Clinical trial NCT04224857: SAD/MAD Study in Healthy Subjects and Adults With UC to Evaluate Safety, Tolerability, PK, PD of AMT-101
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ulcerative Colitis
Lead sponsor: Applied Molecular Transport
Sponsor class: INDUSTRY
First posted: 2020-01-13
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Study participants will be randomized to either receive AMT-101 or placebo
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Treatment-emergent adverse events (safety and tolerability)
timeFrame: 14 days
Secondary outcomes:
measure: Maximum plasma concentration (CMax)
timeFrame: 14 days
measure: Pharmacodynamics
timeFrame: 14 days
Other outcomes:
measure: Incidence of anti-drug antibodies against AMT-101
timeFrame: 14 days
Locations:
city: Tbilisi
country: Georgia
facility: LLC ARENSIA Exploratory Medicine
city: Berlin
country: Germany
facility: Charité Research Organisation GmbH
city: Chisinau
country: Moldova, Republic of
facility: ICS ARENSIA Exploratory Medicine SRL
city: Kyiv
country: Ukraine
facility: Medical Center of Harmoniya krasy, Department of clinical trials
Study officials:
affiliation: Applied Molecular Transport
name: Bittoo Kanwar, MD
role: STUDY_DIRECTOR
References: