapy with the intention of inducing or maintaining remission (including but not limited to oral corticosteroids, oral 5-aminosalicylates, azathioprine and/or 6-mercaptopurine, TNF alpha antagonist, anti-integrins, ustekinumab). Corticosteroid dependency (inability to taper oral corticosteroids without a recurrence of disease activity) is also included in this category.
6. Stable doses of concomitant medications, as defined in Section 5
7. A negative pregnancy test within 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.
8. The ability of adult participants who are able to make their own healthcare decisions to provide informed consent or the ability of a legal guardian to provide consent if the participant is a child (less than 18 years of age) or has mild intellectual disability and cannot consent for him or herself. In the event that a legal guardian provides consent, the study participant must be able to demonstrate an understanding of the study at his or her comprehension level and must have the ability to give verbal assent. If the legal guardian is court appointed, then the legal guardian must be able to provide documentation of court appointed guardianship.

Exclusion Criteria:

1. A diagnosis of ulcerative colitis or indeterminate colitis.
2. Requirement for immediate surgical, endoscopic or radiological intervention for perforation, sepsis, or intra-abdominal or perianal abscess.
3. History of colorectal cancer or dysplasia.
4. Positive stool test for Clostridium difficile via GDH/EIA two step testing method. PCR only testing will not be accepted. If patient is GDH positive and EIA negative, enrollment will be permitted.
5. Current medically significant infection.
6. Significant laboratory abnormalities;

   1. Hb \< 7.0 g/dL, WBC \< 2.5 x 103/mm3, Plt \< 50 x 103/mm3.
   2. Creatinine ≥ 2x institutional ULN.
   3. Total bilirubin \> 2.0 mg/dL, ALT \> 2x institutional ULN. Elevated unconjugated bilirubin related to Gilbert's syndrome is allowed.
   4. Abnormal thyroid function tests.
7. Positive serology for HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV).
8. Positive screening test for tuberculosis (TB).
9. Treatment with any biologic medication within 4 weeks of first study drug dose (baseline) (see below section on washouts)
10. Received another IND within 5 half-lives of that agent baseline.
11. Malignancy within the last 5 years, excluding non-melanoma skin cancer.
12. Allergy to any component of the study drug.
13. Pregnant or lactating women.
14. Inability to comply with the study protocol or inability of the subject or the subject's legal guardian to provide informed consent.
15. Prior exposure to IL-2.
16. Uncontrolled cardiac angina or symptomatic congestive cardiac failure (NYHA Class III or IV).

Where this trial is running

Boston, Massachusetts and 2 other locations

• Boston Children's Hospital — Boston, Massachusetts, United States (Recruiting)
• Brigham and Women's Hospital — Boston, Massachusetts, United States (Recruiting)
• Mount Sinai — New York, New York, United States (Recruiting)

Study contacts

• Principal investigator: Scott Snapper, MD, PhD — Boston Children's Hospital
• Study coordinator: Heidy Cabral

Conditions Crohn Disease; Inflammatory bowel disease; Interleukin 2; Regulatory T Cells