Ulcerative Colitis (UC)
Conditions
Keywords
ulcertive colitis, IBD, UC
Brief summary
The goal of this clinical trial is to assess the safety, tolerability, and pharmacokinetics (PK) of ATTO-1091 in healthy adults and patients with ulcerative colitis. The main questions it aims to answer are: What medical problems do participants have when taking ATTO-1091? How long does ATTO-1091 stay in the body after dosing? Researchers will compare ATTO-1091 to a placebo (a look-alike substance that contains no drug). Participants will be dosed with ATTO-1091 or a placebo, visit the clinic for checkups and tests, and keep a diary of their symptoms.
Detailed description
This is a 3-part study. Parts 1 and 2 will be a single and multiple ascending dose design, respectively, assessing the safety, tolerability, and PK of ATTO-1091 in healthy adult volunteers. Part 3 will consist of multiple doses in adult participants with ulcerative colitis to assess safety, tolerability, and PK.
Interventions
DRUGATTO-1091
ATTO-1091
DRUGPlacebo
Placebo preparation to match ATTO-1091 dose
Sponsors
Attovia Therapeutics Inc
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Part 1 (SAD) and Part 2 (MAD) in HV will be fully blinded and placebo controlled. Part 3 (MAD) in participants with ulcerative colitis will be open-label active treatment only.
Intervention model description
Single ascending dose, multiple ascending dose, randomized, double-blind, placebo-controlled
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Parts 1\&2 (Healthy Volunteers) Key Inclusion Criteria: * Any sex or gender who is 18 to 60 years old, inclusive, at Screening. * Body weight of 45 to 125 kg, inclusive, and body mass index (BMI) between 18.5 and 35 kg/m2. * Considered in good general health based on medical history, physical exam, 12-lead ECG, screening clinical laboratory findings, and vital signs. * Meets contraception requirements * Negative pregnancy test for participants of childbearing potential. Part 3 (Participants with Ulcerative Colitis) Key Inclusion Criteria: * Any sex or gender who is 18 to 80 years old * Body weight of 45 to 125 kg and BMI between 17.0 and 40.0 kg/m2 * UC diagnosis confirmed by endoscopy and histology ≥3 months prior to Screening * Moderately to severely active UC as defined by Modified Mayo Clinic Score (stool frequency, rectal bleeding, endoscopy) 5 to 9 inclusive, with Mayo endoscopic subscore ≥2 as confirmed by the central reader during Screening * Rectal bleeding subscore ≥1 and stool frequency subscore ≥1 at Screening. * Naïve to treatment with advanced therapies or has had an inadequate response, loss of response, or intolerance to no more than 3 drugs in 2 classes of the following: * Tumor necrosis factor (TNF-α) antagonists * Interleukin IL-12/IL-23 antagonists * Integrin inhibitors * JAK antagonists * S1P receptor agonists * Novel class with biologic-like activity (e.g. TL1A antagonists) * Meets washout criteria for prior UC therapies as specified in the protocol. * Negative pregnancy test for participants of childbearing potential Parts 1\&2 (Healthy Volunteers) Key
Exclusion criteria
* Any clinically significant underlying illness * History of malignancy within 5 years of Screening * History of major surgery within 8 weeks prior to Day 1 or has a major surgery planned during the study * History of uncontrolled asthma requiring systemic corticosteroids or hospitalization for asthma within 6 months prior to Day 1 * History of hypersensitivity (including anaphylaxis) to a biologic medication, vaccine, immunoglobulin product (plasma-derived or recombinant, eg, monoclonal antibody), or to any of the IP excipients * Active hepatitis B virus (HBV) or hepatitis C virus (HCV) or is positive for HIV * Active or latent tuberculosis infection * Smoking more than 20 cigarettes (or cigars, cigarillos, or e-cigarettes equivalent to approximately 40 mg nicotine) per day * History of drug or alcohol abuse * Laboratory values outside of the normal range considered clinically significant by the investigator Part 3 (Participants with Ulcerative Colitis) Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of AEs | 0-169 Days for SAD; 0-204 Days for MAD in HV; 0-141 Days for MAD in UC | The primary analysis will describe the incidence of AEs and laboratory abnormalities. AEs will be coded according to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA, version 28.0 or the current version). Their severity will be graded using the NCI CTCAE v5.0 or the current version. |
| Incidence of laboratory abnormalities | 0-169 Days for SAD; 0-204 Days for MAD in HV; 0-141 Days for MAD in UC | Clinical laboratory parameters (hematologic and blood chemistry) will be summarized by visit |
| Incidence of ECG abnormalities | 0-169 Days for SAD; 0-204 Days for MAD in HV; 0-141 Days for MAD in UC | ECG findings (including QT abnormalities) will be summarized by visit. |
| Incidence of vital sign abnormalities | 0-169 Days for SAD; 0-204 Days for MAD in HV; 0-141 Days for MAD in UC | Vital signs (systolic and diastolic blood pressure, temperature, heart rate) will be summarized by visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Anti-drug Antibodies | 0-169 Days for SAD; 0-204 Days for MAD in HV; 0-141 Days for MAD in UC | Baseline prevelance of ADA, changes in ADA status from prior to the first dose of IP to each applicable post-dose timepoint and ADA titer values for samples confirmed positive for ADA will be evaluated to assess the immunogenicity of single and multiple dose levels of ATT-1091. |
| Peak Plasma Concentration (Cmax) of ATTO-1091 | 0-169 Days for SAD; 0-204 Days for MAD in HV; 0-141 Days for MAD in UC | The pharmacokinetics of single and multiple dose levels of ATTO-1091 in participants will include maximum concentration (Cmax) of ATTO-1091 |
| Circulating Half-life (t1/2) of ATTO-1091 | 0-169 Days for SAD; 0-204 Days for MAD in HV; 0-141 for MAD in UC | The pharmacokinetics of single and multiple dose levels of ATTO-1091 in participants will include half-life (t1/2) of ATTO-1091 |
| Area Under the Plasma Concentration versus Time Curve (AUC) ATTO-1091 | 0-169 Days for SAD; 0-204 Days for MAD in HV; 0-141 for MAD in UC | The pharmacokinetics of single and multiple dose levels of ATTO-1091 in participants will include area under the plasma concentration-time curve (AUC). |
| Clearance Rate (C) for ATTO-1091 | 0-169 Days for SAD; 0-204 Days for MAD in HV; 0-141 for MAD in UC | The pharmacokinetics of single and multiple dose levels of ATTO-1091 in participants will include characterization of the clearance rate (C) of ATTO-1091. |
| Volume of Distribution (V) of ATTO-1091 | 0-169 Days for SAD; 0-204 Days for MAD in HV; 0-141 Days for MAD in UC | The pharmacokinetics of single and multiple dose levels of ATTO-1091 in participants will include characterization of the Volume of distribution (V) of ATTO-1091. |
Contacts
CONTACTMalinda Longphre
STUDY_DIRECTORHubert Chen, MD
Attovia Therapeutics Inc
Outcome results
None listed