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

Aptevo Therapeutics

Status and phase: Terminated; Phase 1

Conditions: Psoriasis; Ulcerative Colitis

Treatments: Biological: Placebo; Biological: APVO210

Study type: Interventional

Funder types: Industry

Identifiers

NCT03768219

8001

Details and patient eligibility

About

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.

Enrollment: 85 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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85 participants in 14 patient groups

Stage 1 (SAD) Cohort 1

Experimental group

Description:

6 subjects will receive 2 mcg/kg of APVO210 2 subjects will receive placebo

Treatment:

Biological: Placebo

Biological: APVO210

Stage 1 (SAD) Cohort 2

Experimental group

Description:

6 subjects will receive 5 mcg/kg of APVO210 2 subjects will receive placebo

Treatment:

Biological: Placebo

Biological: APVO210

Stage 1 (SAD) Cohort 3

Experimental group

Description:

6 subjects will receive 10 mcg/kg of APVO210 2 subjects will receive placebo

Treatment:

Biological: Placebo

Biological: APVO210

Stage 1 (SAD) Cohort 4

Experimental group

Description:

6 subjects will receive 20 mcg/kg of APVO210 2 subjects will receive placebo

Treatment:

Biological: Placebo

Biological: APVO210

Stage 1 (SAD) Cohort 5

Experimental group

Description:

6 subjects will receive 40 mcg/kg of APVO210 2 subjects will receive placebo

Treatment:

Biological: Placebo

Biological: APVO210

Stage 1 (SAD) Cohort 6

Experimental group

Description:

6 subjects will receive 80 mcg/kg of APVO210 2 subjects will receive placebo

Treatment:

Biological: Placebo

Biological: APVO210

Stage 1 (SAD) Cohort 7

Experimental group

Description:

6 subjects will receive 160 mcg/kg of APVO210 2 subjects will receive placebo

Treatment:

Biological: Placebo

Biological: APVO210

Stage 1 (SAD) Cohort 8

Experimental group

Description:

6 subjects will receive 320 mcg/kg of APVO210 2 subjects will receive placebo

Treatment:

Biological: Placebo

Biological: APVO210

Stage 2 (MAD) Cohort 9

Experimental group

Description:

8 subjects will receive 40 mcg/kg of APVO210 2 subjects will receive placebo

Treatment:

Biological: Placebo

Biological: APVO210

Stage 2 (MAD) Cohort 10

Experimental group

Description:

8 subjects will receive 80 mcg/kg of APVO210 2 subjects will receive placebo

Treatment:

Biological: Placebo

Biological: APVO210

Stage 2 (MAD) Cohort 11

Experimental group

Description:

8 subjects will receive 160 mcg/kg of APVO210 2 subjects will receive placebo

Treatment:

Biological: Placebo

Biological: APVO210

Stage 2 (MAD) Cohort 12

Experimental group

Description:

8 subjects will receive 360 mcg/kg of APVO210 2 subjects will receive placebo

Treatment:

Biological: Placebo

Biological: APVO210

Expansion Cohort (Psoriasis)

Experimental group

Description:

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

Treatment:

Biological: Placebo

Biological: APVO210

Expansion Cohort (Ulcerative Colitis)

Experimental group

Description:

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

Treatment:

Biological: Placebo

Biological: APVO210