Phase 1 Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of APVO210 in Healthy Subjects, Patients With Psoriasis, and Patients With Ulcerative Colitis
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 85
- 试验地点
- 1
- 主要终点
- Number of subjects with adverse events
研究概览
简要总结
Phase 1 study in 2 stages with 2 expansion cohorts. The first stage is a single ascending dose (SAD) study of APVO210 in healthy volunteers. The second stage is a multiple ascending dose (MAD) study of APVO210 in healthy volunteers. Two expansion cohorts evaluate multiple doses of APVO210 in psoriasis patients and ulcerative colitis patients.
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)
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
- •Main Inclusion Criteria:
- •Age 18 to 65 years old.
- •Body mass index (BMI) > 18.5 kg/m2 and < 30.0 kg/m2; minimum body weight of 50 kg.
- •Good health and no clinically significant findings on:
- •Physical examination
- •12-lead ECG
- •Clinical laboratory tests (serum chemistry, haematology, coagulation, urine drug screen, and urinalysis (UA))
- •Seated systolic blood pressure (BP) 90 to 140 mm Hg.
- •Seated diastolic BP 60 to 90 mm Hg.
- •Psoriasis Patients (Expansion Cohort):
- •Main Inclusion Criteria:
- •Clinical diagnosis of chronic plaque psoriasis with a disease duration of at least 6 months; patients with concurrent psoriatic arthritis may be enrolled.
- •Psoriasis Area and Severity Index (PASI) score ≥ 12 at baseline.
- •Psoriasis plaque BSA (Body surface area) ≥ 10%
- •PGA (Physician Global Assessment) ≥
- •Age 18 to 65 years old.
- •Body mass index > 18.5 and < 35.0 kg/m2; minimum body weight of 50 kg.
- •Ulcerative Colitis Patients (Expansion Cohort):
- •Main Inclusion Criteria:
- •Moderately to severely active ulcerative colitis as defined by:
- •Baseline Mayo Score of 6 to 12; and
- •Endoscopic sub-score ≥2 as read by central reader
- •Is intolerant, refractory, or only partially responsive to corticosteroids (not including budesonide), immunomodulators (azathioprine [AZA] or 6-mercaptopurine [6-MP], and methotrexate), or biologics.
- •Age 18 to 65 years old.
- •Body mass index > 18.5 and < 35.0 kg/m2; minimum body weight of 50 kg.
排除标准
- •Main Exclusion Criteria
- •Clinically significant manifestation of metabolic; hepatic; renal; haematological; pulmonary; cardiovascular; gastrointestinal; musculoskeletal; dermatological; urogenital; eye, ear, nose, and throat; psychiatric; or neurological disorders.
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.2 times the upper limit of normal (ULN) as defined by the laboratory.
- •Positive hepatitis panel (hepatitis B surface antigen [HBsAg] and anti-hepatitis C virus [HCV]) or positive human immunodeficiency virus (HIV) antibody.
- •Positive Quantiferon tuberculosis (TB) test at Screening Visit.
- •Receipt of live vaccine less than 1 month prior to Check in or plan to receive live vaccine during the study or up to 3 months following End of Treatment visit.
- •Infection in the 4 weeks prior to Check-in that required hospitalization or parenteral antibiotics.
- •Psoriasis Patients (Expansion Cohort):
- •Main Exclusion Criteria:
- •History of malignancy, diagnosed or known to be active or actively treated within the past 5 years, other than resected lesions of low malignant potential, such as basal cell skin cancers or low risk squamous cell carcinomas of the skin.
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times the upper limit of normal (ULN) as defined by the laboratory.
- •Creatinine > 1.5 times ULN as defined by the laboratory.
- •Positive hepatitis panel (hepatitis B surface antigen [HBsAg] and anti-hepatitis C virus [HCV]) or positive human immunodeficiency virus (HIV) antibody.
- •Positive Quantiferon tuberculosis (TB) test at Screening Visit.
- •Receipt of live vaccine less than 1 month prior to Check in or plan to receive live vaccine during the study or up to 3 months following End of Treatment visit.
- •Infection in the 4 weeks prior to Check-in that required hospitalization or parenteral antibiotics.
- •Use of a prescription medication that could have an effect on psoriasis (eg, lithium, systemic steroids, immunosuppressants) during the 14 days before Check-in; use of prescription medications for psoriasis is not permitted until after the Follow-up Visit.
- •Non plaque forms of psoriasis (eg, erythrodermic, guttate, or pustular).
- •Use of biologic agents (eg, adalimumab, etanercept, infliximab, ustekinumab, ixekizumab, secukinumab, guselkumab, tildrakizumab, brodalumab) or psoralen and ultraviolet A (PUVA) within 12 weeks prior to Check-in, ultraviolet B (UVB) phototherapy, use of tanning beds, or use of systemic medications such as methotrexate, cyclosporine A, acitretin, tofacitinib or apremilast within 4 weeks prior to Check-in, or topical anti-psoriasis medications (except emollients) within 2 weeks prior to Check-in.
- •Ulcerative Colitis Patients (Expansion Cohort):
- •Main Exclusion Criteria:
- •Ulcerative colitis requiring immediate surgical, endoscopic, or radiological intervention including massive haemorrhage, perforation and sepsis, suppurative complications, or toxic colon.
- •Stool positive for Clostridium difficile toxin, enteric pathogens, or ova and parasites.
- •Positive hepatitis panel (hepatitis B surface antigen [HBsAg] and anti hepatitis C virus [HCV]) or positive human immunodeficiency virus (HIV) antibody.
- •Positive Quantiferon tuberculosis (TB) test at Screening Visit.
- •Receipt of live vaccine less than 1 month prior to Check in or plan to receive live vaccine during the study or up to 3 months following End of Treatment visit.
- •Infection in the 4 weeks prior to Check-in that required hospitalization or parenteral antibiotics.
- •Use of biologic agents (eg, adalimumab, etanercept, infliximab, ustekinumab, ixekizumab, secukinumab, guselkumab, tildrakizumab, brodalumab) or psoralen and ultraviolet A (PUVA) within 12 weeks prior to Check-in, ultraviolet B (UVB) phototherapy, use of tanning beds, or use of systemic medications such as methotrexate, cyclosporine A, acitretin, tofacitinib or apremilast within 4 weeks prior to Check-in, or topical anti-psoriasis medications (except emollients) within 2 weeks prior to Check-in.
研究组 & 干预措施
Stage 1 (SAD) Cohort 1
6 subjects will receive 2 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: APVO210 (Biological)
Stage 1 (SAD) Cohort 1
6 subjects will receive 2 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: Placebo (Biological)
Stage 1 (SAD) Cohort 2
6 subjects will receive 5 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: Placebo (Biological)
Stage 1 (SAD) Cohort 3
6 subjects will receive 10 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: Placebo (Biological)
Stage 1 (SAD) Cohort 4
6 subjects will receive 20 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: Placebo (Biological)
Stage 1 (SAD) Cohort 8
6 subjects will receive 320 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: Placebo (Biological)
Stage 1 (SAD) Cohort 5
6 subjects will receive 40 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: Placebo (Biological)
Stage 1 (SAD) Cohort 6
6 subjects will receive 80 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: Placebo (Biological)
Stage 1 (SAD) Cohort 7
6 subjects will receive 160 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: Placebo (Biological)
Stage 2 (MAD) Cohort 9
8 subjects will receive 40 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: Placebo (Biological)
Stage 2 (MAD) Cohort 10
8 subjects will receive 80 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: Placebo (Biological)
Stage 2 (MAD) Cohort 11
8 subjects will receive 160 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: Placebo (Biological)
Stage 2 (MAD) Cohort 12
8 subjects will receive 360 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: APVO210 (Biological)
Stage 2 (MAD) Cohort 12
8 subjects will receive 360 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: Placebo (Biological)
Expansion Cohort (Psoriasis)
12 subjects will receive the starting dose for the Psoriasis Patients Expansion Cohort portion of the study will be the recommended dose from Stage 2 of the study of APVO210. It will be a dose that has been demonstrated to be safe and well tolerated by the Safety Monitoring Committee.
8 subjects will receive placebo
干预措施: Placebo (Biological)
Expansion Cohort (Ulcerative Colitis)
12 Subjects will receive the starting dose for the Ulcerative Colitis Patients Expansion Cohort portion of the study will be the recommended dose from Stage 2 of the study of APVO210. It will be a dose that has been demonstrated to be safe and well tolerated by the Safety Monitoring Committee.
8 subjects will receive placebo
干预措施: Placebo (Biological)
Expansion Cohort (Ulcerative Colitis)
12 Subjects will receive the starting dose for the Ulcerative Colitis Patients Expansion Cohort portion of the study will be the recommended dose from Stage 2 of the study of APVO210. It will be a dose that has been demonstrated to be safe and well tolerated by the Safety Monitoring Committee.
8 subjects will receive placebo
干预措施: APVO210 (Biological)
Expansion Cohort (Psoriasis)
12 subjects will receive the starting dose for the Psoriasis Patients Expansion Cohort portion of the study will be the recommended dose from Stage 2 of the study of APVO210. It will be a dose that has been demonstrated to be safe and well tolerated by the Safety Monitoring Committee.
8 subjects will receive placebo
干预措施: APVO210 (Biological)
Stage 2 (MAD) Cohort 11
8 subjects will receive 160 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: APVO210 (Biological)
Stage 2 (MAD) Cohort 10
8 subjects will receive 80 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: APVO210 (Biological)
Stage 2 (MAD) Cohort 9
8 subjects will receive 40 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: APVO210 (Biological)
Stage 1 (SAD) Cohort 8
6 subjects will receive 320 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: APVO210 (Biological)
Stage 1 (SAD) Cohort 7
6 subjects will receive 160 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: APVO210 (Biological)
Stage 1 (SAD) Cohort 6
6 subjects will receive 80 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: APVO210 (Biological)
Stage 1 (SAD) Cohort 5
6 subjects will receive 40 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: APVO210 (Biological)
Stage 1 (SAD) Cohort 4
6 subjects will receive 20 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: APVO210 (Biological)
Stage 1 (SAD) Cohort 3
6 subjects will receive 10 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: APVO210 (Biological)
Stage 1 (SAD) Cohort 2
6 subjects will receive 5 mcg/kg of APVO210 2 subjects will receive placebo
干预措施: APVO210 (Biological)
结局指标
主要结局
Number of subjects with adverse events
时间窗: up to Day 57
Number of subjects with significant changes from baseline laboratory measurements
时间窗: up to Day 57
Number of subjects with clinical significant abnormalities found on physical examination
时间窗: up to Day 57
Number of ulcerative colitis patients with adverse events
时间窗: up to day 141
Number of ulcerative colitis patients with clinically significant abnormalities in electrocardiogram (ECG) results
时间窗: up to day 141
Number of subjects with clinically relevant findings in vital signs
时间窗: up to Day 57
Number of psoriasis patients with adverse events
时间窗: up to day 141
Number of psoriasis patients with clinical significant abnormalities found on physical examination
时间窗: up to day 141
Number of ulcerative colitis patients with clinical significant abnormalities found on physical examination
时间窗: up to day 141
Number of subjects with clinically significant abnormalities in electrocardiogram (ECG) results
时间窗: up to Day 57
Number of psoriasis patients with clinically relevant findings in vital signs
时间窗: up to day 141
Number of psoriasis patients with significant changes from baseline laboratory measurements
时间窗: up to day 141
Number of psoriasis patients with clinically significant abnormalities in electrocardiogram (ECG) results
时间窗: up to day 141
Number of ulcerative colitis patients with clinically relevant findings in vital signs
时间窗: up to day 141
Number of ulcerative colitis patients with significant changes from baseline laboratory measurements
时间窗: up to day 141
Number of subjects with clinically relevant findings in vital signs
时间窗: up to Day 29
Number of subjects with adverse events
时间窗: up to Day 29
Number of subjects with significant changes from baseline laboratory measurements
时间窗: up to Day 29
Number of subjects with clinically significant abnormalities in electrocardiogram (ECG) results
时间窗: up to Day 29
Number of subjects with clinical significant abnormalities found on physical examination
时间窗: up to Day 29
次要结局
- Area under the plasma concentration versus time curve (AUC) for ulcerative colitis patients(Up to day 141)
- Change in number of leukocytes by flow cytometry in psoriasis patients(Up to day 141)
- Change in number of leukocytes by flow cytometry in ulcerative colitis patients(Up to day 141)
- Serum level of Peak Plasma Concentration (Cmax) in ulcerative colitis patients(Up to day 141)
- Area under the plasma concentration versus time curve (AUC)(Up to day 57)
- The number of subjects who develop anti-drug antibodies to APVO210(Up to day 57)
- The number of psoriasis patients who develop anti-drug antibodies to APVO210(Up to day 141)
- The number of ulcerative colitis patients who develop anti-drug antibodies to APVO210(Up to day 141)
- Serum level of Peak Plasma Concentration (Cmax)(Up to day 57)
- Serum level of Peak Plasma Concentration (Cmax) in psoriasis patients(Up to day 141)
- Area under the plasma concentration versus time curve (AUC) for psoriasis patients(Up to day 141)
- Change in cytokine levels by ex-vivo LPS stimulation assay in ulcerative colitis patients.(Up to day 141)
- Change in cytokine levels by ex-vivo LPS stimulation assay in psoriasis patients.(Up to day 141)
- Area under the plasma concentration versus time curve (AUC)(Up to day 29)
- The number of subjects who develop anti-drug antibodies to APVO210(Up to day 29)
- Serum level of Peak Plasma Concentration (Cmax)(Up to day 29)