A Study to Evaluate the Effects of Single and Multiple Oral Doses of GLPG3970

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety and tolerability of GLPG3970 in healthy volunteers after single oral administrations of GLPG3970 (SAD), compared to placebo (part 1 and 1bis) and after multiple (for 14 days) oral administrations of GLPG3970 (MAD), compared to placebo (part 2). The effect of food (FE) (high-fat, high calorie) on the pharmacokinetics of GLPG3970 and the relative bioavailability (rBA) of an oral solution versus a solid formulation will be assessed (part 3 and 3bis). Part 4 of the study is to evaluate the safety and tolerability of GLPG3970 in subjects with moderate to severe psoriasis when administered daily for 6 weeks.

Official Title
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A First-in-human, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GLPG3970 Single and Multiple Ascending Doses in Adult Healthy Male Subjects, and in Psoriasis Subjects When Administered Daily for 6 Weeks

Conditions
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Healthy, Psoriasis

Intervention / Treatment
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* Drug: GLPG3970 oral solution
* Drug: Placebo oral solution
* Drug: GLPG3970 capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Part 1, 1bis, 2, 3 and 3bis: Male between 18-55 years of age (extremes included), on the date of signing the informed consent form (ICF). A body mass index (BMI) between 18-30 kg/m2, inclusive. Judged to be in good health by the investigator based upon the results of a medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and fasting clinical laboratory safety tests available at screening and prior to randomization. Hemoglobin must not be below the lower limit of normal range. Bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) must be no greater than 1.5x upper limit of normal range (ULN). Other clinical laboratory safety test results must be within the reference ranges, or test results that are outside the reference ranges need to be considered not clinically significant in the opinion of the investigator. This list only contains the key inclusion criteria for the healthy volunteers part of the study. Inclusion criteria for Part 4: Male or female between 18-65 years of age (extremes included), on the date of signing the ICF. Diagnosed with plaque psoriasis ≥6 months. Screening Psoriasis Area and Severity Index (PASI) ≥12 (moderate to severe) and affected body surface area (BSA) ≥10%. A body mass index (BMI) between 18-35 kg/m2, inclusive. This list only contains the key inclusion criteria for Part 4 of the study. Exclusion Criteria for Part 1, 1bis, 2, 3 and 3bis: Known hypersensitivity to the Investigational Medicinal Product (IMP) ingredients or history of a significant allergic reaction to IMP ingredients as determined by the investigator. Positive serology for hepatitis B virus surface antigen (HBsAg) or hepatitis C virus or history of hepatitis from any cause with the exception of hepatitis A that was resolved at least 3 months prior to first dosing of the IMP. History of or a current immunosuppressive condition (e.g. human immunodeficiency virus [HIV] infection). This list only contains the key exclusion criteria for the healthy volunteers part of the study. Exclusion criteria for Part 4: Subject has evidence of skin conditions other than psoriasis (e.g., eczema) at the time of screening or baseline visit that would interfere with the evaluation of psoriasis. Subject is unable to discontinue systemic therapies and/or topical therapies for the treatment of psoriasis and cannot discontinue phototherapy (UVB or PUVA) from signing of the ICF up to the end of the study. This list only contains the key inclusion criteria for Part 4 of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Part 1 and 1bis (SAD), Part 2 (MAD) and Part 4 (psoriasis subjects) are randomized, double-blind, placebo-controlled; Part 3 (FE-rBA) and Part 3bis (FE) are randomized, open-label.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GLPG3970 SAD<br>Single doses of GLPG3970 at up to 6 dose levels in ascending order | Drug: GLPG3970 oral solution<br>* GLPG3970 for oral administration<br>|
| Placebo Comparator: Placebo SAD<br>Single doses of placebo | Drug: Placebo oral solution<br>* Placebo for oral administration<br>|
| Experimental: GLPG3970 MAD<br>Multiple doses of GLPG3970 at up to 4 dose levels in ascending order, daily for 14 days | Drug: GLPG3970 oral solution<br>* GLPG3970 for oral administration<br>|
| Placebo Comparator: Placebo MAD<br>Multiple doses of placebo | Drug: Placebo oral solution<br>* Placebo for oral administration<br>|
| Experimental: GLPG3970 FE-rBA<br>Single dose of GLPG3970 in fed and fasted state | Drug: GLPG3970 oral solution<br>* GLPG3970 for oral administration<br>Drug: GLPG3970 capsule<br>* GLPG3970 for oral administration<br>|
| Experimental: GLPG3970 FE<br>Single dose of GLPG3970 in fed and fasted state | Drug: GLPG3970 oral solution<br>* GLPG3970 for oral administration<br>|
| Experimental: GLPG3970 in psoriasis subjects<br> | Drug: GLPG3970 oral solution<br>* GLPG3970 for oral administration<br>|
| Experimental: Placebo in psoriasis subjects<br> | Drug: Placebo oral solution<br>* Placebo for oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment emergent adverse events (TEAEs), treatment-emergent serious adverse events, and TEAEs leading to treatment discontinuations | To evaluate the safety and tolerability of GLPG3970 compared to placebo in adult healthy male subjects as single and multiple ascending oral doses, and in subjects with moderate to severe psoriasis when administered daily for 6 weeks | From screening through study completion, an average of 20 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) of GLPG3970 (Part 1 and 1bis) | To evaluate the pharmacokinetics (PK) of oral SAD of GLPG3970 in adult healthy male subjects | Between Day 1 pre-dose and Day 4 | 
| Maximum observed plasma concentration (Cmax) of GLPG3970 (Part 2) | To evaluate the PK of oral MAD of GLPG3970 in adult healthy male subjects | Between Day 1 pre-dose and Day 17 | 
| Maximum observed plasma concentration (Cmax) of GLPG3970 (Part 3 and 3bis, FE) | To evaluate the food effect on the PK of a single oral dose of GLPG3970 in adult, healthy, subjects | Between Day 1 pre-dose and Day 4 | 
| Maximum observed plasma concentration (Cmax) of GLPG3970 (Part 3, rBA) | To evaluate the PK of a single oral dose of GLPG3970 administered as an oral solution versus and oral capsule in adult, healthy, subjects | Between Day 1 pre-dose and Day 4 | 
| Area under curve (AUC) of GLPG3970 (Part 1 and 1bis) | To evaluate the PK of oral SAD of GLPG3970 in adult healthy male subjects | Between Day 1 pre-dose and Day 4 | 
| Area under curve (AUC) of GLPG3970 (Part 2) | To evaluate the PK of oral MAD of GLPG3970 in adult healthy male subjects | Between Day 1 pre-dose and Day 17 | 
| Area under curve (AUC) of GLPG3970 (Part 3 and 3bis, FE) | To evaluate the food effect on the PK of a single oral dose of GLPG3970 under fed conditions (high-fat high calorie) versus fasted conditions in adult, healthy, subjects | Between Day 1 pre-dose and Day 4 | 
| Area under curve (AUC) of GLPG3970 (Part 3, rBA) | To evaluate the rBA of an oral solution of GLPG3970 versus an oral capsule of GLPG3970 on the PK of a single oral dose of GLPG3970 in adult, healthy, subjects | Between Day 1 pre-dose and Day 4 | 
| Terminal elimination half-life (t1/2) of GLPG3970 (Part 1 and 1bis) | To evaluate the PK of oral SAD of GLPG3970, in adult, healthy, subjects | Between Day 1 pre-dose and Day 4 | 
| Terminal elimination half-life (t1/2) of GLPG3970 (Part 2) | To evaluate the PK of oral MAD of GLPG3970, in adult, healthy, subjects | Between Day 1 pre-dose and Day 17 |