Clinical trial NCT01671956: Evaluation of Safety, Efficacy, Pharmacokinetic and Pharmacodynamic of Bertilimumab in Patients With Active Moderate to Severe Ulcerative Colitis
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Ulcerative Colitis, Active Moderate
Ulcerative Colitis, Active Severe
Keywords: IBD
UC
Colitis
Ulcerative Colitis
Lead sponsor: Immune Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2012-08-24
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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 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

Primary outcomes:
measure: Clinical response
timeFrame: Day 56
Secondary outcomes:
measure: Change in UCEIS score from screening to Day 56
timeFrame: Da 56
measure: Clinical remission at Day 56, defined as a total Mayo score of 2 points or lower, with no individual sub-score exceeding 1 point
timeFrame: Day 56
measure: Mucosal healing at Day 56, defined as an absolute sub-score for endoscopy of 0 or 1.
timeFrame: Day 56
measure: Change in partial Mayo score from Day 0 to all scheduled measurement timepoints (efficacy follow up).
timeFrame: Throughout the study
Other outcomes:
measure: PHARMACOKINETICS
timeFrame: Throughout the study
measure: PHARMACODYNAMIC
timeFrame: Throughout the study
measure: Safety
timeFrame: Throughout the study
Locations:
city: Afula
country: Israel
facility: HaEmek Medical Center
city: Holon
country: Israel
facility: Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Central
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem
city: Kfar-Saba
country: Israel
facility: Meir Medical Center
city: Tel- Aviv
country: Israel
facility: Sourasky-Ichilov Tel Aviv Medical Center
Study officials:
affiliation: Shaare Zedek Medical Center, Jerusalem, Israel
name: Dov Wengrower, MD
role: PRINCIPAL_INVESTIGATOR
References: