A Study of CGRP Monoclonal Antibody to Treat Diabetic Neuropathy

Inclusion Criteria:

• Confirmed diagnosis of probable diabetic polyneuropathy, as defined by the Torontoconsensus criteria and a TCNS > 5 or abnormal DPNCheck or abnormal NCS.

• Probable neuropathic pain as defined by the NeuPSIG guidelines.

• Symmetric distal pain worse in the distal lower extremities present for > 6 months.

• Average pain score on a NRS of ≥ 4 during the baseline week.

Exclusion Criteria:

• Prior or current use of a CGRP mAbs or CGRP antagonists.

• Opioid regimen other than stable low dose of Tramadol (maximum 200 mg/day).

• The patient has a lifetime history of psychosis, bipolar mania, or dementia.Patients with other psychiatric conditions whose symptoms are not controlled or whohave not been adequately treated for a minimum of 6 months prior to screening arealso excluded.

• Initiation of new neuropathic pain medications such as gabapentinoid medications (gabapentin, pregabalin) and/or capsaicin (Quetenza), botulinum toxin type A,serotonin/norepinephrine reuptake inhibitors (TCA or duloxetine or venlafaxine) 1month prior to enrollment or for the duration of the randomized placebo-controlledphase of the study. Current and ongoing pain treatment will be allowed in stabledose (anticonvulsants, antidepressants, tramadol, topical treatments (excluding highdose capsaicin patch and botulinum toxin type A) (Paracetamol 1g andover-the-counter NSAIDS as needed up to four times daily are allowed as rescuemedicine).

• Suspected cause of lower extremity pain of other causes than diabetes (e.g.,chemotherapy, alcohol or drug misuse, vitamin deficiency, concomitant centralnervous system pathology) or patients with pain that cannot be distinguished fromtheir neuropathic pain in the feet due to diabetes.

• The patient has a history of clinically significant cardiovascular disease,including uncontrolled hypertension, ischaemia or thromboembolic events (forexample, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism).

• The patient has a BMI ≥ 39 kg/m^2 at the screening visit.

• Peripheral arterial disease (PAD) defined as toe pressure < 40mmHg, no palpable footpulses or clinical claudicatio intermittens.

• Chronic wounds.

• Planned larger surgery in the treatment period.

• Unable to understand Danish (Danish site only).

• All female subjects of childbearing potential must have negative result of a serumpregnancy test performed at screening. Subjects of childbearing potential must agreeto use a medically approved form of birth control (abstinence, intrauterine device (IUD), oral contraception, barrier and spermicide or hormonal implant) throughoutthe duration of the study.