A Study to Investigate the Safety, Tolerability and Pharmacokinetics of ABY-035

Sponsor

Affibody (Industry)

Overall Status

Completed

CT.gov ID

NCT02690142

Collaborator

Covance (Industry)

Enrollment

Locations

Arms

23.3

Duration (Months)

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this first-in-human study is to investigate the safety and tolerability of ABY-035 when administered intravenously and subcutaneously, to healthy volunteers and to psoriasis patients.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis Healthy Subjects	Drug: Placebo Drug: ABY-035 i.v. Drug: ABY-035 s.c.	Phase 1

Detailed Description

This first in human study with ABY-035 (a novel IL-17A inhibitor (interleukin 17A)) consists of four Parts. Part A consists of a single ascending intravenous dose study with 40 healthy volunteers divided into five dose cohorts. Each group consists of 8 subjects where 6 subjects will receive ABY-035 and 2 will receive placebo. The subjects will be followed for pharmacokinetic and safety assessments up to Day 95 after dosing.

Part B of the study consists of 6 healthy volunteers who will be given a single subcutaneous dose of ABY-035. The subjects will follow the same study visit schedule as Part A.

Part C of the study will include up to 12 moderate-to-severe psoriasis patients who each patient will be given a single intravenous dose of ABY-035. The patients will follow the same study visit schedule as Part A and B.

Part D of the study will include up to 18 psoriasis patients (mild, moderate or severe). Each patient will participate in 3 or 7 biweekly dosing occasions of subcutaneously administered ABY-035. Patients will be followed regularly for safety, efficacy and pharmacokinetics for 8 weeks post-final dose.

Study Design

Study Type:

Interventional

Actual Enrollment :

72 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase I, Partially-randomised, Partially Double-blinded, Safety, Tolerability and Pharmacokinetic Study of ABY-035 in Healthy Subjects and Psoriasis Patients

Study Start Date :

Feb 1, 2016

Actual Primary Completion Date :

Jan 10, 2018

Actual Study Completion Date :

Jan 10, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ABY-035 i.v. Part A: SAD (single ascending dose) including five different dose cohorts. ABY-035 given as intravenous injections. 6 ABY-035 and 2 placebo in each cohort.	Drug: Placebo Single dose i.v. Drug: ABY-035 i.v. Single dose i.v.
Experimental: ABY-035 s.c. Part B: Bioavailability study where 6 subjects will receive ABY-035 as a single subcutaneous injection.	Drug: ABY-035 s.c. Single dose s.c.
Experimental: ABY-035 i.v. in psoriasis patients Part C: Up to 12 psoriasis patients will receive ABY-035 as a single intravenous injection.	Drug: ABY-035 i.v. Single dose i.v.
Experimental: ABY-035 s.c. in psoriasis patients Part D: Up to 18 patients will receive 3 or 7 biweekly doses of ABY-035 as s.c. injections	Drug: ABY-035 s.c. Single dose s.c.

Outcome Measures

Primary Outcome Measures

Number of Participants With Abnormal Laboratory Values or other Adverse Events [Follow-up visit (Day 141)]
Safety is monitored by Vital signs, 12-lead ECGs, urinalysis, hematology, clinical chemistry, coagulation, proinflammatory cytokines and CRP

Secondary Outcome Measures

AUC (Area Under the Concentration-time curve) of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis through analysis of serum samples [Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 30, Day 31, Day 32, Day 43, Day 57, Day 71, Day 85, Day 95, Day 113, Day 141]
t1/2 (half-life) of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis through analysis of serum samples [Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 30, Day 31, Day 32, Day 43, Day 57, Day 71, Day 85, Day 95, Day 113, Day 141]
Maximum serum concentration (Cmax) of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis through analysis of serum samples [Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 30, Day 31, Day 32, Day 43, Day 57, Day 71, Day 85, Day 95, Day 113, Day 141]
Time of maximum observed plasma concentration of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis through analysis of serum samples [Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 30, Day 31, Day 32, Day 43, Day 57, Day 71, Day 85, Day 95, Day 113, Day 141]
Time of last quantifiable plasma concentration of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis through analysis of serum samples [Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 30, Day 31, Day 32, Day 43, Day 57, Day 71, Day 85, Day 95, Day 113, Day 141]
Mean Residence Time (MRT) of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis through analysis of serum samples [Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 30, Day 31, Day 32, Day 43, Day 57, Day 71, Day 85, Day 95, Day 113, Day 141]
Total plasma clearance of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis through analysis of serum samples [Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 30, Day 31, Day 32, Day 43, Day 57, Day 71, Day 85, Day 95, Day 113, Day 141]
Absolute bioavailability (F) of ABY-035 following a single subcutaneous administration in healthy subjects. [Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 43, Day 71, Day 95]
After single subcutaneous injection
Time immediately prior to first quantifiable concentration of ABY-035 following a single subcutaneous administration in healthy subjects. [Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 43, Day 71, Day 95]
After single subcutaneous injection
Volume of distribution during the terminal elimination phase of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis through analysis of serum samples [Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 30, Day 31, Day 32, Day 43, Day 57, Day 71, Day 85, Day 95, Day 113, Day 141]
Volume of distribution at steady state of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis through analysis of serum samples [Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 30, Day 31, Day 32, Day 43, Day 57, Day 71, Day 85, Day 95, Day 113, Day 141]
Clinical efficacy of ABY-035, using PASI (Psoriasis Area and Disease Index) response, following single dose intravenous administration in patients with moderate-to-severe psoriasis. [Screening, Day -1, Day 2, Day 8, Day 15, Day 17, Day 22, Day 29, Day 31, Day 43, Day 71, Day 57, Day 85, Day 95, Day 113, Day 123, Day 141, Day 151]
Immunogenicity of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis [Day -1, Day 1, Day 15, Day 29, Day 57, Day 85, Day 95, Day 113, Day 141]
Measurement of the occurrence of anti-drug antibodies

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Part A, Part B

Males or females between 18 and 65 years of age
Body mass index (BMI) between 18.0 kg/m2 and 32.0 kg/m2, inclusive. maximum body weight of 120 kg
In good health, as determined by medical history, physical examination, vital signs assessment, 12 lead electrocardiogram (ECG) and clinical laboratory evaluations.
Subjects will have given their written informed consent to participate in the study

In addition for Part C and D

Males or females between 18 and 65 years of age
Body mass index (BMI) between 18.0 kg/m2 and 39.9 kg/m2, inclusive. Minimum body weight of 45 kg
Part C: Patients must have had a diagnosis of moderate to severe plaque type psoriasis at least 6 months prior to administration of the study drug without a documented flare within 30 days prior to Screening. Patients with concurrent psoriatic arthritis may be enrolled.
Part D: Patients must have had a diagnosis of plaque type psoriasis (mild, moderate or severe) at least 6 months prior to administration of the study drug without a documented flare within 30 days prior to Screening. Patients with concurrent psoriatic arthritis may be enrolled.
Part C: Have plaque type psoriasis covering at least 10% of total body surface area (BSA) at Screening and at Baseline (Day 1) and have a PASI score of 12 or greater at Screening and at Baseline (Day 1).
Part D: Have at least one psoriatic lesion

Exclusion criteria:

Part A, Part B, Part C and Part D

Subjects who have any clinically significant medical history, as determined by the investigator
Subjects who smoke more than 15 cigarettes, or equivalent, per day
Alcohol and/or drug abuse
Positive for HIV, Hepatitis B, Hepatitis C, or tuberculosis
Subjects who have received a live vaccination within the 3 months prior to Screening
Subjects who are pregnant or lactating
Subjects who do not agree to use appropriate contraception
Subjects who have a history of anaphylaxis, drug allergy or clinically significant allergic condition (excluding non active hayfever)
Participation in another clinical trial
Subjects who, in the opinion of the investigator, should not participate in this study

In addition for Part C and D

Patients who currently have non plaque forms of psoriasis (eg, erythrodermic, guttate, or pustular)
Patients who have current drug induced psoriasis
Have any history of any use of or have participated in clinical trials for any therapeutic agent directly targeted to any IL 17 cytokine or receptor
Have received phototherapy within 4 weeks prior to Day 1
Patients who have received systemic medications or treatments that could affect psoriasis or PASI evaluation (including, but not limited to, oral or injectable corticosteroids, retinoids, 1,25 dihydroxy vitamin D3 and analogues, fumaric acid esters, psoralens, anti TNF (tumour necrosis factor) biologics, anti IL 12/23 biologics, or herbal treatments), within 5 half lives prior to Day 1 (4 weeks for oral anti psoriatics, 12 weeks for psoralens and PUVA (oral psoralen with ultraviolet A), and 24 weeks for biologics)
Patients who have used topical medications and treatments that could affect psoriasis or PASI evaluation (eg, corticosteroids, coal tar, anthralin, calcipotriene, topical vitamin D derivatives, retinoids, tazarotene, methoxsalen, and trimethyl psoralens) within 2 weeks of administration of IMP (Investigational Medicinal Product)
Patients who have used any systemic immunosuppressants (eg, methotrexate, azathioprine, cyclosporine, 6 thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, or tacrolimus) within 8 weeks of administration of IMP (or 5 half lives, whichever is longer).

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Covance Clinical Research Unit Ltd.	Leeds	United Kingdom	LS2 9LH
2	Covance and Royal Liverpool University Hospital Clinical Research Unit	Liverpool	United Kingdom	L7 8XP
3	Imperial Centre for Translational and Experimental Medicine Imperial College Healthcare NHS Trust Hammersmith Hospital	London	United Kingdom	W12 0HS
4	Medicines Evaluation Unit Ltd	Manchester	United Kingdom	M23 9QZ

Sponsors and Collaborators

Affibody
Covance

Investigators

Principal Investigator: Sunu Valasseri, MBBS, MSc, Covance Ltd

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Affibody

ClinicalTrials.gov Identifier:

NCT02690142

Other Study ID Numbers:

ABY-035-001
2015-004531-13

First Posted:

Feb 24, 2016

Last Update Posted:

Mar 2, 2018

Last Verified:

Mar 1, 2018

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Additional relevant MeSH terms:

Psoriasis

Study Results

No Results Posted as of Mar 2, 2018