A Phase 1B Open-label/Phase 2 Double-blind Placebo- Controlled Study for Pharmacodynamic (PD) Activity, Pharmacokinetics (PK), Safety, and Tolerability of KAN-101 In Patients With Celiac Disease (CeD)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 128
- 试验地点
- 36
- 主要终点
- Incidence and Severity of TEAEs as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) in Part A
研究概览
简要总结
This study is to evaluate the Pharmacodynamic (PD), safety, tolerability, Pharmacokinetic (PK), and plasma biomarker response of KAN-101 in participants with Celiac Disease (CeD).
详细描述
The study is a 3-part, multicenter Phase 1b/2 study of KAN-101 in participants with Celiac Disease (CeD) on a gluten free diet (GFD). The 3 parts include:
- Part A - Open-label, multiple ascending dose
- Part B - Double-blind, placebo-controlled, parallel design
- Part C - Double-blind, placebo-controlled, parallel design
Part A is a Phase 1b, open-label, multiple ascending dose (MAD) study design to assess the safety, tolerability, and pharmacokinetics (PK) of KAN-101 in adult participants (18 to 70 years inclusive) with histology-confirmed CeD. Up to 12 participants who meet study inclusion/exclusion criteria will receive 1 of 2 dose levels of KAN-101. The overall study duration will be about 56 days, including up to 28 days of screening, 7 days of treatment and 21 days of follow up. There will be a gluten challenge test (GC) on Day 15.
Parts B and C are Phase 2, double-blind, placebo-controlled, parallel design study to characterize the biomarker response following GC, safety, tolerability, and PK of KAN-101 in adult participants with histology-confirmed CeD. Approximately 16 participants (4 participants per dose group) will be enrolled in Part B and 104 participants (26 participants per dose group) enrolled into Part C. Participants will be randomized 1:1:1:1 and stratified by participation in a biopsy substudy to 4 treatment groups: placebo and 3 treatment groups with KAN-101 doses based on information obtained from Part A.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Part A is open label Part B and Part C are a double-blinded study. Study participants and their caregivers, investigators and other site staff, and sponsor staff involved in the study team will be blinded.
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Previous diagnosis of celiac disease based on histology and positive celiac serology
- •HLA-DQ2.5 genotype
- •Gluten-free diet for at least 12 months
- •Negative or weak positive for transglutaminase IgA and negative or weak positive for DGP-IgA/IgG during screening
排除标准
- •Refractory celiac disease
- •HLA-DQ8 genotype
- •Previous oral gluten challenge within 12 months
- •Selective IgA deficiency
- •Diagnosis of Type-1 diabetes
- •Active gastrointestinal diseases
- •History of dermatitis herpetiformis
研究组 & 干预措施
Cohort 1 in Part A
All eligible Part A participants will receive 3 intravenous (IV) infusions of KAN-101 Dose 1
干预措施: Cohort 1 in Part A (Drug)
Cohort 2 in Part A
All eligible Part A participants will receive 3 intravenous (IV) infusions of KAN-101 Dose 2
干预措施: Cohort 2 in Part A (Drug)
Group 2 in Part B and Part C
All eligible Part B and Part C participants will receive 3 intravenous (IV) infusions of KAN-101 Dose 3
干预措施: Group 2 in Part B and Part C (Drug)
Group 3 in Part B and Part C
All eligible Part B and Part C participants will receive 3 intravenous (IV) infusions of KAN-101 Dose 4
干预措施: Group 3 in Part B and Part C (Drug)
Group 4 in Part B and Part C
All eligible Part B and Part C participants will receive 3 intravenous (IV) infusions of KAN-101 Dose 5
干预措施: Group 4 in Part B and Part C (Drug)
Group 1 in Part B and Part C
All eligible Part B and Part C participants will receive 3 intravenous (IV) infusions of placebo
干预措施: Placebo: Group 1 in Part B and Part C (Other)
结局指标
主要结局
Incidence and Severity of TEAEs as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) in Part A
时间窗: From screening until the safety follow-up visit on Day 28
An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious adverse events. SAE was defined as any untoward medical occurrence that, at any dose resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. According to NCI CTCAE version 5: Grade 1= mild AE; Grade 2= moderate AE; Grade 3=severe AE; Grade 4= life-threatening consequences and urgent intervention indicated; Grade 5= death related to AE.
Change in Pre- and Post-Gluten Challenge (GC) IL-2 Response From Baseline to Day 15
时间窗: From Baseline screening to Day 15
CeD increases the circulating level of IL-2. Plasma samples were collected to assess the magnitude of biomarker response of IL-2 at the baseline screening visit pre-GC and again post-GC on Day 15 after 3 doses of KAN-101, the IL-2 response to GC is the difference of IL-2 between pre-GC and post-GC.
Change in IL-2 Response From Day 15 Pre-GC to Day 15 Post GC
时间窗: 0 (pre-GC) and 4 hours post-GC on Day 15
CeD increases the circulating level of IL-2. Plasma samples were collected to assess the magnitude of biomarker response of IL-2 at the baseline screening visit pre-GC and again post-GC on Day 15 after 3 doses of KAN-101, the IL-2 response to GC is the difference of IL-2 between pre-GC and post-GC.
次要结局
- KAN-101 Plasma Exposure in Part B and Part C: t½(Pre-dose, end of infusion, 2.5 hours, and 4 hours after infusion start on Day 1 and Day 7)
- KAN-101 Plasma Exposure in Part A: AUCinf(Pre-dose, end of infusion, 45 minutes, 1 hour, 1.5 hour, 2.5 hours, 4.5 hours and 7 hours after infusion start on Day 1 and Day 7)
- KAN-101 Plasma Exposure in Part A: AUClast(Pre-dose, end of infusion, 45 minutes, 1 hour, 1.5 hour, 2.5 hours, 4.5 hours and 7 hours after infusion start on Day 1 and Day 7)
- KAN-101 Plasma Exposure in Part A: Cmax(Pre-dose, end of infusion, 45 minutes, 1 hour, 1.5 hour, 2.5 hours, 4.5 hours and 7 hours after infusion start on Day 1 and Day 7)
- KAN-101 Plasma Exposure in Part A: Tmax(Pre-dose, end of infusion, 45 minutes, 1 hour, 1.5 hour, 2.5 hours, 4.5 hours and 7 hours after infusion start on Day 1 and Day 7)
- KAN-101 Plasma Exposure in Part A: t½(Pre-dose, end of infusion, 45 minutes, 1 hour, 1.5 hour, 2.5 hours, 4.5 hours and 7 hours after infusion start on Day 1 and Day 7)
- KAN-101 Plasma Exposure in Part B and Part C: AUCinf(Pre-dose, end of infusion, 2.5 hours, and 4 hours after infusion start on Day 1 and Day 7)
- KAN-101 Plasma Exposure in Part B and Part C: AUClast(Pre-dose, end of infusion, 2.5 hours, and 4 hours after infusion start on Day 1 and Day 7)
- KAN-101 Plasma Exposure in Part B and Part C: Cmax(Pre-dose, end of infusion, 2.5 hours, and 4 hours after infusion start on Day 1 and Day 7)
- KAN-101 Plasma Exposure in Part B and Part C: Tmax(Pre-dose, end of infusion, 2.5 hours, and 4 hours after infusion start on Day 1 and Day 7)
- Incidence and Severity of TEAE as Assessed by the CTCAE in Part B(From the time the participant provided informed consent through Week 52)
- Incidence and Severity of TEAE as Assessed by the CTCAE in Part C(From the time the participant provided informed consent through Week 52)