SAD/MAD Study in Healthy Subjects and Adults With UC to Evaluate Safety, Tolerability, PK, PD of AMT-101 (AURIGA1)

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

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.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: AMT-101; Drug: Placebos

Detailed Description

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

1. naïve to anti-TNFα therapy or
2. have failed or demonstrated intolerance to anti-TNF-α therapy.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• Georgia
  • Tbilisi, Georgia
    • LLC Arensia Exploratory Medicine
• Germany
  • Berlin, Germany
    • Charité Research Organisation GmbH
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
    • ICS ARENSIA Exploratory Medicine SRL
• Ukraine
  • Kyiv, Ukraine
    • Medical Center of Harmoniya krasy, Department of clinical trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of anti-drug antibodies against AMT-101	Incidence of anti-drug antibodies against AMT-101 in healthy adult volunteers and subjects with UC.	14 days

Collaborators and Investigators

• Sponsor: Applied Molecular Transport
• Investigators: Study Director: Bittoo Kanwar, MD, Applied Molecular Transport

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): April 30, 2020
• Study Completion (Actual): April 30, 2020

Study Registration Dates

• First Submitted: May 23, 2019
• First Submitted That Met QC Criteria: January 8, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): October 28, 2020
• Last Update Submitted That Met QC Criteria: October 26, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: AMT-101-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No