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Evaluation of Safety, Efficacy, Pharmacokinetic and Pharmacodynamic of Bertilimumab in Patients With Active Moderate to Severe Ulcerative Colitis

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2014 by Immune Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Immune Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01671956
First received: August 9, 2012
Last updated: July 27, 2014
Last verified: July 2014
  Purpose

This is a randomized, double blind, placebo-controlled, parallel group multi-center study in adult patients with active moderate to severe UC . Eligible patients will be randomly assigned in a 2:1 ratio to one of two treatment groups, bertilimumab 10 mg/kg or matching placebo, respectively


Condition Intervention Phase
Ulcerative Colitis, Active Moderate
Ulcerative Colitis, Active Severe
Biological: Bertilimumab
Biological: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multi-Center Study Designed to Evaluate the Safety, Efficacy, Pharmacokinetic and Pharmacodynamic Profile of Bertilimumab in Patients With Active Moderate to Severe Ulcerative Colitis

Resource links provided by NLM:


Further study details as provided by Immune Pharmaceuticals:

Primary Outcome Measures:
  • Clinical response [ Time Frame: Day 56 ] [ Designated as safety issue: No ]
    • A decrease in Mayo score from baseline of at least 3 points and at least 30% AND
    • Either a decrease in the sub-score for rectal bleeding of at least 1 point, or rectal bleeding sub-score of 0 or 1.


Secondary Outcome Measures:
  • Change in UCEIS score from screening to Day 56 [ Time Frame: Da 56 ] [ Designated as safety issue: No ]
  • Clinical remission at Day 56, defined as a total Mayo score of 2 points or lower, with no individual sub-score exceeding 1 point [ Time Frame: Day 56 ] [ Designated as safety issue: No ]
  • Mucosal healing at Day 56, defined as an absolute sub-score for endoscopy of 0 or 1. [ Time Frame: Day 56 ] [ Designated as safety issue: No ]
  • Change in partial Mayo score from Day 0 to all scheduled measurement timepoints (efficacy follow up). [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • PHARMACOKINETICS [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]
    PK analysis for bertilimumab concentration: blood samples will be collected on dosing days (pre-dose and at 30 minutes and 4 hours following initiation of study drug infusion) and at the follow-up visits. The following PK parameters will be calculated, to the degree possible given the number of timepoints: Cmax, Tmax, Cavg, Cmin and t1/2. Additional standard and exploratory PK parameters will be calculated if deemed necessary

  • PHARMACODYNAMIC [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]
    • Fecal calprotectin change from Day 0 (baseline) to all scheduled measurement timepoints.
    • PD analysis of eosinophil shape change: blood samples will be collected on dosing days (pre-dose and on Day 0 only, at 4 hours following initiation of study drug infusion), and at the follow-up visits.
    • Change in eosinophil count, serum eotaxin-1 and hs-CRP from Day 0 to all scheduled measurement timepoints.
    • Change in eotaxin-1 concentration and eosinophil count in biopsy tissue from Screening to Day 56

  • Safety [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
    • Adverse events (AE)
    • Injection site reactions
    • Physical examination
    • Vital signs (blood pressure, heart rate, temperature and respiratory rate)
    • ECG
    • Concomitant medications
    • Laboratory evaluation (hematology, biochemistry, anti-bertilimumab antibodies).


Estimated Enrollment: 42
Study Start Date: August 2014
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bertilimumab
Bertilimumab 10 mg/kg will be administered by IV infusion over 30 minutes
Biological: Bertilimumab
Placebo Comparator: Placebo
Phosphate buffered saline (PBS) placebo will be administered by IV infusion over 30 minutes.
Biological: Placebo

Detailed Description:

This is a randomized, double blind, placebo-controlled, parallel group multi-center study in adult patients with active moderate to severe UC . Eligible patients will be randomly assigned in a 2:1 ratio to one of two treatment groups, bertilimumab 10 mg/kg or matching placebo, respectively.

The study will consist of three periods: a screening period of up to two weeks, a 4-week double-blind treatment period (three IV infusions at 2-week intervals), and a safety and efficacy follow-up period of approximately 9 weeks.

Bertilimumab is a recombinant human IgG4 monoclonal antibody that neutralizes human eotaxin-1 (eotaxin). Bertilimumab will be administered every other week for 4-weeks, by IV infusion over 30 minutes.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males or females, 18 to 70 years of age inclusive.
  2. Diagnosed with active moderate to severe UC per standard diagnostic criteria for a minimum of 3 months:

    • Mayo score of 6-12 (inclusive) at the Screening Visit
    • Endoscopic evidence of active mucosal disease, as assessed by flexible sigmoidoscopy, with an Endoscopic Finding Sub-score of ≥2 (assessed centrally)
    • Rectal Bleeding Sub-score of ≥1
    • Physician's Global Assessment (PGA) Sub-score of ≥2.
  3. Levels of eotaxin-1 in biopsied colon tissue of ≥100 pg/mg protein.
  4. Adequate cardiac, renal and hepatic function as determined by the Investigator and demonstrated by screening laboratory evaluations and physical examination results; these findings must all be within normal limits or judged not clinically significant by the Investigator.

Exclusion Criteria:

  1. History of colonic or rectal surgery other than hemorrhoidal surgery or appendectomy.
  2. Currently receiving total parenteral nutrition (TPN).
  3. Positive Clostridium difficile toxin stool assay.
  4. Tested positive for active/latent mycobacterium tuberculosis (TB) infection.
  5. Pregnant or breast-feeding, or plan to become pregnant during the study.
  6. Males who are young and childless or planning to have more children in the future.
  7. Known hypersensitivity to bertilimumab or any of the drug excipients.
  8. History of infection requiring administration of any IV antibiotic, antiviral or antifungal medication within 30 days of Screening or any oral anti-infective agent within 14 days of Screening.
  9. Severe UC evidenced by the following signs of toxicity: heart rate >100 beats/min at rest, temperature >37.8°C, hemoglobin <10.0 g/dL.
  10. Ulcerative proctitis, defined as disease limited to less than 15 cm from the anal verge.
  11. Received a vaccine or other immunostimulator within 4 weeks prior to screening.
  12. Use of >4.8 g mesalazine or equivalent within 2 weeks prior to the screening visit. Mesalazine ≤4.8 g is allowed if the dose during the 2 weeks prior to the screening visit was stable.
  13. Use of systemic corticosteroids exceeding the equivalent of 20 mg/day of prednisone within four weeks prior to the screening visit (see Section 6.9.1).
  14. Change in dose of immunosuppressive drugs (e.g., corticosteroids, 6-mercaptopurine [6-MP], azathioprine) within four weeks prior to the screening visit.
  15. Use of TNF-blockers (e.g., infliximab or adalimumab) within 60 days of the screening visit.
  16. Use of chronic non-steroidal anti-inflammatory (NSAID) therapy. Occasional use of NSAIDs or acetaminophen for headache, arthritis, myalgias, menstrual cramps, etc., or daily use of low dose (81-162 mg) aspirin for cardiovascular prophylaxis is allowed.
  17. Patients diagnosed with:

    • Crohn's disease
    • Diverticulitis or diverticulosis
    • Indeterminate colitis (inability to distinguish between UC and Crohn's disease [as assessed by the Investigator])
    • Microscopic colitis (collagenous or lymphocytic colitis)
    • Ischemic or infectious colitis
    • Clostridium difficile colitis within 90 days of the screening visit
    • Parasitic disease within 90 days of the screening visit
    • Systemic fungal infection within 90 days of the screening visit.
  18. History of positive serology of hepatitis B or C, or human immunodeficiency virus (HIV) infection.
  19. Congenital or acquired immunodeficiency (e.g., common variable immunodeficiency, organ transplantation).
  20. Clinically significant abnormal laboratory test results, unless regarded by the Investigator as related to UC, including but not limited to:

    • Hemoglobin level <10.0 g/dL
    • White blood cell count < 3 x 103/µL
    • Lymphocyte count < 0.5 x 103/µL
    • Platelet count <100 x 103/µL or >1200 x 103/µL
    • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 the upper limit of normal (ULN)
    • Alkaline phosphatase >3 ULN
    • Serum creatinine >2 ULN.
  21. Active abuse of alcohol or drugs.
  22. Known malignancy or history of malignancy that could reduce life expectancy.
  23. Any condition, which in the opinion of the Investigator, would place the patient at an unacceptable risk if participating in the study protocol.
  24. Participation in a clinical trial of an investigational (unapproved) product
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01671956

Locations
Israel
Rambam Medical Center Not yet recruiting
Haifa, Israel, 31096
Contact: Mati Waterman    972-50-2061361    m_waterman@rambam.health.gov.il   
Contact: Daliya Katz, Study Cordinator    972-4-8541777    dl_katz@rambam.health.gov.il   
Principal Investigator: Mati Waterman, Dr         
Wolfson Medical Center Not yet recruiting
Holon, Israel, 58100
Contact: Yona Avni, Dr    972-3-5028499    avni@wolfson.health.gov.il   
Contact: Orit Shevah, Study Cordunator    972-50-2562560    oritsh@wolfson.health.gov.il   
Principal Investigator: Yona Avni, Dr         
Hadassah Ein Kerem Not yet recruiting
Jerusalem, Israel, 91120
Contact: Eran Israeli, Dr    972-2-6776848    erani@hadassah.org.il   
Contact: Galina Gerber, Study Cordinator    972-50-5172626    galinag@hadassah.org.il   
Principal Investigator: Eran Israeli, Dr         
Shaare Tzedek Medical Central Not yet recruiting
Jerusalem, Israel, 91031
Contact: Eran Goldin, Prof.    02-6555916    erang@szmc.org.il   
Contact: Chava Kaniel, Study Cordinator    972-2-6666916    chavak@szmc.org.il   
Principal Investigator: Eran Goldin, Prof         
Meir Medical Center Not yet recruiting
Kfar-Saba, Israel, 44299
Contact: Fred Konikoff, Prof    972-09-7472523    Fred.Konikoff@clalit.org.il   
Contact: Lee Graidy, Study Cordinator    972-9-7471017    lee.graidy@clalit.org.il   
Principal Investigator: Fred Kinikoff, Prof         
Sourasky-Ichilov Tel Aviv Medical Center Not yet recruiting
Tel- Aviv, Israel, 64239
Contact: Sigal Fishman, Dr    972-52-4262625    sigalf@tlvmc.gov.il   
Contact: Liana Shmialov, Study Cordinator    972-52-6608388    lianash@tlvmc.gov.il   
Principal Investigator: Sigal Fishman, Dr         
Sponsors and Collaborators
Immune Pharmaceuticals
Investigators
Principal Investigator: Eran Goldin, Prof Shaare Zedek Medical Center
  More Information

No publications provided

Responsible Party: Immune Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01671956     History of Changes
Other Study ID Numbers: Immune/BRT/UC-01
Study First Received: August 9, 2012
Last Updated: July 27, 2014
Health Authority: Israel: Ministry of Health

Keywords provided by Immune Pharmaceuticals:
IBD
UC
Colitis
Ulcerative Colitis

Additional relevant MeSH terms:
Colitis
Colitis, Ulcerative
Ulcer
Colonic Diseases
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Inflammatory Bowel Diseases
Intestinal Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on November 24, 2014