This is a randomized, double-blind, placebo-controlled, stratified, ascending dose, single center study, in three semi-sequential cohorts of 10 male and female subjects of nonchildbearing potential with Osteoarthritis (OA), administered GLPG1972 or placebo. Per cohort, 10 subjects will be randomized in a 4:1 allocation ratio to active treatment with GLPG1972 or matching placebo. In each cohort, OA subjects will be stratified for age (50- 64 years and 65-75 years) with a minimum of 2 of each sex per age group.

Inclusion Criteria:

1. Male or female subjects of non-childbearing potential, 50-75 years of age on the date of signing the Informed Consent Form (ICF), inclusive extremes.
2. Diagnosis of OA (knee and/or hip) made by their physician based on symptoms, clinical signs and documented historical imaging evidence.
3. A body mass index (BMI) between 18.0 and 34.9 kg/m2, inclusive extremes.
4. Judged to be in age-appropriate good health by the investigator based upon the results of a medical history, physical examination, vital signs and 12-lead ECG, and fasting clinical laboratory profile.
5. Subjects with a stable chronic illness at least 3 months will be accepted subject to the investigator's judgment.

Exclusion Criteria:

1. Administration of intraarticular glucocorticoid injections or hyaluronan injections in the last 3 months prior to study screening.
2. Subjects who underwent or are on a waiting list for total hip or knee replacement and any other surgery planned during the study (up to Day 50).
3. Known hypersensitivity to study drug ingredients or a significant allergic reaction to any drug as determined by the investigator, such as anaphylaxis requiring hospitalization.
4. Positive serology for HBsAg or HCV antibody or history of hepatitis from any cause with the exception of hepatitis A.
5. History of or a current immunosuppressive condition.
6. Clinically significant serious, per investigator's discretion, and/or unstable illness in the 3 months before screening
7. Renal function with an estimated creatinine clearance < 60 mL/min based on the Cockcroft-Gault formula. Retesting is allowed once (see Section 5.2).
8. Use of verapamil, diltiazem, amitriptyline, warfarin, acenocoumarol, phenobarbital and phenytoin, within 4 weeks before first study drug administration
9. Consumption of herbal medications that are strong inhibitors and/or inducers of CYPs (e.g., St. John's Wort) and grapefruit/grapefruit products, Seville oranges, or any poppy seed, within 7 days prior to the first study drug administration.
10. History of solid organ or hematopoietic cell transplantation.
11. History of malignancy within the past 5 years.
12. Clinically significant abnormalities detected on 12-lead ECG of either rhythm or conduction (e.g., QTcF ≥ 450 ms for males and QTcF ≥ 470 ms for females, or a known long QT syndrome).
13. Significant blood loss (including blood donation [> 450 mL]), or transfusion of any blood product within 12 weeks prior to screening