Crohn Disease
Low-Dose Interleukin-2 for Moderate-to-Severe Crohn’s Disease
This phase 1b/2a study is investigating the safety, maximum effective dose, immune effects, and possible efficacy signal of eight weeks of daily low-dose interleukin-2 injections in people with moderate-to-severe Crohn’s disease.
Registry title: Low Dose IL-2 for the Treatment of Crohn's Disease
3 recruiting U.S. sites ↓Study at a glance
- Age
- 12 Years–80 Years
- Treatment
- Interleukin-2 (aldesleukin).
- Design
- Not provided
- Central study contact
- Delaney Sartwell617-525-7322dsartwell@bwh.harvard.edu
- Sponsor
- Boston Children's Hospital
Research question
What dose of daily low-dose interleukin-2 has the greatest intended effect within the studied dose range while maintaining an acceptable safety profile, and how does treatment affect Crohn’s disease activity and regulatory T cells?
Participant snapshot
Who the study is looking for
- The study is looking for people ages 12 to 80; Boston Children’s Hospital limits enrollment there to age 30 or younger.
- The study is looking for people with Crohn’s disease confirmed using standard clinical, imaging, endoscopic, and tissue criteria.
- Adult participants must have moderate-to-severe disease, defined by a Crohn’s Disease Activity Index score of 220 to 450.
- Participants must have endoscopic inflammation and must have been unable to tolerate or respond to at least one conventional Crohn’s therapy, or be corticosteroid-dependent.
Participation overview
What participation may involve
Participants receive a once-daily injection under the skin of one assigned interleukin-2 dose for eight weeks. The study evaluates adverse events, dose effects, Crohn’s disease activity, inflammation markers, and immune-cell changes. What participation may involve: - Receive interleukin-2 by injection under the skin once daily for eight weeks. - Be monitored for serious and non-serious adverse events and dose-limiting toxicities. - Have Crohn’s disease activity assessed using the Crohn’s Disease Activity Index and inflammation markers including fecal calprotectin or C-reactive protein. - Have immune-cell changes assessed in peripheral blood and intestinal tissue from the lamina propria. The treatment course lasts eight weeks. The registry reports immune-response assessment during treatment and for four weeks after treatment stops.
Study interventions
What participants may receive or do
- Interleukin-2 (aldesleukin).: Participants receive aldesleukin, also called interleukin-2 or Proleukin, as an injection under the skin once daily for eight weeks. The registry describes two dose cohorts, with each participant remaining at one dose level.
Study design
How the comparison works
This is an open-label, single-group phase 1/2 study with an estimated enrollment of 30 participants. All participants are assigned to the experimental interleukin-2 arm, which contains two dose cohorts. The registry marks allocation as not applicable and describes a single treatment group; it does not report random assignment. The study has no masking, meaning participants and study staff are not described as blinded to the assigned treatment. The registry describes one experimental treatment arm and does not list a separate comparison or control arm.
Reported activities
Procedures and tests
- Once-daily interleukin-2 injections under the skin for eight weeks.
- Monitoring and recording of serious adverse events, non-serious adverse events, and dose-limiting toxicities.
- Crohn’s Disease Activity Index assessments for clinical disease activity.
- Fecal calprotectin or C-reactive protein measurements to assess inflammatory response.
- Immune-cell measurements in peripheral blood and intestinal lamina propria tissue.
- Screening must confirm endoscopic inflammation accessible by ileocolonoscopy or ileoscopy and meeting the specified Simple Endoscopic Score for Crohn’s Disease threshold.
- Screening criteria include blood counts, creatinine, bilirubin, alanine aminotransferase, and thyroid-function results.
- Screening criteria include testing for Clostridium difficile, human immunodeficiency virus, hepatitis B, hepatitis C, and tuberculosis.
- Participants of child-bearing potential must have a negative pregnancy test within two weeks before the expected first study-drug dose.
Eligibility highlights
Details that may affect whether you contact the study
These are selected highlights, not a complete eligibility check. Exact criteria remain in the full registry record below.
Common requirements
- Participants must be ages 12 to 80, although Boston Children’s Hospital enrolls only people age 30 or younger.
- Crohn’s disease must have been diagnosed using standard clinical, imaging, endoscopic, and tissue criteria.
- Adult participants must have moderate-to-severe Crohn’s disease, defined as a Crohn’s Disease Activity Index score from 220 to 450.
- Endoscopic inflammation must be reachable by ileocolonoscopy or ileoscopy and meet the stated Simple Endoscopic Score for Crohn’s Disease threshold.
- Participants must have been unable to tolerate or respond to at least one conventional therapy intended to induce or maintain remission, or must be corticosteroid-dependent.
- Concomitant medications must be at stable doses as defined elsewhere in the study protocol.
- Participants who could become pregnant need a negative pregnancy test within two weeks before starting study drug; participants of reproductive potential must use acceptable birth control during treatment and for six months afterward.
- Adults able to make their own healthcare decisions must provide informed consent; specified guardian-consent and participant-assent requirements apply to children and certain participants with mild intellectual disability.
Possible reasons someone may not be able to join
- People diagnosed with ulcerative colitis or indeterminate colitis are excluded.
- People needing immediate surgery, endoscopy, or radiological intervention for perforation, sepsis, or an abdominal or perianal abscess are excluded.
- A history of colorectal cancer or dysplasia excludes participation.
- A positive Clostridium difficile stool result by the specified two-step method excludes participation, except that enrollment is permitted when GDH is positive and EIA is negative.
- A current medically significant infection excludes participation.
- The listed abnormalities in blood counts, kidney function, liver tests, or thyroid function exclude participation, subject to the stated Gilbert’s syndrome exception.
- Positive testing for human immunodeficiency virus, hepatitis B, hepatitis C, or tuberculosis excludes participation.
- Treatment with any biologic medication within four weeks before the first study-drug dose excludes participation.
- Receiving another investigational new drug within five half-lives of that agent before baseline excludes participation.
- Pregnant or breastfeeding women are excluded, as are people with prior interleukin-2 exposure.
- Uncontrolled cardiac angina or symptomatic New York Heart Association class III or IV congestive heart failure excludes participation.
Important unknowns
What the record does not make clear
- The registry does not state how many in-person or remote visits are required or when they occur.
- The registry requires stable concomitant medication doses but refers to a protocol section that is not included in this record.
- The record gives a four-week exclusion window for biologics and a five-half-life window for another investigational drug, but it references additional washout information that is not present.
- The registry does not explain what treatment is available if Crohn’s disease worsens during the study.
- Endoscopic inflammation is required, and immune cells in intestinal tissue are assessed, but the record does not clearly state whether or how often the study performs ileocolonoscopy, ileoscopy, or biopsy.
- The registry does not state which study-related or routine-care costs are covered or billed to insurance.
- The registry does not report whether participants receive compensation.
- The registry does not report reimbursement or support for transportation, lodging, meals, or parking.
- The registry does not state whether any visits or assessments can be completed remotely.
- The registry does not describe access to interleukin-2 after study treatment ends.
Before contacting the site
Questions for the study team
- How many study visits are required, where do they occur, and how long does each visit usually take?
- Will participants need new endoscopies or intestinal biopsies, and at what points in the study?
- Which current Crohn’s medications can continue, and what stability or washout period applies to each one?
- What happens if symptoms or inflammation worsen during treatment, and what rescue treatments are allowed?
- What blood, stool, pregnancy, infection, and immune-cell tests are performed, and how often are samples collected?
- Which study-related costs are covered, and are compensation or travel assistance available?
- Are any visits or follow-up activities available remotely?
Before changing care
Questions for your gastroenterologist
- How stable is my Crohn’s disease now, and what risks could arise if my current treatment must be held or changed for screening?
- What approved treatment alternatives remain reasonable for my disease history before I consider a research study?
- Do my infection history, laboratory results, heart health, or prior treatments raise particular concerns about this study?
- How should my gastroenterology team and the research team coordinate medication decisions, disease monitoring, and care if my Crohn’s disease worsens?
This plain-language digest is provided by the Aidy clinical trials API. It may omit details and is not medical advice or an eligibility decision. Review the full registry record and confirm details with the study team.
Source record
Full registry record
The sections below preserve the study information supplied through ClinicalTrials.gov, including complete descriptions, criteria, outcomes, and locations.
About this study
The purpose of this study is to determine the safety and maximum effective dose (MED) of Interleukin-2 in subjects with moderate-to-severe crohn's disease.
Despite recent advances in treatment, a significant proportion of patients with Crohn's disease have suboptimal responses to medical therapy, leaving an urgent need to identify new therapies. One promising new approach to treat IBD is through the manipulation of regulatory T cells (Tregs). Tregs are an immune modulating subset of CD4+ lymphocytes that antagonize the activation and effector function of multiple immune cell types and promote tolerance to self-antigens. Adoptively transferred Tregs are effective in murine models of IBD. An alternative approach to disease management through Treg manipulation is to increase Treg numbers in vivo. Interleukin-2 (IL-2, Proleukin®) is a T cell growth factor. IL-2 is currently licensed for the treatment of metastatic renal cell carcinoma and metastatic melanoma. At low doses, IL-2 promotes the selective activation and expansion of Tregs in humans. Tregs constitutively express CD25, a component of the high-affinity IL-2R, while CD25 is only transiently expressed by activated conventional T effector cells. Low-dose (LD) IL-2 selectively expands Tregs in humans and is safe in chronic GvHD and other phase 1 and 2 clinical trials. This is a phase 1b/2a clinical trial to assess the safety and the efficacy of LD SC IL-2 for the treatment of CD utilizing daily sc LD IL-2 for 8 weeks in CD patients to determine the maximum effective dose (MED) and safety profile, and to assess a signal of efficacy. We aim to determine in CD patients whether sc LD IL-2 modulates peripheral blood and lamina propria Tregs in vivo and correlates with clinical outcome. We will perform deep immunophenotyping in CD patients treated with LD IL-2 and comprehensively assess the effects of LD IL-2 on CD4+ Tregs and other immune cells in both peripheral and mucosal compartments, and correlate changes in immune phenotype with clinical outcome. Overall this trial is designed to determine the MED and safety profile of LD IL-2 in CD, to obtain a signal of efficacy, and to assess mechanistic underpinnings.
Study design and administration
- Organization
- Boston Children's Hospital
- Organization class
- Other
- Organization study ID
- IRB-P00032653
- Lead sponsor
- Boston Children's Hospital
- Sponsor class
- Other
- Enrollment type
- Estimated
- Allocation
- Na
- Intervention model
- Single Group
- Primary purpose
- Treatment
- Masking
- None
- Who is masked
- Not provided
- Standard age groups
- Child, Adult, Older Adult
Study arms
Experimental
Interleukin-2
Study drug: Interleukin-2 (aldesleukin, Proleukin, IL-2). Each subject will receive an 8-week course of once-daily, subcutaneously administered IL-2. There will be two dose cohorts. Each subject will be recruited into a single dose cohort and receive a single dose level of IL-2 throughout the study. The dose levels will be as follows: Cohort 1: 1.0x10\^6 IU/m\^2/day. Cohort 2: 1.25x10\^6 IU/m\^2/day.
Interventions: Drug: Interleukin-2 (aldesleukin).
Interventions
Drug
Interleukin-2 (aldesleukin).
Description of intervention is covered in "Arm", above.
Eligibility
12 Years–80 Years
All
Not accepted
Inclusion criteria (12)
- Age 12-80 years. Maximum age limit for subjects recruited at BCH will be 30 years.Registry-derived · unreviewed
- A diagnosis of CD made by standard clinical, radiological, endoscopic and histological criteria.Registry-derived · unreviewed
- A subset of patients with Ileostomies or colostomies will be permitted.Registry-derived · unreviewed
- Adult subjects with moderate-to-severe CD (CDAI score 220-450)Registry-derived · unreviewed
- 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.Registry-derived · unreviewed
- Evidence of endoscopic inflammation accessible via ileocolonoscopy or ileoscopyRegistry-derived · unreviewed
- Simple Endoscopic Score for CD (SES-CD) ≥ 6 or ≥ 4 for isolated ileal diseaseRegistry-derived · unreviewed
- patients with ileostomies will be assessed as patients with isolated ileal disease via SES-CD.Registry-derived · unreviewed
- 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.Registry-derived · unreviewed
- Stable doses of concomitant medications, as defined in Section 5Registry-derived · unreviewed
- 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.Registry-derived · unreviewed
- 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.Registry-derived · unreviewed
Exclusion criteria (20)
- A diagnosis of ulcerative colitis or indeterminate colitis.Registry-derived · unreviewed
- Requirement for immediate surgical, endoscopic or radiological intervention for perforation, sepsis, or intra-abdominal or perianal abscess.Registry-derived · unreviewed
- History of colorectal cancer or dysplasia.Registry-derived · unreviewed
- 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.Registry-derived · unreviewed
- Current medically significant infection.Registry-derived · unreviewed
- Significant laboratory abnormalities;Registry-derived · unreviewed
- Hb \< 7.0 g/dL, WBC \< 2.5 x 103/mm3, Plt \< 50 x 103/mm3.Registry-derived · unreviewed
- Creatinine ≥ 2x institutional ULN.Registry-derived · unreviewed
- Total bilirubin \> 2.0 mg/dL, ALT \> 2x institutional ULN. Elevated unconjugated bilirubin related to Gilbert's syndrome is allowed.Registry-derived · unreviewed
- Abnormal thyroid function tests.Registry-derived · unreviewed
- Positive serology for HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV).Registry-derived · unreviewed
- Positive screening test for tuberculosis (TB).Registry-derived · unreviewed
- Treatment with any biologic medication within 4 weeks of first study drug dose (baseline) (see below section on washouts)Registry-derived · unreviewed
- Received another IND within 5 half-lives of that agent baseline.Registry-derived · unreviewed
- Malignancy within the last 5 years, excluding non-melanoma skin cancer.Registry-derived · unreviewed
- Allergy to any component of the study drug.Registry-derived · unreviewed
- Pregnant or lactating women.Registry-derived · unreviewed
- Inability to comply with the study protocol or inability of the subject or the subject's legal guardian to provide informed consent.Registry-derived · unreviewed
- Prior exposure to IL-2.Registry-derived · unreviewed
- Uncontrolled cardiac angina or symptomatic congestive cardiac failure (NYHA Class III or IV).Registry-derived · unreviewed
This information can identify a possible match, conflict, or item needing confirmation. Only the study team can determine eligibility.
Study outcomes
Primary outcome
Number of subjects with serious and non-serious adverse events.
Time frame: 8 weeks
Enumeration of the serious and non-serious adverse events seen in the study. Enumeration of any dose limiting toxicity seen in the study.
Primary outcome
Maximum effective dose
Time frame: 8 weeks
Identification of the dose cohort at which the MED occurs.
Secondary outcome
Clinical Response
Time frame: 8 weeks
This is a composite endpoint. CDAI scores will be used to assess clinical activity. Moderate to severe CD, denoted by a CDAI score 220-450, is an inclusion criterion. Definition of Clinical Response. CDAI-100 response (≥100-point decrease in the CDAI score) at week 8 Composite Outcome: Clinical response and at least a 50% decrease in fecal calprotectin or CRP
Secondary outcome
Immunological Response
Time frame: 12 weeks
Enumeration of the number of subjects with a change in the absolute number of immune cells in the peripheral blood and lamina propria of subjects during the 8 weeks of treatment, and during the 4 weeks following cessation of treatment.
Recruiting locations in the United States
Boston Children's Hospital
RecruitingBoston, Massachusetts, 02115, United States
Richelle L Bearup, MPH617-919-4592richelle.bearup@childrens.harvard.edu
Daniel Ironson617-919-4592Daniel.ironson@childrens.harvard.edu
Scott Snapper, MD, PhD
Brigham and Women's Hospital
RecruitingBoston, Massachusetts, 02115, United States
Delaney Sartwell617-525-7322dsartwell@bwh.harvard.edu
Jessica Allegretti, MD, MPH
Mount Sinai
RecruitingNew York, New York, 10029, United States
Sari Feldman212-824-7669sari.feldman@mssm.edu
Jean Fred Colombel, MD
Central study contacts
Registry dates
- First posted
- Feb 11, 2020
- Primary completion
- Jun 30, 2027
- Overall completion
- Dec 30, 2027
Trial information comes from ClinicalTrials.gov and may change. Confirm current status, eligibility, and site details with the study team. Aidy does not provide medical advice or determine eligibility.