Study to Evaluate the Efficacy and Safety of Lenalidomide in the Treatment of Complex Regional Pain Syndrome Type 1

A Multicenter, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Lenalidomide in the Treatment of Complex Regional Pain Syndrome Type 1

The purpose of this multicenter, double-blind, placebo-controlled study is to evaluate the efficacy and safety of Lenalidomide in adult subjects with Complex Regional Pain Syndrome (CRPS) Type 1.

This is a multicenter, double-blind, placebo-controlled study in adult subjects with Complex Regional Pain Syndrome (CRPS) Type 1.

One hundred eighty (180) subjects diagnosed with unilateral CRPS Type 1 will be enrolled and randomized to receive orally either 10 mg/day of lenalidomide or placebo (90 subjects per treatment arm). For each subject, the study consists of three phases: Pre-randomization Phase (2 weeks), Treatment Phase (12 weeks) and Extension Phase where subjects have the opportunity to receive lenalidomide treatment as long as a benefit is derived from the drug. Subjects who complete all 12 weeks of the treatment phase may be eligible to receive lenalidomide in the extension phase. Subject may continue in the extension phase as long as a benefit is derived from the drug.

Inclusion Criteria:

• Age >= 18 years at the time of signing the informed consent form
• Understand and voluntarily sign an informed consent form
• A diagnosis of CRPS Type 1, as defined by modified International Association for the Study of Pain criteria for at least a one-year duration. Unilateral involvement of a distal limb (hand or foot) with or without proximal spread must be present. In the presence of upper and lower limb involvement, the most severely affected limb will be designated the CRPS-affected limb.
• Screening: CRPS pain intensity score in the CRPS-affected limb must be at least 4 on an 11-point (0-10) Pain Intensity Numerical Rating Scale (PI-NRS).
• Randomization: Average PI-NRS score for randomization purposes will be based on AM and PM assessments made during the 7 days prior to randomization. At least eight PI-NRS scores during this 7-day period are required and the Average PI-NRS score in the CRPS-affected limb during this period must be at least 4 on an 11-point (0-10) PI-NRS.
• Measurable (by electrophysiology methods) sural, median sensory, median motor and peroneal motor nerves at the screening nerve conduction study.
• Opioid analgesics, non-opioid analgesics, non-steroidal anti-inflammatory drugs, anticonvulsants, antidepressant drugs and other non-drug therapies may be continued provided that the subject is on stable doses/regimens for at least four weeks prior to the start of the Treatment Phase (Visit 2).
• Able to adhere to the study visit schedule and other protocol requirements.
• Women of childbearing potential (WCBP) must agree to practice complete abstinence from heterosexual intercourse or to use two methods of contraception beginning 4 weeks prior to the start of study drug (Day 1) while on study drug (including dose interruptions) and 4 weeks after the last dose of study drug. The two methods of contraception must include one highly effective method (i.e. intrauterine device [IUD], hormonal [birth control pills, injections, or implants only if used in conjunction with a low-dose (81 mg/day) aspirin regimen], tubal ligation, partner's vasectomy) and one additional effective (barrier) method (i.e. latex condom, diaphragm, cervical cap). If a hormonal method (birth control pills, injections, or implants) or IUD is not medically possible for the subject, two of the barrier methods will be acceptable.
• Women of childbearing potential (WCBP) must have two negative pregnancy tests (sensitivity of at least 50 mlU/mL) prior to starting study drug treatment. The first test should be performed within 10-14 days and the second within 24 hours of starting study drug. Once treatment has started, it is recommended that subjects have weekly pregnancy test during the first 4 weeks of treatment. Thereafter, subjects are required to have pregnancy testing every 4 weeks in females with regular menstrual cycles and every 2 weeks in females with irregular cycles.
• Males (including those who have had a vasectomy) must use barrier contraception (latex condoms) when engaging in reproductive sexual activity with WCBP while on study drug and for 4 weeks after the last dose of study drug.

Exclusion Criteria:

The presence of any of the following will exclude a subject from study enrollment:

• History of deep vein thrombosis (DVT) or stroke in the past 5 years.
• Documented peripheral neuropathies to include diabetic neuropathy and other metabolic or toxic neuropathies.
• Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, neurological or cerebral disease.
• Any other serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• White blood cell count (WBC) < 3.5*10^9/L at screening.
• Bilirubin, alanine transaminase (ALT), aspartate transaminase (AST) or alkaline phosphatase levels more than two times the upper limit of the normal range at screening.
• Abnormal thyroid function test values at screening.
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
• Use of concomitant medication(s), which could increase the risk for developing DVT, except for steroid-based contraceptives (oral injectable, implantable) and hormone replacement therapies only if used in conjunction with a low-dose (81 mg/day) aspirin regimen.
• Concurrent use of thalidomide.
• Prior development of an allergic reaction/hypersensitivity while taking thalidomide.
• Prior development of a moderate or severe rash or any desquamation while taking thalidomide.
• Prior treatment with lenalidomide.