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

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ClinicalTrials.gov Identifier: NCT03768219
Recruitment Status : Recruiting
First Posted : December 7, 2018
Last Update Posted : March 28, 2019
Sponsor:
Information provided by (Responsible Party):
Aptevo Therapeutics

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.

Condition or disease Intervention/treatment Phase
Psoriasis Ulcerative Colitis Biological: APVO210 Biological: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 144 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
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

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : March 18, 2019
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : September 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Stage 1 (SAD) Cohort 1
6 subjects will receive 2 mcg/kg of APVO210 2 subjects will receive placebo
Biological: APVO210
APVO210

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Biological: APVO210
APVO210

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

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

Biological: APVO210
APVO210

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




Primary Outcome Measures :
  1. Number of subjects with adverse events [ Time Frame: up to Day 29 ]
  2. Number of subjects with clinically relevant findings in vital signs [ Time Frame: up to Day 29 ]
  3. Number of subjects with significant changes from baseline laboratory measurements [ Time Frame: up to Day 29 ]
  4. Number of subjects with clinically significant abnormalities in electrocardiogram (ECG) results [ Time Frame: up to Day 29 ]
  5. Number of subjects with clinical significant abnormalities found on physical examination [ Time Frame: up to Day 29 ]
  6. Number of subjects with adverse events [ Time Frame: up to Day 57 ]
  7. Number of subjects with clinically relevant findings in vital signs [ Time Frame: up to Day 57 ]
  8. Number of subjects with significant changes from baseline laboratory measurements [ Time Frame: up to Day 57 ]
  9. Number of subjects with clinically significant abnormalities in electrocardiogram (ECG) results [ Time Frame: up to Day 57 ]
  10. Number of subjects with clinical significant abnormalities found on physical examination [ Time Frame: up to Day 57 ]
  11. Number of psoriasis patients with adverse events [ Time Frame: up to day 141 ]
  12. Number of psoriasis patients with clinically relevant findings in vital signs [ Time Frame: up to day 141 ]
  13. Number of psoriasis patients with significant changes from baseline laboratory measurements [ Time Frame: up to day 141 ]
  14. Number of psoriasis patients with clinically significant abnormalities in electrocardiogram (ECG) results [ Time Frame: up to day 141 ]
  15. Number of psoriasis patients with clinical significant abnormalities found on physical examination [ Time Frame: up to day 141 ]
  16. Number of ulcerative colitis patients with adverse events [ Time Frame: up to day 141 ]
  17. Number of ulcerative colitis patients with clinically relevant findings in vital signs [ Time Frame: up to day 141 ]
  18. Number of ulcerative colitis patients with significant changes from baseline laboratory measurements [ Time Frame: up to day 141 ]
  19. Number of ulcerative colitis patients with clinically significant abnormalities in electrocardiogram (ECG) results [ Time Frame: up to day 141 ]
  20. Number of ulcerative colitis patients with clinical significant abnormalities found on physical examination [ Time Frame: up to day 141 ]

Secondary Outcome Measures :
  1. The number of subjects who develop anti-drug antibodies to APVO210 [ Time Frame: Up to day 29 ]
  2. The number of subjects who develop anti-drug antibodies to APVO210 [ Time Frame: Up to day 57 ]
  3. The number of psoriasis patients who develop anti-drug antibodies to APVO210 [ Time Frame: Up to day 141 ]
  4. The number of ulcerative colitis patients who develop anti-drug antibodies to APVO210 [ Time Frame: Up to day 141 ]
  5. Serum level of Peak Plasma Concentration (Cmax) [ Time Frame: Up to day 29 ]
  6. Serum level of Peak Plasma Concentration (Cmax) [ Time Frame: Up to day 57 ]
  7. Serum level of Peak Plasma Concentration (Cmax) in psoriasis patients [ Time Frame: Up to day 141 ]
  8. Serum level of Peak Plasma Concentration (Cmax) in ulcerative colitis patients [ Time Frame: Up to day 141 ]
  9. Area under the plasma concentration versus time curve (AUC) [ Time Frame: Up to day 29 ]
  10. Area under the plasma concentration versus time curve (AUC) [ Time Frame: Up to day 57 ]
  11. Area under the plasma concentration versus time curve (AUC) for psoriasis patients [ Time Frame: Up to day 141 ]
  12. Area under the plasma concentration versus time curve (AUC) for ulcerative colitis patients [ Time Frame: Up to day 141 ]
  13. Change in number of leukocytes by flow cytometry in psoriasis patients [ Time Frame: Up to day 141 ]
  14. Change in number of leukocytes by flow cytometry in ulcerative colitis patients [ Time Frame: Up to day 141 ]
  15. Change in cytokine levels by ex-vivo LPS stimulation assay in psoriasis patients. [ Time Frame: Up to day 141 ]
  16. Change in cytokine levels by ex-vivo LPS stimulation assay in ulcerative colitis patients. [ Time Frame: Up to day 141 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03768219


Contacts
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Contact: David Schaaf, MD 206-859-6655 schaafd@apvo.com
Contact: Katy Swanson 206-838-0571 swansonk@apvo.com

Locations
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Australia, Victoria
Nucleus Network Recruiting
Melbourne, Victoria, Australia, 3004
Contact: Jason Lickliter, MD    03-8593-9800    j.lickliter@nucleusnetwork.com.au   
Contact: Cameron Johnson       c.johnson@nucleusnetwork.com.au   
Sponsors and Collaborators
Aptevo Therapeutics
Investigators
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Principal Investigator: David Schaaf, MD Aptevo Therapeutics

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Responsible Party: Aptevo Therapeutics
ClinicalTrials.gov Identifier: NCT03768219     History of Changes
Other Study ID Numbers: 8001
First Posted: December 7, 2018    Key Record Dates
Last Update Posted: March 28, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Psoriasis
Colitis
Ulcer
Colitis, Ulcerative
Skin Diseases, Papulosquamous
Skin Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases