Effect of RANKL Inhibition on UV-induced Immunosuppression

Inclusion criteria

• 1. Men or postmenopausal women 18 years of age or older at time of consent.
• 2. Male subject or his female partner (this criterion does not apply to post-menopausal female) is willing to use effective contraceptive method for at least 30 days before Day 0 and at least 1 month after the last study drug administration. Effective contraceptive methods are:

• Barrier methods such as condom, sponge or diaphragm combined with spermicide in foam, gel or cream;
• Hormonal contraception (oral, intramuscular, implant or transdermal) which include Depo-Provera, Evra and Nuvaring;
• Intrauterine device (IUD);
• Sterilization such as tubal ligation, hysterectomy or vasectomy;
• Postmenopausal state for at least 1 year for female subject or female partner of male subject;
• Same-sex partner;
• Abstinence.
• 3. Capable of giving informed consent and the consent must be obtained prior to any study related procedures.
• 4. Fitzpatrick skin phototypes II or III.
• 5. Subject weighs 100kg or less.

Exclusion criteria

• 1. Conditions or medications causing immunosuppression, photosensitization or phototoxicity.
• 2. Past history of skin cancer or subject having precancerous skin lesions (eg. actinic keratosis).
• 3. Subject has atopic dermatitis (cohort 1)
• 4. Subject has received investigational drugs within the 28 days or 5 half-lives, whichever is longer, prior to Day 0 or plans to during the study period.
• 5. Subject has used any topical medication on arms or buttocks within 14 days of Day 0 or plans to during the study.
• 6. At the investigator's discretion subject has current or past history of alcohol or drug abuse that would interfere with the ability of the subject to comply with the study protocol.
• 7. Hypersensitivity/allergy to denosumab.
• 8. Hypersensitivity/allergy to lidocaine.
• 9. Hypersensitivity/allergy to latex.
• 10. Subject is taking anticoagulant medication except for low dose acetylsalicylic acid.
• 11. Past history of hypocalcemia or predisposing factors (eg, history of hypoparathyroidism, thyroid surgery, parathyroid surgery, malabsorption syndromes, excision of small intestine, severe renal impairment or receiving dialysis).
• 12. Known vitamin D deficiency.
• 13. Creatinine clearance less than 30mL/min (Cohort 2 only).
• 14. Corrected calcium concentration inferior to the normal range (Cohort 2 only).
• 15. Past history of osteonecrosis of the jaw (ONJ) or risk factors for ONJ (poor oral hygiene, periodontal and/or pre-existing dental disease, diagnosis of cancer with bone lesions, invasive dental procedures such as dental extractions or implants within 6 months of the screening visit.)
• 16. Past history of keloids or hypertrophic scarring.
• 17. Prior treatment with diphenylcyclopropenone.
• 18. Treatment with denosumab in the past 12 months.
• 19. Significant limitations in the range of motion of arms or shoulders.