A study to determine how safe and effective ALD403 is in patients with chronic migraine.

Phase 1

Conditions: Chronic Migraine
MedDRA version: 20.0 Level: PT Classification code 10027599 Term: Migraine System Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2016-001306-41-GB

Lead Sponsor: Alder BioPharmaceuticals, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 1121

Inclusion Criteria

1.Willing and able to read, understand, and sign the Informed Consent Form (ICF) for the clinical trial approved by the Investigator’s local Review Board or a central Institutional Review Board (IRB) or Ethics Committee (EC).
2.Has adequate venous access for administration of investigational product and collection of blood samples.
3.Male or female 18-65 years of age, inclusive, at time of informed consent.
4.Diagnosis of migraine at = 50 years of age with history of chronic migraine = 1 year prior to screening.
5.Prescription or over-the-counter medication for acute and/or prophylactic treatment of migraine has been prescribed or recommended by a healthcare professional.
6.During the 28 day screening period, must have = 15 to = 26 headache days, of which = 8 days were assessed as migraine days as documented in the eDiary (ICHD-III beta
version, 2013 Section 1.3).
7.Women of child-bearing potential, and males with partners of child-bearing potential, must agree to use adequate contraception for the duration of the study (from screening through Week 32) and for 6 months after the last dose of study drug. The following types of contraception are considered adequate provided they are locally authorised for use: oral, transdermal, or injectable (depot) estrogen and/or progestogen, selective estrogen receptor modulator therapy, intrauterine contraceptive device, double barrier method (e.g., condom and diaphragm or spermicidal gel) or vasectomy. Non-childbearing potential is defined as post-menopausal for at least 1 year, or surgical sterilization or hysterectomy at least 3 months before screening.
8.Any hormonal therapy (e.g., contraceptives, hormone replacement therapy) use is stable and ongoing for at least 3 months prior to screening .
9.Willing, committed, and able to comply with scheduled clinic visits and complete all trial-related procedures.
10.Headache eDiary was completed on at least 24 of the 28 days prior to randomization.
11.Any prophylactic use of medications for headaches must be stable for at least 3 months prior to screening.
12.Limited use of barbiturates (including Fiorinal®, Fioricet®, or any other combination containing butalbital) or prescription opiates ( including single ingredient or combinations containing opiates, opioids, tramadol or tapentadol) by maintaining a stable dose for 2 months prior to screening and dosing is not expected to exceed 4 days per month through Week 24.
13.Subject agrees not to post any personal medical data or information related to the trial
on any website or social media site (e.g., Facebook, Twitter) during the trial.
14.Subject is willing to complete the daily eDiary for the duration of the study and agrees to use the eDiary devices for the sole purpose of the ALD403-CLIN-011 study without alteration.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1040
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1.Confounding and clinically significant pain syndromes (e.g. fibromyalgia, chronic low back pain, complex
regional pain syndrome).
2.Psychiatric conditions that are uncontrolled and/or untreated, including conditions that are not controlled for a minimum of 6 months prior to screening. Patients with a lifetime history of psychosis, mania, or dementia are excluded.
3.Diagnosis of acute or active temporomandibular disorders (TMD).
4.History or diagnosis of chronic tension-type headache, hypnic headache, cluster headache, hemicrania continua, new daily persistent headache, or unusual migraine subtypes such as hemiplegic migraine (sporadic and familial), opthalmoplegic migraine and migraine with neurological accompaniments that are not typical of migraine aura (eg. diplopia, altered consciousness or long duration).
5.Any use of approved devices, neuromodulation, neurostimulation or injectable therapy (trigger point injections, extracranial nerve blocks, facet joint injections) are prohibited 2 months prior to screening and during the screening period.
6.Any use of botulinum toxin for migraine or for any other medical/cosmetic reasons requiring injections within 4 months prior to screening and during the screening period.
7.Any use of monoamine oxidase inhibitors (MAOIs), ketamine, methysergide,
methylergonovine, or nimesulide within 3 months prior to screening or during the
screening period.
8.Have present or previous malignancies, except:
Squamous or basal skin cell carcinoma with excision without evidence of
recurrence
Malignancy = 10 years since diagnosis/treatment without evidence of recurrence
9.Subject with known history or evidence of arteriosclerosis,cardiomyopathy, coronary artery disease, serious heart rhythm abnormalities, cerebrovascular disease, diabetes, Raynaud’s disease, hereditary fructose intolerance, lifethreatening allergy (e.g, anaphylaxis) or any active, progressive or unstable cardiovascular, neurological or autoimmune disorder. If questions arise, the Investigator should contact the Medical Monitor for guidance.
10.Clinically significant abnormal ECG during the screening period or on Day 0.
11.Any clinically significant concurrent medical condition or clinically significant
laboratory abnormality during the screening period or on Day 0.
12.Body Mass Index (BMI) = 39 kg/m2 at screening.
13.Primary hypertension that is uncontrolled or newly diagnosed (systolic BP of > 139 mm Hg or diastolic BP of >89 mm Hg) at screening or secondary hypertension. Mild primary hypertension that is well-controlled for = 6 months prior to screening is allowed.
14.The subject is at risk of self-harm or harm to others in the Investigator’s opinion, based on clinical interview and responses provided on the Columbia-Suicide Severity Rating Scale (C-SSRS). Subjects must be excluded if they have a lifetime history of a serious suicide attempt or multiple suicide attempts (i.e., actual, interrupted, or aborted attempts), have had any suicidal behavior in the past 5 years (i.e., preparatory acts or behavior), or have had suicidal ideation of Type 3, 4, or 5 (i.e., suicidal ideation with any me

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of repeat doses of ALD403 administered intravenously (IV) compared to placebo in patients with chronic migraine.;Primary end point(s): Change in frequency of migraine days ;Timepoint(s) of evaluation of this end point: Weeks 1-12;<br> Secondary Objective: To evaluate the safety of repeat doses of ALD403 administered IV compared to placebo in patients with chronic migraine.<br> To evaluate the pharmacokinetics (PK) and immunogenicity of repeat doses of ALD403 administered IV to patients with chronic migraine.<br>

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): 75% migraine responder rate<br> 50% migraine responder rate<br> Percentage of subjects with a migraine on the day after dosing<br> Reduction in migraine prevalence from baseline to Week 4<br> ;Timepoint(s) of evaluation of this end point: Weeks 1-4 and Weeks 1-12