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

Ulcerative Colitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03768219
• Other study ID #: 8001
• Status: Terminated
• Phase: Phase 1
• Start date: March 18, 2019
• Est. completion date: June 30, 2020

Study information

• Verified date: May 2021
• Source: Aptevo Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 85
• Est. completion date: June 30, 2020
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Psoriasis
• Ulcer
• Ulcerative Colitis

Intervention

Biological:
• APVO210
APVO210
• Placebo
Placebo is saline based IV infusion, and is identical in appearance to active study drug.

Locations

Country	Name	City	State
Australia	Nucleus Network	Melbourne	Victoria

Sponsors (1)

Lead Sponsor	Collaborator
Aptevo Therapeutics

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with adverse events		up to Day 29
Primary	Number of subjects with clinically relevant findings in vital signs		up to Day 29
Primary	Number of subjects with significant changes from baseline laboratory measurements		up to Day 29
Primary	Number of subjects with clinically significant abnormalities in electrocardiogram (ECG) results		up to Day 29
Primary	Number of subjects with clinical significant abnormalities found on physical examination		up to Day 29
Primary	Number of subjects with adverse events		up to Day 57
Primary	Number of subjects with clinically relevant findings in vital signs		up to Day 57
Primary	Number of subjects with significant changes from baseline laboratory measurements		up to Day 57
Primary	Number of subjects with clinically significant abnormalities in electrocardiogram (ECG) results		up to Day 57
Primary	Number of subjects with clinical significant abnormalities found on physical examination		up to Day 57
Primary	Number of psoriasis patients with adverse events		up to day 141
Primary	Number of psoriasis patients with clinically relevant findings in vital signs		up to day 141
Primary	Number of psoriasis patients with significant changes from baseline laboratory measurements		up to day 141
Primary	Number of psoriasis patients with clinically significant abnormalities in electrocardiogram (ECG) results		up to day 141
Primary	Number of psoriasis patients with clinical significant abnormalities found on physical examination		up to day 141
Primary	Number of ulcerative colitis patients with adverse events		up to day 141
Primary	Number of ulcerative colitis patients with clinically relevant findings in vital signs		up to day 141
Primary	Number of ulcerative colitis patients with significant changes from baseline laboratory measurements		up to day 141
Primary	Number of ulcerative colitis patients with clinically significant abnormalities in electrocardiogram (ECG) results		up to day 141
Primary	Number of ulcerative colitis patients with clinical significant abnormalities found on physical examination		up to day 141
Secondary	The number of subjects who develop anti-drug antibodies to APVO210		Up to day 29
Secondary	The number of subjects who develop anti-drug antibodies to APVO210		Up to day 57
Secondary	The number of psoriasis patients who develop anti-drug antibodies to APVO210		Up to day 141
Secondary	The number of ulcerative colitis patients who develop anti-drug antibodies to APVO210		Up to day 141
Secondary	Serum level of Peak Plasma Concentration (Cmax)		Up to day 29
Secondary	Serum level of Peak Plasma Concentration (Cmax)		Up to day 57
Secondary	Serum level of Peak Plasma Concentration (Cmax) in psoriasis patients		Up to day 141
Secondary	Serum level of Peak Plasma Concentration (Cmax) in ulcerative colitis patients		Up to day 141
Secondary	Area under the plasma concentration versus time curve (AUC)		Up to day 29
Secondary	Area under the plasma concentration versus time curve (AUC)		Up to day 57
Secondary	Area under the plasma concentration versus time curve (AUC) for psoriasis patients		Up to day 141
Secondary	Area under the plasma concentration versus time curve (AUC) for ulcerative colitis patients		Up to day 141
Secondary	Change in number of leukocytes by flow cytometry in psoriasis patients		Up to day 141
Secondary	Change in number of leukocytes by flow cytometry in ulcerative colitis patients		Up to day 141
Secondary	Change in cytokine levels by ex-vivo LPS stimulation assay in psoriasis patients.		Up to day 141
Secondary	Change in cytokine levels by ex-vivo LPS stimulation assay in ulcerative colitis patients.		Up to day 141