i-NEED: NEw migrainE Drugs Database

NCT ID: NCT07103694

Last Updated: 2025-08-05

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 2641 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-03-24
• Study Completion Date: 2025-12-31

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.

Detailed Description

The European Headache Federation has published detailed guidelines on the state of the art regarding evidence of effectiveness in reducing the frequency and intensity of headache episodes, as well as the safety and tolerability of the four monoclonal antibodies under "ideal" experimental conditions, with patients selected based on stringent inclusion and exclusion criteria. This selection limits the direct transferability of the conclusions of these studies to clinical reality. Therefore, this study aims to evaluate, in a clinical practice setting, the real effectiveness in reducing the monthly frequency of migraine days and the tolerability and efficacy of monoclonal antibodies in a real-world evidence context. The study may later include all drugs that become available for this condition, subject to authorization by the competent Italian authority.

The present extension of the I-NEED study aims to integrate the collection and evaluation of real-life data on anti-CGRP monoclonal antibodies for migraine prophylaxis with the study of efficacy, safety, and tolerability-also in a real-world evidence context-of gepants in the prophylaxis of episodic and chronic migraine, and of rimegepant, ditans, and the sumatriptan-naproxen combination in the acute treatment of migraine.

Conditions

Episodic Migraine; Chronic Migraine; Medication Overuse Headache

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

individuals affected by migraine

episodic and chronic migraine

anti-CGRP monoclonal antibodies

Intervention Type: DRUG

erenumab, fremanezumab, galcanezumab, eptinezumab

gepants

Intervention Type: DRUG

atogepant, rimegepant

combination of sumatriptan and naproxen

Intervention Type: DRUG

combination of sumatriptan and naproxen

ditan

Intervention Type: DRUG

lasmiditan

Interventions

anti-CGRP monoclonal antibodies

erenumab, fremanezumab, galcanezumab, eptinezumab

Intervention Type: DRUG

gepants

atogepant, rimegepant

Intervention Type: DRUG

combination of sumatriptan and naproxen

combination of sumatriptan and naproxen

Intervention Type: DRUG

ditan

lasmiditan

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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;

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IRCCS San Raffaele Roma

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

IRCCS San Raffaele

Rome, Italy, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Piero Barbanti, MD, PhD

Role: CONTACT

piero.barbanti@sanraffaele.it

+390652254318

Cinzia Aurilia

Role: CONTACT

cinzia.aurilia@sanraffaele.it

+390652254318

Facility Contacts

Piero Barbanti, MD, PhD

Role: primary

piero.barbanti@sanraffaele.it

+390652254318

Cinzia Aurilia, MD

Role: backup

cinzia.aurilia@sanraffaele.it

+390652254318

References

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Reference Type: BACKGROUND

PMID: 30651064 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 29171821 (View on PubMed)

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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

PMID: 29813147 (View on PubMed)

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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

PMID: 29800211 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 29171818 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25297013 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32209650 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31291516 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31132795 (View on PubMed)

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.

Reference Type: BACKGROUND

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Other Identifiers

RP 22/02

Identifier Type: -

Identifier Source: org_study_id