Low Dose IL-2 for Crohn's Disease

Recruiting at 2 trial locations

Overseen By Heidy Cabral

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Boston Children's Hospital

Must not be taking: Biologics

Disqualifiers: Ulcerative colitis, Cancer, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to find a safe and effective dose of Interleukin-2 (IL-2, also known as Aldesleukin or PROLEUKIN) for individuals with moderate-to-severe Crohn's disease, which causes inflammation in the digestive tract. Participants will receive daily injections of Interleukin-2 for eight weeks at one of two dosage levels. The trial seeks participants who have not found success with other treatments, experience frequent symptoms, and can confirm inflammation through an endoscopy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this potentially groundbreaking therapy.

Will I have to stop taking my current medications?

The trial requires that you have stable doses of your current medications. However, if you are taking any biologic medication, you must stop it at least 4 weeks before starting the study drug.

Is there any evidence suggesting that Interleukin-2 is likely to be safe for humans?

Studies have shown that low-dose Interleukin-2 (IL-2) is generally safe for treating conditions like inflammatory diseases. Research indicates that IL-2 reduces inflammation by boosting the activity of certain immune cells called Tregs, which help calm the immune system. Although the FDA has approved IL-2 for other uses, such as treating certain cancers, side effects like fever and fatigue have been reported, usually with higher doses.

Earlier trials using lower doses, similar to those considered for Crohn's disease, demonstrated a promising safety record. This suggests that low-dose IL-2 might cause fewer and milder side effects. As the current trial is in its early stages, researchers are primarily focused on confirming these safety findings and determining the best dose to use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Crohn's disease?

Most treatments for Crohn's Disease, such as corticosteroids and immunosuppressants, focus on controlling inflammation and suppressing the immune system. But Interleukin-2 (IL-2) works differently by boosting the immune system's regulatory T cells, which help maintain balance and prevent excessive inflammation. This unique mechanism of action could offer better control over the disease with potentially fewer side effects. Researchers are excited because IL-2 might provide a new way to manage Crohn's Disease by enhancing the body's natural ability to regulate its immune response.

What evidence suggests that Interleukin-2 might be an effective treatment for Crohn's disease?

Research has shown that Interleukin-2 (IL-2) may help treat Crohn's disease. In one study, 52.6% of patients who completed an 8-week treatment experienced symptom improvement, and 21.1% of these patients saw their symptoms nearly disappear. IL-2 strengthens the immune system, potentially reducing inflammation in Crohn's disease. These findings suggest IL-2 could be a useful treatment option. Participants in this trial will receive an 8-week course of once-daily, subcutaneously administered IL-2, with two different dose cohorts under study. ^{1 5 6 7 8}

Who Is on the Research Team?

Scott Snapper, MD, PhD

Principal Investigator

Boston Children's Hospital

Jessica Allegretti, MD, MPH

Principal Investigator

Brigham and Women's Hosptial

Are You a Good Fit for This Trial?

Adults aged 18-80 with moderate-to-severe Crohn's Disease, not responding to conventional therapies, can join this trial. They must have endoscopic inflammation and no recent biologic medication use. Exclusions include other bowel diseases, significant infections or lab abnormalities, certain cancers within 5 years, pregnancy, and inability to consent.

Inclusion Criteria

My Crohn's disease is moderate to severe.

I have not improved with standard treatments for my condition.

Evidence of endoscopic inflammation accessible via ileocolonoscopy or ileoscopy

Exclusion Criteria

I have had cancer other than non-melanoma skin cancer in the last 5 years.

I do not have any serious infections right now.

Significant laboratory abnormalities;

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an 8-week course of once-daily, subcutaneously administered IL-2 to determine the maximum effective dose and safety profile

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in immune cells

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Interleukin-2

Trial Overview The trial is testing the safety and maximum effective dose of Interleukin-2 (aldesleukin) for treating Crohn's Disease. It aims to find out how well it works in patients who haven't had success with standard treatments.

How Is the Trial Designed?

Group I: Interleukin-2 Experimental Treatment 1 Intervention

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.

Interleukin-2 is already approved in United States, European Union for the following indications:

Approved in United States as Aldesleukin for:

• Metastatic melanoma
• Metastatic renal cell carcinoma

Approved in European Union as PROLEUKIN for:

• Metastatic renal cell carcinoma

Who Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

Recombinant interleukin-2 (IL-2) therapies, such as aldesleukin, can induce immune responses that lead to tumor reduction, achieving objective response rates of about 20% in metastatic renal cell carcinoma and 13% in metastatic malignant melanoma, with higher rates when combined with other treatments.

While IL-2 is biologically similar to native IL-2 and generally safe, high-dose therapy can cause severe adverse effects across multiple organ systems, necessitating careful monitoring and potential dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-2. A review of its pharmacological properties and therapeutic use in patients with cancer. Whittington, R., Faulds, D.[2018]

Aldesleukin, a treatment for metastatic renal cell carcinoma and melanoma, has been associated with severe systemic toxicity, which has limited its use.

This study reports the first confirmed case of an immediate systemic hypersensitivity reaction to aldesleukin, identified through specific immunoglobulin E testing, highlighting a previously unrecognized safety concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypersensitivity to aldesleukin (interleukin-2 and proleukin) presenting as facial angioedema and erythema. Abraham, D., McGrath, KG.[2016]

High-dose interleukin-2 (IL-2) therapy in 10 children with refractory solid tumors resulted in severe but reversible side effects, including fever and a significant decrease in quality of life as measured by Karnofsky score.

Despite the severe side effects, IL-2 therapy was effective in rescuing five out of ten patients with poor prognosis, indicating its potential as a therapeutic option for difficult-to-treat pediatric cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of high-dose interleukin-2 in heavily pretreated pediatric cancer patients. Schwinger, W., Klass, V., Benesch, M., et al.[2020]

Localized necrosis or perforation of the colon is a rare but serious complication occurring in 1.3% of patients receiving high-dose Interleukin-2 (IL-2) treatment, with gastrointestinal side effects affecting 85% of patients.

All four patients who experienced this complication underwent successful surgical intervention and were able to safely receive IL-2 treatment again after recovery, suggesting that while the risk exists, effective management and retreatment are possible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colonic perforation. An unusual complication of therapy with high-dose interleukin-2. Schwartzentruber, D., Lotze, MT., Rosenberg, SA.[2019]

In a Phase I study involving seven children with advanced cancers, low-dose recombinant human interleukin-2 (rIL-2) (1 X 10(6) U/m2) was found to be safe with no life-threatening toxicity, while high-dose rIL-2 (3 X 10(6) U/m2) caused significant cardiovascular toxicity in two patients, leading to treatment termination.

The study revealed that rIL-2 treatment resulted in a temporary decrease in immune cells, such as T-cells and natural killer cells, but these levels returned to normal or increased within 24 to 48 hours, indicating a transient immunologic effect without promoting growth in leukemic cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of interleukin-2 in children with cancer and evaluation of clinical and immunologic status during therapy. A Pediatric Oncology Group Study. Nasr, S., McKolanis, J., Pais, R., et al.[2019]

Treatment with enteral nutrition or cyclosporin significantly reduced the percentage of IL-2 secreting cells in the intestinal mucosa of children with Crohn's disease after 8 weeks, indicating a potential mechanism for their therapeutic effects.

Enteral nutrition not only reduced lymphokine-secreting cells similarly to cyclosporin but also resulted in the best overall histological and clinical improvement, suggesting it may be a highly effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of treatment on lymphokine-secreting cells in the intestinal mucosa of children with Crohn's disease. Breese, EJ., Michie, CA., Nicholls, SW., et al.[2019]

Low-dose interleukin-2 (IL-2) significantly improved symptoms of ulcerative colitis in mice, reducing inflammation and restoring intestinal barrier integrity, indicating its potential as a treatment for this chronic condition.

The study identified that the therapeutic effects of low-dose IL-2 are mediated through the PI3K-AKT pathway, highlighting a specific mechanism of action that could be targeted in future treatments for ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose interleukin-2 alleviates dextran sodium sulfate-induced colitis in mice by recovering intestinal integrity and inhibiting AKT-dependent pathways. Lee, H., Son, YS., Lee, MO., et al.[2021]

BAY 50-4798, a novel IL-2 analog, shows similar potency to aldesleukin in stimulating T cell proliferation but with significantly reduced inflammatory responses, indicating a potentially safer profile for patients.

In studies comparing cytokine responses, BAY 50-4798 induced about 5-fold lower levels of endogenous IL-2 and at least 50% lower levels of proinflammatory cytokines compared to aldesleukin, suggesting it may have fewer side effects in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced secondary cytokine induction by BAY 50-4798, a high-affinity receptor-specific interleukin-2 analog. Steppan, S., Eckart, MR., Bajsarowicz, K., et al.[2013]

In a study involving 42 cancer patients treated with interleukin-2 (IL-2), serious gastrointestinal complications occurred in 3 patients, including life-threatening conditions like sigmoid colon perforation and ischemic necrosis.

Despite the common expectation of only minor side effects, the findings suggest that major gastrointestinal issues with IL-2 therapy may be more frequent than previously thought, highlighting the need for increased awareness and monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unusual gastrointestinal complications of interleukin-2 therapy. Rahman, R., Bernstein, Z., Vaickus, L., et al.[2019]

In patients with Crohn's disease and ulcerative colitis, interleukin 2 levels in cultured intestinal mucosa mononuclear cells were significantly lower compared to those from healthy tissues, indicating a potential deficiency in this important immune signaling molecule.

This deficiency in interleukin 2 may contribute to abnormal T-cell proliferation and a defective immune response, which could lead to the chronic inflammation observed in inflammatory bowel diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin 2 activity of human intestinal mucosa mononuclear cells. Decreased levels in inflammatory bowel disease. Fiocchi, C., Hilfiker, ML., Youngman, KR., et al.[2013]

High-dose interleukin-2 (IL-2) treatment in 500 patients with metastatic renal cell carcinoma (RCC) and melanoma showed an objective response rate of 28% for melanoma and 24% for RCC, indicating its efficacy in these cancers.

The treatment was found to be safe, with less than 1% of patients experiencing fatal outcomes, and severe toxicities like hypotension were manageable, suggesting that IL-2 can be effectively administered even in community hospitals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durable responses and reversible toxicity of high-dose interleukin-2 treatment of melanoma and renal cancer in a Community Hospital Biotherapy Program. Payne, R., Glenn, L., Hoen, H., et al.[2021]

Recombinant interleukin-2 is an effective immunomodulating agent that has shown promising results in treating renal cell carcinoma and melanoma, particularly in patients who do not respond well to conventional therapies.

While it can lead to significant adverse effects like hypotension and renal dysfunction, these effects are generally reversible, and its administration requires careful monitoring in a critical-care setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant interleukin-2: a biological response modifier. Kintzel, PE., Calis, KA.[2007]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04263831

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

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10523991/

Low-dose IL-2 for the Treatment of Moderate to Severe ... Among all subjects across all doses who completed the 8-week induction, 52.6% (10/19) achieved clinical response, with 21.1% (4/19) achieving clinical remission ...

3. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/392458

Low Dose IL-2 for the Treatment of Crohn's Disease Brief summary. The purpose of this study is to determine the safety and maximum effective dose (MED) of Interleukin-2 in subjects with moderate- ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12576968/

Efficacy of Advanced Therapies in Achieving Remission by ... The primary efficacy outcome was achieving clinical remission (defined as CDAI [Crohn's disease activity index] score <150), primarily assessed at end of ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02200445

NCT02200445 | Low Dose IL-2 for Ulcerative Colitis 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.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2012/103293s5130lbl.pdf

Proleukin (aldesleukin) injection label - accessdata.fda.gov The following data on life-threatening adverse events (reported in greater than 1% of patients, grade 4), presented by body system, and by preferred term ( ...

7. mountsinai.org mountsinai.org/clinical-trials/low-dose-il-2-for-treatment-of-crohns-disease

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

8. answers.childrenshospital.org answers.childrenshospital.org/ulcerative-colitis-il-2/

A promising option for unremitting ulcerative colitis New versions of IL-2 are becoming available that may be even more effective, he says. “Because of the good safety data, I think there's promise ...