i-NEED: NEw migrainE Drugs Database

NCT07103694 | Recruiting

• 1 other identifier: RP 22/02
• Study Type: observational
• Target: 2,641
• Locations: 1 country
• Sites: 1

Brief Summary

Approved by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) starting in 2018, anti-CGRP monoclonal antibodies (anti-CGRP mAbs) represent the first true revolution in the preventive treatment of migraine due to their selectivity and specificity. To date, four anti-CGRP mAbs have been developed for the preventive treatment of migraine: eptinezumab, erenumab, fremanezumab, and galcanezumab.Anti-CGRP mAbs constitute not only the first specific and selective treatment for the prevention of migraine but also the most extensively studied pharmacological category in this field, considering the vast and complex populations examined. The clinical effects of the various mAbs are substantially comparable and are characterized by several fundamental aspects:

• High efficacy in both episodic and chronic migraine, with the presence of super-responders who experience a reduction in the average monthly number of migraine days of \>75% (or even 100%) compared to before treatment.
• Efficacy that is independent of the clinical form of migraine - with or without aura - and regardless of whether there is analgesic overuse.
• Efficacy maintained even in the presence of depressive or anxious comorbidities.
• Rapid onset of action (even more pronounced with eptinezumab), with the therapeutic effect appearing within the first week in most cases.
• Excellent tolerability with an absence of class-specific adverse events.
• Outstanding treatment adherence and a very low rate of treatment discontinuation in the long term. It should also be noted that the development of anti-drug antibodies or neutralizing antibodies to anti-CGRP mAbs is rare and does not significantly impact the efficacy or tolerability of treatment. Future clinical practice will need to clarify several additional aspects, such as: 1) whether treatment with anti-CGRP mAbs can modify the course of migraine; 2) the appropriate approach regarding any traditional preventive treatment (whether to continue or discontinue it); 3) the definition of the characteristics of non-responders; 4) the definition of patients with a delayed response to treatment. Gepants are oral antagonists of the CGRP receptor. Among the four gepants synthesized so far (atogepant, rimegepant, ubrogepant, zavegepant), atogepant and rimegepant are currently available in Italy. Atogepant has proven to be an effective and well-tolerated option for the prevention of episodic and chronic migraines. Rimegepant is effective for both acute treatment and prevention of migraines, with a favorable safety profile and flexible oral administration. Lasmiditan is the first ditan effective for migraine attack and it represents a new therapeutic option for patients with contraindications to triptans, due to the presence of vascular risk factors, or for patients who experience undesirable side effects with these, thus increasing the therapeutic possibilities for the symptomatic treatment of migraine. The combination of sumatriptan 85 mg and naproxen sodium 500 mg is indicated for the acute treatment of migraine attacks in adult patients for whom sumatriptan monotherapy is insufficient.

Conditions

Episodic Migraine; Chronic Migraine; Medication Overuse Headache

Keywords

migraine, anti-CGRP monoclonal antobodies, gepants, ditans, sumatriptan and naproxen combination

Outcome Measures

Primary Outcomes (6)

• effectiveness of innovative drugs as migraine prophylaxis

  reduction in the number of monthly migraine days compared to the baseline average recorded in the three months preceding treatment

  the assessment will be conducted at 4 weeks from treatment initiation

• effectiveness of innovative drugs as migraine prophylaxis

  reduction in the number of monthly migraine days compared to the baseline average recorded in the three months preceding treatment

  the assessment will be conducted at 8 weeks from treatment initiation

• effectiveness of innovative drug as migraine prophylaxis

  reduction in the number of monthly migraine days compared to the baseline average recorded in the three months preceding treatment

  the assessment will be conducted at 12 weeks from treatment initiation

• effectiveness of innovative drugs as migraine prophylaxis

  reduction in the number of monthly migraine days compared to the baseline average recorded in the three months preceding treatment

  the assessment will be conducted at 24 weeks from treatment initiation

• effectiveness of innovative drugs as migraine prophylaxis

  reduction in the number of monthly migraine days compared to the baseline average recorded in the three months preceding treatment

  the assessment will be conducted at 48 weeks from treatment initiation

• 2 hour-pain freedom

  Percentage of patients reporting complete pain relief within 2 hours after taking the innovative drug for migraine attack

  2 hours

Secondary Outcomes (55)

• safety and tolerability of innovative drugs as migraine prophylaxis

  the assessment will be conducted at 48 weeks from treatment initiation

• impact of innovative drugs as migraine prophylaxis on symptomatic medication use and medication overuse headache

  the assessment will be conducted at 48 weeks from treatment initiation

• impact of innovative drugs as migraine prophylaxis on migraine symptoms

  the assessment will be conducted at 4 weeks from treatment initiation

• impact of innovative drugs as migraine prophylaxis on migraine symptoms

  the assessment will be conducted at 8 weeks from treatment initiation

• impact of innovative drugs as migraine prophylaxis on migraine symptoms

  the assessment will be conducted at 12 weeks from treatment initiation

Study Arms (1)

individuals affected by migraine

episodic and chronic migraine

Drug: anti-CGRP monoclonal antibodies; Drug: gepants; Drug: combination of sumatriptan and naproxen; Drug: ditan

Interventions

anti-CGRP monoclonal antibodies DRUG

erenumab, fremanezumab, galcanezumab, eptinezumab

individuals affected by migraine

gepants DRUG

atogepant, rimegepant

individuals affected by migraine

combination of sumatriptan and naproxen DRUG

combination of sumatriptan and naproxen

individuals affected by migraine

ditan DRUG

lasmiditan

individuals affected by migraine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Eligible patients include * adults (equal or more 18 years) * episodic or chronic migraine diagnosis, * treated with preventive or acute treatment drugs

You may qualify if:

• Age more or equal 18 years;
• Males and females;
• Willingness to sign the informed consent;
• Episodic migraine for the use of drug indicated for migraine attack
• High frequency episodic migraine, at least 8 days per month of disabling migraine in the past 3 months;
• Chronic migraine, according to the ICHD-III criteria;

You may not qualify if:

• Other headaches different than migraine;
• Known intolerance to the eccipients;
• Vascular disease or Raynaud.

Sponsors & Collaborators

• IRCCS San Raffaele Roma: lead

Study Sites (1)

IRCCS San Raffaele

Rome, Italy, 00163, Italy

RECRUITING

Related Publications (12)

• Sacco S, Bendtsen L, Ashina M, Reuter U, Terwindt G, Mitsikostas DD, Martelletti P. European headache federation guideline on the use of monoclonal antibodies acting on the calcitonin gene related peptide or its receptor for migraine prevention. J Headache Pain. 2019 Jan 16;20(1):6. doi: 10.1186/s10194-018-0955-y.

  PMID: 30651064 BACKGROUND

• Goadsby PJ, Reuter U, Hallstrom Y, Broessner G, Bonner JH, Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA. A Controlled Trial of Erenumab for Episodic Migraine. N Engl J Med. 2017 Nov 30;377(22):2123-2132. doi: 10.1056/NEJMoa1705848.

  PMID: 29171821 BACKGROUND

• Reuter U, Goadsby PJ, Lanteri-Minet M, Wen S, Hours-Zesiger P, Ferrari MD, Klatt J. Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. Lancet. 2018 Nov 24;392(10161):2280-2287. doi: 10.1016/S0140-6736(18)32534-0. Epub 2018 Oct 22.

  PMID: 30360965 BACKGROUND

• Stauffer VL, Dodick DW, Zhang Q, Carter JN, Ailani J, Conley RR. Evaluation of Galcanezumab for the Prevention of Episodic Migraine: The EVOLVE-1 Randomized Clinical Trial. JAMA Neurol. 2018 Sep 1;75(9):1080-1088. doi: 10.1001/jamaneurol.2018.1212.

  PMID: 29813147 BACKGROUND

• Detke HC, Goadsby PJ, Wang S, Friedman DI, Selzler KJ, Aurora SK. Galcanezumab in chronic migraine: The randomized, double-blind, placebo-controlled REGAIN study. Neurology. 2018 Dec 11;91(24):e2211-e2221. doi: 10.1212/WNL.0000000000006640. Epub 2018 Nov 16.

  PMID: 30446596 BACKGROUND

• Dodick DW, Silberstein SD, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, Grozinski-Wolff M, Yang R, Ma Y, Aycardi E. Effect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine: A Randomized Clinical Trial. JAMA. 2018 May 15;319(19):1999-2008. doi: 10.1001/jama.2018.4853.

  PMID: 29800211 BACKGROUND

• Silberstein SD, Dodick DW, Bigal ME, Yeung PP, Goadsby PJ, Blankenbiller T, Grozinski-Wolff M, Yang R, Ma Y, Aycardi E. Fremanezumab for the Preventive Treatment of Chronic Migraine. N Engl J Med. 2017 Nov 30;377(22):2113-2122. doi: 10.1056/NEJMoa1709038.

  PMID: 29171818 BACKGROUND

• Dodick DW, Goadsby PJ, Silberstein SD, Lipton RB, Olesen J, Ashina M, Wilks K, Kudrow D, Kroll R, Kohrman B, Bargar R, Hirman J, Smith J; ALD403 study investigators. Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomised, double-blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol. 2014 Nov;13(11):1100-1107. doi: 10.1016/S1474-4422(14)70209-1. Epub 2014 Oct 5.

  PMID: 25297013 BACKGROUND

• Lipton RB, Goadsby PJ, Smith J, Schaeffler BA, Biondi DM, Hirman J, Pederson S, Allan B, Cady R. Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2. Neurology. 2020 Mar 31;94(13):e1365-e1377. doi: 10.1212/WNL.0000000000009169. Epub 2020 Mar 24.

  PMID: 32209650 BACKGROUND

• Lipton RB, Croop R, Stock EG, Stock DA, Morris BA, Frost M, Dubowchik GM, Conway CM, Coric V, Goadsby PJ. Rimegepant, an Oral Calcitonin Gene-Related Peptide Receptor Antagonist, for Migraine. N Engl J Med. 2019 Jul 11;381(2):142-149. doi: 10.1056/NEJMoa1811090.

  PMID: 31291516 BACKGROUND

• Goadsby PJ, Wietecha LA, Dennehy EB, Kuca B, Case MG, Aurora SK, Gaul C. Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine. Brain. 2019 Jul 1;142(7):1894-1904. doi: 10.1093/brain/awz134.

  PMID: 31132795 BACKGROUND

• Brandes JL, Kudrow D, Stark SR, O'Carroll CP, Adelman JU, O'Donnell FJ, Alexander WJ, Spruill SE, Barrett PS, Lener SE. Sumatriptan-naproxen for acute treatment of migraine: a randomized trial. JAMA. 2007 Apr 4;297(13):1443-54. doi: 10.1001/jama.297.13.1443.

  PMID: 17405970 BACKGROUND

MeSH Terms

Conditions

Headache Disorders, Secondary; Migraine Disorders

Interventions

Calcitonin Gene-Related Peptide Receptor Antagonists; Naproxen

Condition Hierarchy (Ancestors)

Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Central Nervous System Agents; Therapeutic Uses; Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Central Study Contacts

Piero Barbanti, MD, PhD

CONTACT

+390652254318; piero.barbanti@sanraffaele.it

Cinzia Aurilia

CONTACT

+390652254318; cinzia.aurilia@sanraffaele.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2025
• First Posted: August 5, 2025
• Study Start: March 24, 2022
• Primary Completion: December 30, 2025
• Study Completion: December 31, 2025
• Last Updated: August 5, 2025

Record last verified: 2025-08

Locations

IT (1)