CALM-AF-AI: Counteracting Age-related Loss of Muscle With AAV-Follistatin Combined With Angiogenesis-Inducing VEGF Plasmid Gene Therapy

What Was Tested

This registered phase 1, phase 2 trial tested Follistatin-344.

This Phase 1/2a, open-label, non-randomized study is designed to evaluate the safety and tolerability of intramuscular AAV9-Follistatin gene therapy administered either as monotherapy or in combination with a VEGF-encoding plasmid.

Secondary objectives include the assessment of preliminary signals of biological and functional activity, including changes in skeletal muscle mass and performance.

It had three arms (groups): one (experimental), one (experimental) and Combination: AAV-Follistatin + VEGF Plasmid (experimental).

The registry classes the interventions as genetic.

More on the Plan

All investigational products are administered via intramuscular injection into large skeletal muscles.

In Cohorts 1 and 2, AAV-Follistatin is administered once on Day 1.

Rapamycin will be administered for approximately two months to mitigate immune responses to the AAV vector.

Participants will undergo regular safety monitoring, including clinical assessments, laboratory testing, and strength evaluations.

Who Took Part

12 planned participants were the target.

It was open to people of any sex aged from 35 years up to 75 years.

Healthy volunteers could join, not only people with the condition.

Examples of who could join: Voluntary written informed consent obtained prior to any study-related procedures. Ability to read, understand, and sign the Informed Consent Form and reliably complete required study documents. Willingness to undergo medical intervention, including genetic therapy, and to comply with the visit schedule and all study procedures. Commitment to maintain a stable medication and supplement regimen throughout the study, with no initiation of new medications, supplements, or performance-enhancing substances unless approved by the Investigator. Men and women aged 35-75 years.

The full record lists 11 inclusion and 80 exclusion criteria; among the exclusions: subjects who have a history of alcohol or drug abuse within 1 year of study entry; active malignancy or any history of cancer; any history of stroke, transient ischemic attack (tia), myocardial infarction (mi), or unstable angina (regardless of time since event).

How the Study Was Run

The set-up was non-randomized, sequential and open-label.

Nothing was hidden in this open-label Follistatin-344 study: the participants and staff both knew the treatment.

It started in 2026-06-01 with completion listed for 2027-09-30.

It ran at 1 site in Honduras.

Its stated primary purpose is prevention.

What Was Measured

The main thing measured (primary outcome): Number of participants with treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) (time frame: Day 1 through Day 90 after AAV administration).

It also tracked 4 secondary outcomes, for example Number of participants with new-onset symptomatic heart failure or arrhythmias (CTCAE Grade ≥2), Number of participants with injection site reactions and Number of participants who discontinue study treatment due to adverse events.

What This Means in Plain Language

Put simply, this is a phase 1, phase 2, non-randomized trial of Follistatin-344 in 12 people.

Its size is small, so on its own it can only give an early look.

It is still recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Follistatin-344 compound page, all human trials.