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Ulcerative ColitisPhase 1NCT02200445

Low Dose IL-2 for Ulcerative Colitis

A Phase 1 study testing Interleukin-2 (aldesleukin). in people with Ulcerative Colitis, run by Scott B. Snapper, MD PHD at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Ulcerative Colitis
What is being tested?
Interleukin-2 (aldesleukin).
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
2 sitesUnited States
Study dates
Feb 2015to Mar 2021
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 21Show fewer
  • Significant laboratory abnormalities, including;
  • Hb < 8.0 g/dL, WBC < 2.5 x 103/mm3, Plt < 100 x 103/mm3.
  • Creatinine ≥ 1.5x institutional upper limit of normal (ULN).
  • Total bilirubin > 2.0 mg/dL, ALT > 2x institutional ULN, GGT > 2x institutional ULN. Elevated unconjugated bilirubin related to Gilbert's syndrome is allowed.
  • 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).

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

  • Brigham & Women's Hospital

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: A Phase I Study of Low Dose Subcutaneous Interleukin-2 (IL-2) For The Treatment of 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.

Read the detailed description

Interleukin-2 (IL-2) is a T cell growth factor. IL-2 is currently licensed for the treatment of metastatic renal cell carcinoma and metastatic melanoma, where it promotes the expansion of anti-cancer cytotoxic T cells and natural killer (NK) cells. However at low doses (100-times lower than those used in cancer therapy), IL-2 promotes the selective expansion of regulatory T cells (Tregs): an immune modulating subset of CD4+ lymphocytes.

A recent phase 1 clinical trial from our collaborators at the Dana Farber Cancer Institute showed that low-dose IL-2 selectively expands Tregs in patients with treatment-resistant Graft vs. Host Disease (GvHD), and that low-dose IL-2 is safe in this condition. A detailed immunological analysis of samples from this study showed that low-dose IL-2 treatment was associated with increased Treg proliferation, increased de novo thymic generation of Tregs, and a resolution of defects in intracellular signalling and apoptosis seen in Tregs in chronic GvHD. A recent phase 1 study from another group showed that low-dose IL-2 is safe in the treatment of HCV-associated vasculitis. Low-dose IL-2 has also been shown to be well-tolerated in subjects with HIV.

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Evidence from pre-clinical models of intestinal inflammation, and also from patients with monogenetic defects in Treg function, suggests that Tregs play a role in the prevention of inflammation in the intestine.

The treatment (or intervention) in this study is a once-daily, subcutaneous injection of IL-2, for a total of 8 weeks. The first 2 doses of the study drug will be administered by research nurses at Boston Children's Hospital. Further doses will be self-administered, at home. Training will be provided for correct self-administration.

This is a 3+3 dose escalation study of IL-2 in moderate-to-severe UC. This study design is powered to identify the MED of low-dose IL-2 in UC. Once the MED is identified, a further 10 subjects will receive IL-2 at that dose. Recruitment of between 2 and 28 patients is planned. The maximum tolerated dose (MED) is the highest tolerated dose level at which a minimum of 6 subjects have been evaluated, with fewer than 2 evaluable subjects in 6 experiencing a dose limiting toxicity (DLT); i.e. DLT in >1/6 evaluable subjects. In addition to the above at least 1 patient should meet the criteria for response or remission for it to be considered the MED.

Dose levels are based on the experience of our collaborators in GvHD. In addition to determining the MED, this study will determine if low-dose IL-2 is safe and well-tolerated in patients with moderate-to-severe ulcerative colitis. A detailed immunological analysis of samples obtained from this study will determine if low-dose IL-2 expands Tregs in vivo, in patients with moderate-to-severe UC. Immunological changes will then be correlated with clinical response.

The study will take place at Boston Children's Hospital. The study will involve 10 study visits. Most of the study visits involve blood tests. A flexible sigmoidoscopy or colonoscopy will be performed as part of the screening process. A flexible sigmoidoscopy will also be performed on completion of therapy, to determine clinical response.

The first two subjects to receive the study drug will be admitted overnight following the first dose. Subsequent doses will be administered on an out-patient basis. All other subjects will receive IL-2 on an out-patient basis.

Responders (with an acceptable side-effect profile) will be allowed to continue the study drug for at least 1 year. Compensation will be provided for participants.

Being tested
Interleukin-2 (aldesleukin).
Keywords
Ulcerative colitis, Inflammatory bowel disease, Interleukin 2, Interleukin-2, IL-2, Regulatory T Cells, Tregs, T-Lymphocytes, Regulatory
Medical subject headings
Colitis, Ulcerative, Inflammatory Bowel Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Interleukin-2 (aldesleukin).Drug

    Also called Proleukin.

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

Study groups in NCT02200445
Study groupRoleWhat they receive
Interleukin-2ExperimentalStudy 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 three 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: 0.3x10^6 IU/m^2/day. * Cohort 2: 1.0x10^6 IU/m^2/day. * Cohort 3: 1.5x10^6 IU/m^2/day. Up to 6 subjects will be recruited to each dose cohort. Once the maximum effective dose has been identified, a further 10 subjects will receive IL-2 at the maximum effective dose.
Receives: Drug: Interleukin-2 (aldesleukin).

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Subjects With Serious and Non-serious Adverse Events.

    Enumeration of the serious and non-serious adverse events seen in the study. Enumeration of any dose limiting toxicity seen in the study.

    Measured: 8 weeks

Secondary outcomes (2)

  1. Number of Participants With Clinical Response

    A decrease from baseline in the total Mayo score of at least 3 points and at least 30% , with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1

    Measured: 8 weeks.

  2. Number of Participants With Clinical Remission

    A total Mayo score of 2 points or lower, with no individual subscore exceeding 1 point

    Measured: 8 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jul 2014 (estimated)
  2. Study startFeb 2015
  3. Primary completion1 Oct 2020
  4. Study completionMar 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02200445
Sponsor's protocol ID
IRB-P00009599
Other IDs
2015P000016
Status last verified
Aug 2022
First submitted
22 Jul 2014
Last updated
15 Jun 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 22129252

  • 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.

    PubMed 23552371

  • 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.

    PubMed 22129253

  • 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.

    PubMed 3317057

  • 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.

    PubMed 16339095

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Interleukin-2 (aldesleukin). in people with Ulcerative Colitis, run by Scott B. Snapper, MD PHD at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With Serious and Non-serious Adverse Events. (time frame: 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02200445, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2023.

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Low Dose IL-2 for Ulcerative Colitis (NCT02200445) | AzTrials