E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027599 |
E.1.2 | Term | Migraine |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of repeat doses of ALD403 administered intravenously (IV) compared to placebo in patients with chronic migraine. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the safety of repeat doses of ALD403 administered IV compared to placebo in patients with chronic migraine.
To evaluate the pharmacokinetics (PK) and immunogenicity of repeat doses of ALD403 administered IV to patients with chronic migraine. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 authorized 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 and through Week 32.
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. |
|
E.4 | Principal 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), ophthalmoplegic
migraine and migraine with neurological accompaniments that are not typical of migraine aura (e.g., 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 witha known history or evidence of arteriosclerosis, cardiomyopathy, coronary artery disease, serious heart rhythm abnormalities, neurological disease, 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 method without intent to act or suicidal ideation with intent to act, with or without a plan) in the past 6 months, as measured by the C-SSRS at Screening or on Day 0.
15.Any history or evidence of substance abuse or dependence (e.g., alcohol, opiates, amphetamines and barbiturates) within the past 2 years according to the International Classification of Diseases (ICD) 10: F10-1912
16.Pregnant, breastfeeding, or planning to become pregnant during the trial.
17.Receipt of any experimental, unregistered therapy (within or outside a clinical trial) within 30 days or 5 plasma half-lives (whichever is longer) before screening.
18.Receipt of any monoclonal antibody treatment (within or outside a clinical trial) within 6 months before screening.
19.Previously dosed with ALD403 or any monoclonal antibody targeting the CGRP
pathway.
20.Planned or current participation in any other clinical trial during the duration of this clinical trial, or within 6 months before screening.
21.Recent or planned surgery, requiring general anesthesia, within 8 weeks prior to screening and during the duration of this clinical trial.
22.Positive for HIV, hepatitis B surface antigen, or hepatitis C antibody at screening.
23.Any condition that, in the opinion of the Investigator, would make the subject
unsuitable for the clinical trial.
24.Employees of the Sponsor, CRO, or any clinical trial site involved in this trial and their immediate family members (i.e., parents, spouse, siblings, children). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change in frequency of migraine days |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• 75% migraine responder rate (Weeks 1-4)
• 75% migraine responder rate (Weeks 1-12)
• 50% migraine responder rate (Weeks 1-12)
• Percentage of subjects with a migraine on the day after dosing
• Reduction in migraine prevalence from baseline to Week 4
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Czech Republic |
Denmark |
Georgia |
Germany |
Hungary |
Italy |
Russian Federation |
Slovakia |
Spain |
Ukraine |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 15 |