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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03768219




Registration number
NCT03768219
Ethics application status
Date submitted
30/11/2018
Date registered
7/12/2018
Date last updated
11/10/2019

Titles & IDs
Public title
Study to Evaluate APVO210 in Healthy Subjects, Patients With Psoriasis, and Patients With Ulcerative Colitis
Scientific 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
Secondary ID [1] 0 0
8001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Psoriasis 0 0
Ulcerative Colitis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Oral and Gastrointestinal 0 0 0 0
Inflammatory bowel disease
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - APVO210
Other interventions - Placebo

Experimental: Stage 1 (SAD) Cohort 1 - 6 subjects will receive 2 mcg/kg of APVO210 2 subjects will receive placebo

Experimental: Stage 1 (SAD) Cohort 2 - 6 subjects will receive 5 mcg/kg of APVO210 2 subjects will receive placebo

Experimental: Stage 1 (SAD) Cohort 3 - 6 subjects will receive 10 mcg/kg of APVO210 2 subjects will receive placebo

Experimental: Stage 1 (SAD) Cohort 4 - 6 subjects will receive 20 mcg/kg of APVO210 2 subjects will receive placebo

Experimental: Stage 1 (SAD) Cohort 5 - 6 subjects will receive 40 mcg/kg of APVO210 2 subjects will receive placebo

Experimental: Stage 1 (SAD) Cohort 6 - 6 subjects will receive 80 mcg/kg of APVO210 2 subjects will receive placebo

Experimental: Stage 1 (SAD) Cohort 7 - 6 subjects will receive 160 mcg/kg of APVO210 2 subjects will receive placebo

Experimental: Stage 1 (SAD) Cohort 8 - 6 subjects will receive 320 mcg/kg of APVO210 2 subjects will receive placebo

Experimental: Stage 2 (MAD) Cohort 9 - 8 subjects will receive 40 mcg/kg of APVO210 2 subjects will receive placebo

Experimental: Stage 2 (MAD) Cohort 10 - 8 subjects will receive 80 mcg/kg of APVO210 2 subjects will receive placebo

Experimental: Stage 2 (MAD) Cohort 11 - 8 subjects will receive 160 mcg/kg of APVO210 2 subjects will receive placebo

Experimental: Stage 2 (MAD) Cohort 12 - 8 subjects will receive 360 mcg/kg of APVO210 2 subjects will receive placebo

Experimental: 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

Experimental: 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


Other interventions: APVO210
APVO210

Other interventions: Placebo
Placebo is saline based IV infusion, and is identical in appearance to active study drug.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of subjects with adverse events
Timepoint [1] 0 0
up to Day 29
Primary outcome [2] 0 0
Number of subjects with clinically relevant findings in vital signs
Timepoint [2] 0 0
up to Day 29
Primary outcome [3] 0 0
Number of subjects with significant changes from baseline laboratory measurements
Timepoint [3] 0 0
up to Day 29
Primary outcome [4] 0 0
Number of subjects with clinically significant abnormalities in electrocardiogram (ECG) results
Timepoint [4] 0 0
up to Day 29
Primary outcome [5] 0 0
Number of subjects with clinical significant abnormalities found on physical examination
Timepoint [5] 0 0
up to Day 29
Primary outcome [6] 0 0
Number of subjects with adverse events
Timepoint [6] 0 0
up to Day 57
Primary outcome [7] 0 0
Number of subjects with clinically relevant findings in vital signs
Timepoint [7] 0 0
up to Day 57
Primary outcome [8] 0 0
Number of subjects with significant changes from baseline laboratory measurements
Timepoint [8] 0 0
up to Day 57
Primary outcome [9] 0 0
Number of subjects with clinically significant abnormalities in electrocardiogram (ECG) results
Timepoint [9] 0 0
up to Day 57
Primary outcome [10] 0 0
Number of subjects with clinical significant abnormalities found on physical examination
Timepoint [10] 0 0
up to Day 57
Primary outcome [11] 0 0
Number of psoriasis patients with adverse events
Timepoint [11] 0 0
up to day 141
Primary outcome [12] 0 0
Number of psoriasis patients with clinically relevant findings in vital signs
Timepoint [12] 0 0
up to day 141
Primary outcome [13] 0 0
Number of psoriasis patients with significant changes from baseline laboratory measurements
Timepoint [13] 0 0
up to day 141
Primary outcome [14] 0 0
Number of psoriasis patients with clinically significant abnormalities in electrocardiogram (ECG) results
Timepoint [14] 0 0
up to day 141
Primary outcome [15] 0 0
Number of psoriasis patients with clinical significant abnormalities found on physical examination
Timepoint [15] 0 0
up to day 141
Primary outcome [16] 0 0
Number of ulcerative colitis patients with adverse events
Timepoint [16] 0 0
up to day 141
Primary outcome [17] 0 0
Number of ulcerative colitis patients with clinically relevant findings in vital signs
Timepoint [17] 0 0
up to day 141
Primary outcome [18] 0 0
Number of ulcerative colitis patients with significant changes from baseline laboratory measurements
Timepoint [18] 0 0
up to day 141
Primary outcome [19] 0 0
Number of ulcerative colitis patients with clinically significant abnormalities in electrocardiogram (ECG) results
Timepoint [19] 0 0
up to day 141
Primary outcome [20] 0 0
Number of ulcerative colitis patients with clinical significant abnormalities found on physical examination
Timepoint [20] 0 0
up to day 141
Secondary outcome [1] 0 0
The number of subjects who develop anti-drug antibodies to APVO210
Timepoint [1] 0 0
Up to day 29
Secondary outcome [2] 0 0
The number of subjects who develop anti-drug antibodies to APVO210
Timepoint [2] 0 0
Up to day 57
Secondary outcome [3] 0 0
The number of psoriasis patients who develop anti-drug antibodies to APVO210
Timepoint [3] 0 0
Up to day 141
Secondary outcome [4] 0 0
The number of ulcerative colitis patients who develop anti-drug antibodies to APVO210
Timepoint [4] 0 0
Up to day 141
Secondary outcome [5] 0 0
Serum level of Peak Plasma Concentration (Cmax)
Timepoint [5] 0 0
Up to day 29
Secondary outcome [6] 0 0
Serum level of Peak Plasma Concentration (Cmax)
Timepoint [6] 0 0
Up to day 57
Secondary outcome [7] 0 0
Serum level of Peak Plasma Concentration (Cmax) in psoriasis patients
Timepoint [7] 0 0
Up to day 141
Secondary outcome [8] 0 0
Serum level of Peak Plasma Concentration (Cmax) in ulcerative colitis patients
Timepoint [8] 0 0
Up to day 141
Secondary outcome [9] 0 0
Area under the plasma concentration versus time curve (AUC)
Timepoint [9] 0 0
Up to day 29
Secondary outcome [10] 0 0
Area under the plasma concentration versus time curve (AUC)
Timepoint [10] 0 0
Up to day 57
Secondary outcome [11] 0 0
Area under the plasma concentration versus time curve (AUC) for psoriasis patients
Timepoint [11] 0 0
Up to day 141
Secondary outcome [12] 0 0
Area under the plasma concentration versus time curve (AUC) for ulcerative colitis patients
Timepoint [12] 0 0
Up to day 141
Secondary outcome [13] 0 0
Change in number of leukocytes by flow cytometry in psoriasis patients
Timepoint [13] 0 0
Up to day 141
Secondary outcome [14] 0 0
Change in number of leukocytes by flow cytometry in ulcerative colitis patients
Timepoint [14] 0 0
Up to day 141
Secondary outcome [15] 0 0
Change in cytokine levels by ex-vivo LPS stimulation assay in psoriasis patients.
Timepoint [15] 0 0
Up to day 141
Secondary outcome [16] 0 0
Change in cytokine levels by ex-vivo LPS stimulation assay in ulcerative colitis patients.
Timepoint [16] 0 0
Up to day 141

Eligibility
Key inclusion criteria
Main

- 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

- 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

- 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.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key 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

- 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

- 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Aptevo Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03768219
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David Schaaf, MD
Address 0 0
Aptevo Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications