Preclinical and clinical evaluation of LY3451838, a PACAP-neutralizing monoclonal antibody, in randomized, double-blind, placebo-controlled phase 1 and phase 2 studies involving healthy adults and adults with treatment-resistant migraine

What Was Tested

The paper reports a study of PACAP in the context of migraine, published as a randomized controlled trial.

AimLY3451838 is a monoclonal antibody against pituitary adenylate cyclase-activating peptide (PACAP), a target in migraine research.

A phase 2 trial was carried out in treatment-resistant participants with chronic migraine (CM) (n = 16) or episodic migraine (EM) (n = 22).

Who Took Part

The abstract describes 2, participants taking part.

By PubMed's age tags, the people studied were young adults, adults and middle-aged adults, both men and women.

How the Study Was Run

In design terms this was a randomized, double-blind and placebo-controlled study.

Random assignment meant chance, not the researchers, decided who got PACAP and who got the comparison, which limits bias.

Blinding on both sides kept the participants and researchers unaware of who received PACAP.

Some participants received a placebo instead of PACAP, giving a reference point.

A time span of 140 days appears in the methods.

What Was Measured

The subject headings attached to it are Migraine Disorders, Pituitary Adenylate Cyclase-Activating Polypeptide, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Monoclonal, Humanized and Drug Evaluation, Preclinical.

The authors tagged it with the keywords PACAP, chronic migraine, episodic migraine, phase 1, phase 2 and treatment-resistant migraine.

What This Means in Plain Language

The paper is a randomized, double-blind and placebo-controlled study of PACAP in 2, participants in people with migraine over 140 days.

With fewer than 40 people, it is a small study, so it is better read as an early signal for further research than as a settled answer.

The publication is from 2025 (Cephalalgia : an international journal of headache), a journal based in England.

More context: the PACAP compound page, Migraine research.