Low Dose IL-2 for Ulcerative Colitis

NCT02200445 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: IRB-P000095992015P000016
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Ulcerative Colitis

Keywords

Ulcerative colitis; Inflammatory bowel disease; Interleukin 2; Interleukin-2; IL-2; Regulatory T Cells; Tregs; T-Lymphocytes, Regulatory

Outcome Measures

Primary Outcomes (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.

  8 weeks

Secondary Outcomes (2)

• Number of Participants With Clinical Response

  8 weeks.

• Number of Participants With Clinical Remission

  8 Weeks

Study Arms (1)

Interleukin-2

EXPERIMENTAL

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 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.

Drug: Interleukin-2 (aldesleukin).

Interventions

Interleukin-2 (aldesleukin). DRUG

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

Also known as: Proleukin.

Interleukin-2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Scott B. Snapper, MD PHD: lead

Study Sites (2)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (5)

• 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.

  PMID: 22129252 BACKGROUND

• 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.

  PMID: 23552371 BACKGROUND

• 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.

  PMID: 22129253 BACKGROUND

• 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.

  PMID: 3317057 BACKGROUND

• 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.

  PMID: 16339095 BACKGROUND

MeSH Terms

Conditions

Colitis, Ulcerative; Inflammatory Bowel Diseases

Interventions

aldesleukin

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases

Results Point of Contact

• Title: Dr. Jessica Allegretti
• Organization: Brigham and Women's Hospital

jallegretti@bwh.harvard.edu

617-732-5500

Study Officials

• Scott B Snapper, MD PhD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

• Jessica R Allegretti, MD, MPH

  Brigham and Women's Hospital

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: July 22, 2014
• First Posted: July 25, 2014
• Study Start: February 1, 2015
• Primary Completion: October 1, 2020
• Study Completion: March 1, 2021
• Last Updated: June 15, 2023
• Results First Posted: December 19, 2020

Record last verified: 2022-08

Locations

US (2)