A Phase 1, Multi-Part, Single Ascending Dose and Multiple Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of ATTO 1091 in Healthy Adult Volunteers and Patients With Ulcerative Colitis
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 96
- 主要终点
- Incidence of AEs
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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/m
- •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
排除标准
- •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 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 known primary immunodeficiency or is considered immunocompromised
- •Has been treated for a parasitic infection in the past 6 months
- •Participant has active HBV or HCV or is positive for HIV
- •Participant has active or latent TB
- •Stool positive for Clostridioides difficile toxin at Screening
- •Concomitant primary sclerosing cholangitis.
- •History of active major depressive episode or suicidal ideation
- •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
- •Diagnosis of non-UC or confounding GI conditions including Crohn's disease, indeterminate colitis, microscopic colitis, ischemic or radiation colitis.
- •Disease limited to isolated ulcerative proctitis (<15 cm).
- •Unresected colonic dysplasia or unresected adenomatous colonic polyps, fulminant colitis, toxic megacolon, bowel perforation, current colonic strictures, fistulae, stoma, ileostomy, colostomy, abdominal abscess, or anticipated need for colectomy during the study.
- •History of extensive colonic resection
- •History of drug or alcohol abuse
- •Laboratory values outside of the normal range considered clinically significant by the investigator
研究组 & 干预措施
ATTO-1091 Single dose SC
ATTO-1091 Dose level cohorts receiving a single dose SC
干预措施: ATTO-1091 (Drug)
ATTO-1091 Multiple dose SC
ATTO-1091 Dose level cohorts receiving multiple SC doses
干预措施: ATTO-1091 (Drug)
Placebo single dose SC
Placebo preparation to match Experimental Arm with single dose SC
干预措施: Placebo (Drug)
Placebo multiple dose SC
Placebo preparation to match Experimental Arm administered in multiple SC doses
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of AEs
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Incidence of Anti-drug Antibodies(0-169 Days for SAD; 0-204 Days for MAD in HV; 0-141 Days for MAD in UC)
- 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)
- 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)
- 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)
- Clearance Rate (C) for ATTO-1091(0-169 Days for SAD; 0-204 Days for MAD in HV; 0-141 for MAD in UC)
- 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)