Clinical trial NCT03768219: Study to Evaluate APVO210 in Healthy Subjects, Patients With Psoriasis, and Patients With Ulcerative Colitis
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Psoriasis
Ulcerative Colitis
Lead sponsor: Aptevo Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-12-07
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of subjects with adverse events
timeFrame: up to Day 29
measure: Number of subjects with clinically relevant findings in vital signs
timeFrame: up to Day 29
measure: Number of subjects with significant changes from baseline laboratory measurements
timeFrame: up to Day 29
measure: Number of subjects with clinically significant abnormalities in electrocardiogram (ECG) results
timeFrame: up to Day 29
measure: Number of subjects with clinical significant abnormalities found on physical examination
timeFrame: up to Day 29
measure: Number of subjects with adverse events
timeFrame: up to Day 57
measure: Number of subjects with clinically relevant findings in vital signs
timeFrame: up to Day 57
measure: Number of subjects with significant changes from baseline laboratory measurements
timeFrame: up to Day 57
measure: Number of subjects with clinically significant abnormalities in electrocardiogram (ECG) results
timeFrame: up to Day 57
measure: Number of subjects with clinical significant abnormalities found on physical examination
timeFrame: up to Day 57
measure: Number of psoriasis patients with adverse events
timeFrame: up to day 141
measure: Number of psoriasis patients with clinically relevant findings in vital signs
timeFrame: up to day 141
measure: Number of psoriasis patients with significant changes from baseline laboratory measurements
timeFrame: up to day 141
measure: Number of psoriasis patients with clinically significant abnormalities in electrocardiogram (ECG) results
timeFrame: up to day 141
measure: Number of psoriasis patients with clinical significant abnormalities found on physical examination
timeFrame: up to day 141
measure: Number of ulcerative colitis patients with adverse events
timeFrame: up to day 141
measure: Number of ulcerative colitis patients with clinically relevant findings in vital signs
timeFrame: up to day 141
measure: Number of ulcerative colitis patients with significant changes from baseline laboratory measurements
timeFrame: up to day 141
measure: Number of ulcerative colitis patients with clinically significant abnormalities in electrocardiogram (ECG) results
timeFrame: up to day 141
measure: Number of ulcerative colitis patients with clinical significant abnormalities found on physical examination
timeFrame: up to day 141
Secondary outcomes:
measure: The number of subjects who develop anti-drug antibodies to APVO210
timeFrame: Up to day 29
measure: The number of subjects who develop anti-drug antibodies to APVO210
timeFrame: Up to day 57
measure: The number of psoriasis patients who develop anti-drug antibodies to APVO210
timeFrame: Up to day 141
measure: The number of ulcerative colitis patients who develop anti-drug antibodies to APVO210
timeFrame: Up to day 141
measure: Serum level of Peak Plasma Concentration (Cmax)
timeFrame: Up to day 29
measure: Serum level of Peak Plasma Concentration (Cmax)
timeFrame: Up to day 57
measure: Serum level of Peak Plasma Concentration (Cmax) in psoriasis patients
timeFrame: Up to day 141
measure: Serum level of Peak Plasma Concentration (Cmax) in ulcerative colitis patients
timeFrame: Up to day 141
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: Up to day 29
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: Up to day 57
measure: Area under the plasma concentration versus time curve (AUC) for psoriasis patients
timeFrame: Up to day 141
measure: Area under the plasma concentration versus time curve (AUC) for ulcerative colitis patients
timeFrame: Up to day 141
measure: Change in number of leukocytes by flow cytometry in psoriasis patients
timeFrame: Up to day 141
measure: Change in number of leukocytes by flow cytometry in ulcerative colitis patients
timeFrame: Up to day 141
measure: Change in cytokine levels by ex-vivo LPS stimulation assay in psoriasis patients.
timeFrame: Up to day 141
measure: Change in cytokine levels by ex-vivo LPS stimulation assay in ulcerative colitis patients.
timeFrame: Up to day 141
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Nucleus Network
state: Victoria
Study officials:
affiliation: Aptevo Therapeutics
name: David Schaaf, MD
role: PRINCIPAL_INVESTIGATOR
References: