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

NCT ID: NCT04263831

Last Updated: 2025-04-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-11

Study Completion Date

2025-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Crohn Disease

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Interleukin-2 (aldesleukin).

Intervention Type DRUG

Description of intervention is covered in "Arm", above.

Interventions

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Interleukin-2 (aldesleukin).

Description of intervention is covered in "Arm", above.

Intervention Type DRUG

Eligibility Criteria

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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).
Minimum Eligible Age

12 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

Boston Children's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Scott B. Snapper, MD PHD

Chief, Gastroenterology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Scott Snapper, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Boston Children's Hospital

Jessica Allegretti, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hosptial

Locations

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Boston Children's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Mount Sinai

New York, New York, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Heidy Cabral

Role: CONTACT

617-525-7322

Richelle L Bearup, MPH

Role: CONTACT

617-919-4592

Facility Contacts

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Ashrita Iyengar

Role: primary

617-919-4592

Richelle L Bearup, MPH

Role: backup

617-919-4592

Heidy Cabral

Role: primary

617-525-7322

Sari Feldman

Role: primary

212.824.7669

References

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Koreth J, Matsuoka K, Kim HT, McDonough SM, Bindra B, Alyea EP 3rd, Armand P, Cutler C, Ho VT, Treister NS, Bienfang DC, Prasad S, Tzachanis D, Joyce RM, Avigan DE, Antin JH, Ritz J, Soiffer RJ. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011 Dec 1;365(22):2055-66. doi: 10.1056/NEJMoa1108188.

Reference Type BACKGROUND
PMID: 22129252 (View on PubMed)

Matsuoka K, Koreth J, Kim HT, Bascug G, McDonough S, Kawano Y, Murase K, Cutler C, Ho VT, Alyea EP, Armand P, Blazar BR, Antin JH, Soiffer RJ, Ritz J. Low-dose interleukin-2 therapy restores regulatory T cell homeostasis in patients with chronic graft-versus-host disease. Sci Transl Med. 2013 Apr 3;5(179):179ra43. doi: 10.1126/scitranslmed.3005265.

Reference Type BACKGROUND
PMID: 23552371 (View on PubMed)

Saadoun D, Rosenzwajg M, Joly F, Six A, Carrat F, Thibault V, Sene D, Cacoub P, Klatzmann D. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med. 2011 Dec 1;365(22):2067-77. doi: 10.1056/NEJMoa1105143.

Reference Type BACKGROUND
PMID: 22129253 (View on PubMed)

Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987 Dec 24;317(26):1625-9. doi: 10.1056/NEJM198712243172603.

Reference Type BACKGROUND
PMID: 3317057 (View on PubMed)

Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. doi: 10.1056/NEJMoa050516.

Reference Type BACKGROUND
PMID: 16339095 (View on PubMed)

Other Identifiers

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R01DK126448

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB-P00032653

Identifier Type: -

Identifier Source: org_study_id

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