Effect of RANKL Inhibition on UV-induced Immunosuppression

This is an interventional basic science trial for Ultraviolet Rays focused on measuring Humans, Adult, skin, metabolism, radiation effects, Ultraviolet Rays, RANKL, RANK Ligand, denosumab, diphenylcyclopropenone, diphencyprone, immunology, immunosuppression, Antibodies, Monoclonal, Dermatitis, Allergic Contact, Hypersensitivity, Delayed Read More

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:

  1. Barrier methods such as condom, sponge or diaphragm combined with spermicide in foam, gel or cream;
  2. Hormonal contraception (oral, intramuscular, implant or transdermal) which include Depo-Provera, Evra and Nuvaring;
  3. Intrauterine device (IUD);
  4. Sterilization such as tubal ligation, hysterectomy or vasectomy;
  5. Postmenopausal state for at least 1 year for female subject or female partner of male subject;
  6. Same-sex partner;
  7. 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.