Efficacy and Safety of AbGn-168H in Patients With Moderate to Severe Active, Anti-TNF Alpha and/or Anti-integrin Refractory Ulcerative Colitis

• ClinicalTrials.gov Identifier: NCT03298022
• Recruitment Status: Completed
• First Posted: September 29, 2017
• Last Update Posted: August 17, 2020
• Sponsor: AltruBio Inc.
• Information provided by (Responsible Party): AltruBio Inc.

Study Description

Brief Summary:

To evaluate the efficacy and safety of Neihulizumab (AbGn-168H) administered intravenously in patients with moderate to severe active ulcerative colitis who are refractory or intolerant to anti-Tumor Necrosis Factor α and/or anti-integrin treatments.

Condition or disease	Intervention/treatment	Phase
Ulcerative Colitis	Biological: AbGn-168H	Phase 2

Detailed Description:

This is a Phase II, open label, single arm, multiple dose proof of principle study to test the efficacy and safety of Neihulizumab in patients with moderate to severe active ulcerative colitis and who has failed or are intolerant to anti-TNFα and/or anti-integrin therapy. A minimum of 30 patients and a maximum of 40 will be recruited in 1 dosing group. For efficacy evaluation, the primary endpoint is the proportion of patients with clinical response, defined as ≥ 3- point reduction in MCS, 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 at Week 12. Safety assessments will consist of evaluating physical examination, vital signs (blood pressure, heart rate, respiratory rate, body temperature and oxygen saturation), safety laboratory tests, adverse events and tolerability.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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

Arms and Interventions

Arm	Intervention/treatment
Experimental: AbGn-168H; intravenous doses of AbGn-168H	Biological: AbGn-168H; monoclonal antibody; Other Name: Neihulizumab

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

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
2. 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
3. The proportion of responders who remain in clinical response and remission [ Time Frame: at 16-, 20- and 26-week after the first treatment ]
4. Flexible sigmoidoscopy subscore changes from baseline [ Time Frame: at 12- and 26-week after the first treatment ]
5. 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
6. 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
7. Change of histological activity grade from baseline using the Geboes system [ Time Frame: at 12- and 26-week after the first treatment ]
8. 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
9. Change of Inflammatory Bowel Disease Questionnaire from baseline [ Time Frame: at 12- and 26-week after the first treatment ]
10. 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
11. Faecal calprotectin changes [ Time Frame: at 4-, 9-, 12-, 16-, 20- and 26-week after the first treatment ]
12. C-reactive protein changes [ Time Frame: at 4-, 9-, 12-, 16-, 20- and 26-week after the first treatment ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patients must provide written informed consent;
2. Age 18-75 years;
3. 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);

4. Moderate-to-severe active UC, at time of screening, defined as:

   1. Mayo Clinic Score (MCS) of 6 points or higher, AND
   2. a centrally read MCS endoscopic subscore of grade 2 or higher, AND
   3. MCS rectal bleeding subscore of 1 point or higher, AND
   4. disease extending 15 cm or more from the anal verge;

5. Stable doses of concomitant medications, including :

   1. 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;
   2. Stable oral 5-aminosalicylic acid dose ≥ 2 weeks before D1 dosing;
   3. 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;
   4. Stable doses of probiotics ≥ 2 weeks before D1 dosing;
   5. Stable anti-diarrheas ≥ 2 weeks before D1 dosing;
6. 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;
7. Patients previously treated with cyclosporine or tacrolimus must have discontinued therapy ≥ 4 weeks before D1 dosing;
8. Topical corticosteroids and topical 5-amyinosalicylic acid preparations must have been withdrawn ≥ 2 weeks before D1 dosing;
9. Nonsteroidal anti-inflammatory drugs (NSAIDs) must have been discontinued ≥ 4 weeks before D1 dosing;
10. Tofacitinib or other Janus kinase (JAK) inhibitors must have been discontinued ≥ 2 weeks before D1 dosing;
11. Patients previously treated with tube feeding, defined formula diets, or parenteral alimentation/nutrition must have discontinued treatment 3 weeks before D1 dosing;
12. 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).

Exclusion Criteria:

- GI related exclusion criteria:

1. Indeterminate colitis (IBD-U) or suspected Crohn's disease
2. Any history of colectomy
3. Presence of an ileostomy or colostomy
4. A history or evidence of colonic mucosal dysplasia

5. Short gut syndrome

   -General health related exclusion criteria:

6. Pregnant or lactating
7. Inability to comply with study protocol in the opinion of the investigator
8. 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
9. Cirrhosis or active alcohol abuse per the judgement of investigator
10. Poorly controlled diabetes (HbA1c > 8.0%)
11. Significant screening ECG abnormalities, including evidence of acute myocardial infarction, complete left bundle branch block, second-degree heart block, or complete heart block
12. Impaired renal function (calculated creatinine clearance < 60 mL/min)
13. 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
14. Moderate to severe anemia (Hb < 8g/dL)
15. Thrombocytopenia (platelet count < 75,000/uL)
16. 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
17. Requiring parenteral corticosteroid treatment.
18. Received any investigational product within 1 year.

19. 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:

20. Human immune deficiency virus (HIV) infection or known HIV-related malignancy.
21. 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.
22. Positive IgM antibody titers in the presence of negative IgG titers to Epstein-Barr virus
23. 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.
24. Intestinal mucosa biopsy positive for cytomegalovirus (CMV) at screening.
25. 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.
26. History of any opportunistic infection ≤ 12 weeks before D1 dosing.
27. Any current or recent (≤ 4 weeks before D1 dosing) symptoms/signs of infection.
28. Received oral antibiotics ≤ 4 weeks before D1 dosing or intravenous antibiotics ≤ 8 weeks before D1 dosing.
29. Received a live attenuated vaccine ≤ 4 weeks before D1 dosing.
30. Neutropenia (absolute neutrophil count < 1,500/uL).
31. Lymphocytopenia (absolute lymphocyte count < 500 /uL).

Contacts and Locations

Locations

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

Capitol Research

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

Puerto Rico

Wellness Clinical Research (WCR)

Vega Baja, Puerto Rico, 00694

Sponsors and Collaborators

AltruBio Inc.

Investigators

• Study Director: Shih-Yao Lin, MD, PhD; AltruBio Inc.
• Principal Investigator: David T Rubin, MD; University of Chicago

More Information

• Responsible Party: AltruBio Inc.
• ClinicalTrials.gov Identifier: NCT03298022
• Other Study ID Numbers: 2017.008.01
• First Posted: September 29, 2017
• 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

Keywords provided by AltruBio Inc.:

Ulcerative Colitis

Additional relevant MeSH terms:

Colitis; Colitis, Ulcerative; Ulcer; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Pathologic Processes; Inflammatory Bowel Diseases