Efficacy and Safety of AbGn-168H in Patients With Moderate to Severe Active, Anti-TNF Alpha and/or Anti-integrin Refractory Ulcerative Colitis
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|ClinicalTrials.gov Identifier: NCT03298022|
Recruitment Status : Completed
First Posted : September 29, 2017
Last Update Posted : August 17, 2020
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|Condition or disease||Intervention/treatment||Phase|
|Ulcerative Colitis||Biological: AbGn-168H||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Efficacy and Safety of AbGn-168H in Patients With Moderate to Severe Active, Anti-TNF Alpha and/or Anti-integrin Refractory Ulcerative Colitis: a 26-week, Open-label, Multi-center, Phase II Proof of Principle Trial|
|Actual Study Start Date :||April 10, 2018|
|Actual Primary Completion Date :||April 6, 2020|
|Actual Study Completion Date :||June 1, 2020|
intravenous doses of AbGn-168H
Other Name: Neihulizumab
- The proportion of patients with clinical response at Week 12 [ Time Frame: at 12-week after the first treatment ]The clinical response is defined as a ≥ 3-point reduction in Mayo Clinical Score, a 30% or greater decrease from the baseline score, and with a 1-point or greater decrease of the rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1
- The proportion of patients with clinical response [ Time Frame: at 6-, 7-, 9- and 11-week after the first treatment ]The clinical response is defined as a ≥2-point decrease in partial Mayo Clinical Score, and with a 1-point or greater decrease of the rectal bleeding subscore or an absolute rectal bleeding score of 0 or 1
- The proportion of patients with clinical remission [ Time Frame: at 6-, 7-, 9-, 11- and 12-week after the first treatment ]The clinical remission is defined as Mayo Clinical Score of 2 or lower (or partial Mayo Clinical Score of 1 or lower) and no subscore higher than 1
- The proportion of responders who remain in clinical response and remission [ Time Frame: at 16-, 20- and 26-week after the first treatment ]
- Flexible sigmoidoscopy subscore changes from baseline [ Time Frame: at 12- and 26-week after the first treatment ]
- The proportion of patients with sigmoidoscopic improvement [ Time Frame: at 12- and 26-week after the first treatment ]The endoscopic improvement is defined as any decrease in Mayo Clinical Score endoscopic subscore
- The proportion of patients with mucosa healing [ Time Frame: at 12- and 26-week after the first treatment ]The mucosa healing is defined as an absolute subscore for endoscopy of 0 or 1
- Change of histological activity grade from baseline using the Geboes system [ Time Frame: at 12- and 26-week after the first treatment ]
- The proportion of patients with histological healing [ Time Frame: at 12- and 26-week after the first treatment ]The histological healing is defined as histological grade = 0
- Change of Inflammatory Bowel Disease Questionnaire from baseline [ Time Frame: at 12- and 26-week after the first treatment ]
- The proportion of patients with Inflammatory Bowel Disease Questionnaire (IBDQ) response [ Time Frame: at 12- and 26-week after the first treatment ]The IBDQ response is defined as an increase from baseline of at least 16 points
- Faecal calprotectin changes [ Time Frame: at 4-, 9-, 12-, 16-, 20- and 26-week after the first treatment ]
- C-reactive protein changes [ Time Frame: at 4-, 9-, 12-, 16-, 20- and 26-week after the first treatment ]
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|Ages Eligible for Study:||18 Years to 75 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Patients must provide written informed consent;
- Age 18-75 years;
- Diagnosis of UC ≥ 12 weeks prior to screening by full colonoscopy (i.e., ≥ 12 weeks after first diagnosis by a physician according to American College of Gastroenterology guidelines);
Moderate-to-severe active UC, at time of screening, defined as:
- Mayo Clinic Score (MCS) of 6 points or higher, AND
- a centrally read MCS endoscopic subscore of grade 2 or higher, AND
- MCS rectal bleeding subscore of 1 point or higher, AND
- disease extending 15 cm or more from the anal verge;
Stable doses of concomitant medications, including :
- Stable oral corticosteroids (i.e., ≤ 20 mg/day of prednisone, ≤ 9 mg/day of budesonide) ≥ 2 weeks before D1 dosing; Taper of oral corticosteroids per Investigator's discretion during the study is allowed;
- Stable oral 5-aminosalicylic acid dose ≥ 2 weeks before D1 dosing;
- Stable immunosuppressant including azathioprine, mercaptopurine, or methotrexate ≥ 8 weeks before D1 dosing. Patients taking methotrexate also are advised to take folic acid 1 mg/day or equivalent if there is no contraindication;
- Stable doses of probiotics ≥ 2 weeks before D1 dosing;
- Stable anti-diarrheas ≥ 2 weeks before D1 dosing;
- Patients must have previously received anti-tumor necrosis factor alpha (anti-TNF alpha and/or anti-integrin therapy for UC and demonstrated an inadequate response, loss of response, or intolerance, and must have discontinued therapy ≥ 8 weeks before D1 dosing;
- Patients previously treated with cyclosporine or tacrolimus must have discontinued therapy ≥ 4 weeks before D1 dosing;
- Topical corticosteroids and topical 5-amyinosalicylic acid preparations must have been withdrawn ≥ 2 weeks before D1 dosing;
- Nonsteroidal anti-inflammatory drugs (NSAIDs) must have been discontinued ≥ 4 weeks before D1 dosing;
- Tofacitinib or other Janus kinase (JAK) inhibitors must have been discontinued ≥ 2 weeks before D1 dosing;
- Patients previously treated with tube feeding, defined formula diets, or parenteral alimentation/nutrition must have discontinued treatment 3 weeks before D1 dosing;
- Females with reproductive potential must have a negative pregnancy test result before enrollment. Men and women with reproductive potential have to be willing to use a highly effective method of contraception from study start to ≥ 3 months after the final dose of the study drug. A highly effective method of birth control is defined as one which results in a low failure rate (less than 1% per year).
- GI related exclusion criteria:
- Indeterminate colitis (IBD-U) or suspected Crohn's disease
- Any history of colectomy
- Presence of an ileostomy or colostomy
- A history or evidence of colonic mucosal dysplasia
Short gut syndrome
-General health related exclusion criteria:
- Pregnant or lactating
- Inability to comply with study protocol in the opinion of the investigator
- History of dysplasia or malignancy in recent 5 years, except completely excised basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
- Cirrhosis or active alcohol abuse per the judgement of investigator
- Poorly controlled diabetes (HbA1c > 8.0%)
- Significant screening ECG abnormalities, including evidence of acute myocardial infarction, complete left bundle branch block, second-degree heart block, or complete heart block
- Impaired renal function (calculated creatinine clearance < 60 mL/min)
- Impaired hepatic function in the absence of diagnosis of primary sclerosing cholangitis, serum transaminase > 2.5x Upper Limit Normal (ULN), alkaline phosphatase > 2.5x ULN, or increased total bilirubin judged by the investigator to be clinically significant, or a diagnosis of primary sclerosing cholangitis, serum transaminases > 3x ULN, alkaline phosphatase > 3x ULN, or total bilirubin > 2.5x ULN judged by the investigator to be clinically significant
- Moderate to severe anemia (Hb < 8g/dL)
- Thrombocytopenia (platelet count < 75,000/uL)
- Evidence of current or previous clinically significant disease, medical condition or finding in the medical examination that in the opinion of the investigator, would compromise the safety of the patient or quality of the data
- Requiring parenteral corticosteroid treatment.
- Received any investigational product within 1 year.
History of drug abuse according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) criteria within 12 months prior to screening or positive drug screening tests.
-Infection related exclusion criteria:
- Human immune deficiency virus (HIV) infection or known HIV-related malignancy.
- Acute or chronic hepatitis B or C, or carrier status. Patients with anti-HBc Ab but with undetectable anti-HBs Ab should also be excluded.
- Positive IgM antibody titers in the presence of negative IgG titers to Epstein-Barr virus
- Positive stool test for ova or parasites, positive stool culture for pathogens, or positive stool toxin assay for Clostridium difficile at screening. Patients with the positive stool toxin assay for C. difficile at screening could be rescreened if they are being treated for C. difficile and a repeat stool toxin assay at least 4 weeks after the completion of treatment is negative with no evidence of recurrence.
- Intestinal mucosa biopsy positive for cytomegalovirus (CMV) at screening.
- Positive screening test for latent Mycobacterium tuberculosis (TB) infection. Patients with a history of latent TB infection who received an appropriate and documented course of therapy can be included if the screening examination and a chest x-ray performed ≤ 3 months before screening revealed no evidence of current active infection. If a Quantiferon TB test is indeterminate, the test should be repeated, and if the result is again indeterminate, such patient should be excluded.
- History of any opportunistic infection ≤ 12 weeks before D1 dosing.
- Any current or recent (≤ 4 weeks before D1 dosing) symptoms/signs of infection.
- Received oral antibiotics ≤ 4 weeks before D1 dosing or intravenous antibiotics ≤ 8 weeks before D1 dosing.
- Received a live attenuated vaccine ≤ 4 weeks before D1 dosing.
- Neutropenia (absolute neutrophil count < 1,500/uL).
- Lymphocytopenia (absolute lymphocyte count < 500 /uL).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03298022
|United States, Arkansas|
|Lynn Institute of the Ozarks|
|Little Rock, Arkansas, United States, 72205|
|United States, California|
|Stomach Doctor - Surinder Saini, MD - Fountain Valley|
|Newport Beach, California, United States, 92660|
|United States, Florida|
|Wellness Clinical Research (WCR)|
|Hialeah, Florida, United States, 33016-2202|
|Wellness Clinical Research (WCR)|
|Lake Wales, Florida, United States, 33853|
|United States, Illinois|
|Northwestern University Feinberg School of Medicine|
|Chicago, Illinois, United States, 60611|
|University of Chicago|
|Chicago, Illinois, United States, 60637|
|United States, Maryland|
|Rockville, Maryland, United States, 20850|
|United States, New York|
|Weill Cornell Medical College|
|New York, New York, United States, 10021|
|University of Rochester Medical Center|
|Rochester, New York, United States, 14642|
|United States, Texas|
|Baylor College of Medicine|
|Houston, Texas, United States, 77030|
|United States, Washington|
|University of Washington Medical Center (UWMC) - Digestive Disease Center|
|Seattle, Washington, United States, 98195|
|Wellness Clinical Research (WCR)|
|Vega Baja, Puerto Rico, 00694|
|Study Director:||Shih-Yao Lin, MD, PhD||AltruBio Inc.|
|Principal Investigator:||David T Rubin, MD||University of Chicago|
|Responsible Party:||AltruBio Inc.|
|Other Study ID Numbers:||
|First Posted:||September 29, 2017 Key Record Dates|
|Last Update Posted:||August 17, 2020|
|Last Verified:||August 2020|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Digestive System Diseases
Inflammatory Bowel Diseases