SAD/MAD Study in Healthy Subjects and Adults With UC to Evaluate Safety, Tolerability, PK, PD of AMT-101

Study Overview
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Brief Summary
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A randomized, double-blind placebo-controlled first in human study in approximately 36 male healthy subjects and approximately 20 male and female patients with active UC who have had an inadequate response to or demonstrated intolerance to 5-ASA.

Detailed Description
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A randomized, double-blind placebo-controlled first in human study in approximately 36 male healthy subjects and approximately 20 male and female patients with active UC who have had an inadequate response to or demonstrated intolerance to 5-ASA. Subjects may but are not required to have been exposed to corticosteroids, or immunosuppressive agents. In case the subject has been exposed to any of these treatments, he/she must have had either an inadequate response, failed response or demonstrated intolerance. Patients may be naïve to anti-TNFα therapy or have failed or demonstrated intolerance to anti-TNF-α therapy.

Official Title
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A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose in Healthy Subjects and Multiple-Ascending Dose in Adult Patients With Ulcerative Colitis Study to Evaluate the Safety, Tolerability, PK and PD of Oral AMT-101

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: AMT-101
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PART A (Healthy Volunteers) Male subject in good health as determined by past medical history, physical examination, vital signs, ECG, and laboratory tests at screening Between 18 and 45 years of age, inclusive. Body Mass Index (BMI) between 18 and 30 kg/m2 (inclusive). PART B (Adult Ulcerative Colitis) Male and Female patients 18 years and older Documented diagnosis of UC for at least 3 months duration Stable mild to moderate UC, as defined by the following criteria: Total Mayo score (excluding PGA) at least 3 but not greater than 7: Patients must have failed or demonstrated intolerance to aminosalicylates (e.g., 5-aminosalicylic acid, mesalamine) Exclusion Criteria: PART A and PART B Known hypersensitivity or allergy to AMT-101 or excipient contained in the drug formulation. Clinically significant abnormalities in laboratory test results (including complete blood count, chemistry panel including kidney panel, and urinalysis). PART B Clinical findings of Crohn's disease A prior history of surgery for UC Prior use of integrin antagonists (vedolizumab, natalizumab), JAK kinase inhibitors (tofacitinib), cyclosporin or tacrolimus

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Study participants will be randomized to either receive AMT-101 or placebo
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMT-101<br>AMT-101 | Drug: AMT-101<br>* Single or daily dosing at doses A, B, C, D, E, F<br>* Other names: no other name applicable;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebos<br>* Single or daily dosing at doses A, B, C, D, E, F<br>* Other names: no other name applicable;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-emergent adverse events (safety and tolerability) | Single and multiple ascending doses of AMT-101 in healthy adult volunteers and patients with active UC by evaluation of incidence of treatment-related adverse events as assessed by CTCAE v4.03 and Modified Mayo Score criteria. | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (CMax) | To assess the pharmacokinetics of AMT-101 and Total IL-10 in healthy volunteers and subjects with UC. | 14 days | 
| Pharmacodynamics | To assess plasma IL-1Ra concentration in healthy volunteers and subjects with UC. | 14 days |