Study to Evaluate APVO210 in Healthy Subjects, Patients With Psoriasis, and Patients With Ulcerative Colitis

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Psoriasis, Ulcerative Colitis

Intervention / Treatment
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* Biological: APVO210
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) ≥ 3. 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: SAD: Randomized, double-blind, placebo-controlled, sequential cohort-group study with a sentinel subject design MAD: Randomized, double-blind, placebo-controlled, sequential cohort-group study Psoriasis Expansion Cohort: Randomized, double-blind, placebo-controlled study Ulcerative Colitis Expansion Cohort: Randomized, double-blind, placebo-controlled study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stage 1 (SAD) Cohort 1<br>6 subjects will receive 2 mcg/kg of APVO210 2 subjects will receive placebo | Biological: APVO210<br>* APVO210<br>Biological: Placebo<br>* Placebo is saline based IV infusion, and is identical in appearance to active study drug.<br>|
| Experimental: Stage 1 (SAD) Cohort 2<br>6 subjects will receive 5 mcg/kg of APVO210 2 subjects will receive placebo | Biological: APVO210<br>* APVO210<br>Biological: Placebo<br>* Placebo is saline based IV infusion, and is identical in appearance to active study drug.<br>|
| Experimental: Stage 1 (SAD) Cohort 3<br>6 subjects will receive 10 mcg/kg of APVO210 2 subjects will receive placebo | Biological: APVO210<br>* APVO210<br>Biological: Placebo<br>* Placebo is saline based IV infusion, and is identical in appearance to active study drug.<br>|
| Experimental: Stage 1 (SAD) Cohort 4<br>6 subjects will receive 20 mcg/kg of APVO210 2 subjects will receive placebo | Biological: APVO210<br>* APVO210<br>Biological: Placebo<br>* Placebo is saline based IV infusion, and is identical in appearance to active study drug.<br>|
| Experimental: Stage 1 (SAD) Cohort 5<br>6 subjects will receive 40 mcg/kg of APVO210 2 subjects will receive placebo | Biological: APVO210<br>* APVO210<br>Biological: Placebo<br>* Placebo is saline based IV infusion, and is identical in appearance to active study drug.<br>|
| Experimental: Stage 1 (SAD) Cohort 6<br>6 subjects will receive 80 mcg/kg of APVO210 2 subjects will receive placebo | Biological: APVO210<br>* APVO210<br>Biological: Placebo<br>* Placebo is saline based IV infusion, and is identical in appearance to active study drug.<br>|
| Experimental: Stage 1 (SAD) Cohort 7<br>6 subjects will receive 160 mcg/kg of APVO210 2 subjects will receive placebo | Biological: APVO210<br>* APVO210<br>Biological: Placebo<br>* Placebo is saline based IV infusion, and is identical in appearance to active study drug.<br>|
| Experimental: Stage 1 (SAD) Cohort 8<br>6 subjects will receive 320 mcg/kg of APVO210 2 subjects will receive placebo | Biological: APVO210<br>* APVO210<br>Biological: Placebo<br>* Placebo is saline based IV infusion, and is identical in appearance to active study drug.<br>|
| Experimental: Stage 2 (MAD) Cohort 9<br>8 subjects will receive 40 mcg/kg of APVO210 2 subjects will receive placebo | Biological: APVO210<br>* APVO210<br>Biological: Placebo<br>* Placebo is saline based IV infusion, and is identical in appearance to active study drug.<br>|
| Experimental: Stage 2 (MAD) Cohort 10<br>8 subjects will receive 80 mcg/kg of APVO210 2 subjects will receive placebo | Biological: APVO210<br>* APVO210<br>Biological: Placebo<br>* Placebo is saline based IV infusion, and is identical in appearance to active study drug.<br>|
| Experimental: Stage 2 (MAD) Cohort 11<br>8 subjects will receive 160 mcg/kg of APVO210 2 subjects will receive placebo | Biological: APVO210<br>* APVO210<br>Biological: Placebo<br>* Placebo is saline based IV infusion, and is identical in appearance to active study drug.<br>|
| Experimental: Stage 2 (MAD) Cohort 12<br>8 subjects will receive 360 mcg/kg of APVO210 2 subjects will receive placebo | Biological: APVO210<br>* APVO210<br>Biological: Placebo<br>* Placebo is saline based IV infusion, and is identical in appearance to active study drug.<br>|
| Experimental: Expansion Cohort (Psoriasis)<br>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 | Biological: APVO210<br>* APVO210<br>Biological: Placebo<br>* Placebo is saline based IV infusion, and is identical in appearance to active study drug.<br>|
| Experimental: Expansion Cohort (Ulcerative Colitis)<br>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 | Biological: APVO210<br>* APVO210<br>Biological: Placebo<br>* Placebo is saline based IV infusion, and is identical in appearance to active study drug.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events |  | up to Day 29 | 
| Number of subjects with clinically relevant findings in vital signs |  | up to Day 29 | 
| Number of subjects with significant changes from baseline laboratory measurements |  | up to Day 29 | 
| Number of subjects with clinically significant abnormalities in electrocardiogram (ECG) results |  | up to Day 29 | 
| Number of subjects with clinical significant abnormalities found on physical examination |  | up to Day 29 | 
| Number of subjects with adverse events |  | up to Day 57 | 
| Number of subjects with clinically relevant findings in vital signs |  | up to Day 57 | 
| Number of subjects with significant changes from baseline laboratory measurements |  | up to Day 57 | 
| Number of subjects with clinically significant abnormalities in electrocardiogram (ECG) results |  | up to Day 57 | 
| Number of subjects with clinical significant abnormalities found on physical examination |  | up to Day 57 | 
| Number of psoriasis patients with adverse events |  | up to day 141 | 
| Number of psoriasis patients with clinically relevant findings in vital signs |  | up to day 141 | 
| Number of psoriasis patients with significant changes from baseline laboratory measurements |  | up to day 141 | 
| Number of psoriasis patients with clinically significant abnormalities in electrocardiogram (ECG) results |  | up to day 141 | 
| Number of psoriasis patients with clinical significant abnormalities found on physical examination |  | up to day 141 | 
| Number of ulcerative colitis patients with adverse events |  | up to day 141 | 
| Number of ulcerative colitis patients with clinically relevant findings in vital signs |  | up to day 141 | 
| Number of ulcerative colitis patients with significant changes from baseline laboratory measurements |  | up to day 141 | 
| Number of ulcerative colitis patients with clinically significant abnormalities in electrocardiogram (ECG) results |  | up to day 141 | 
| Number of ulcerative colitis patients with clinical significant abnormalities found on physical examination |  | up to day 141 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of subjects who develop anti-drug antibodies to APVO210 |  | Up to day 29 | 
| 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 29 | 
| 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 | 
| 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 29 | 
| Area under the plasma concentration versus time curve (AUC) |  | Up to day 57 | 
| Area under the plasma concentration versus time curve (AUC) for psoriasis patients |  | Up to day 141 | 
| 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 | 
| Change in cytokine levels by ex-vivo LPS stimulation assay in psoriasis patients. |  | Up to day 141 | 
| Change in cytokine levels by ex-vivo LPS stimulation assay in ulcerative colitis patients. |  | Up to day 141 |