GLP-1 receptor agonist NLY01 to slow brain and retinal atrophy in multiple sclerosis

Targeting Agonists of Glucagon-like Peptide-1 Receptor for Multiple Sclerosis (TAG-MS): A Phase 2, Randomized, Double-Blind, Parallel-Arm Study

This trial will test whether the drug NLY01 can slow brain and retinal shrinkage in adults (18–60) with clinically stable multiple sclerosis who have a BMI of 27 or higher.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: Johns Hopkins University (Academic / other)
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT07497399 on ClinicalTrials.gov

What this trial studies

This is a randomized, placebo-controlled Phase 2 trial comparing NLY01 versus placebo in people with clinically stable multiple sclerosis. The main outcome is change in normalized brain parenchymal volume measured by MRI, with retinal atrophy also monitored as a marker of neurodegeneration. Participants must be on stable MS therapy for at least 12 months and meet metabolic and safety-based eligibility criteria. The trial is conducted at Johns Hopkins and uses imaging endpoints to detect effects on neurodegeneration.

Who should consider this trial

Good fit: Ideal candidates are adults 18–60 with a confirmed diagnosis of MS who are clinically stable on their MS therapy for ≥12 months, have a BMI ≥27 kg/m2, and meet the study's safety criteria.

Not a fit: People with active relapses or new MRI lesions, BMI under 27, pregnancy or planned pregnancy, prior recent GLP‑1/GIP‑GLP‑1 use, or key contraindications (e.g., pancreatitis history, certain thyroid or kidney conditions) are unlikely to benefit or are excluded.

Why it matters

Potential benefit: If successful, NLY01 could slow neurodegeneration and preserve brain volume and vision, potentially delaying disability progression in people with MS.

How similar studies have performed: Preclinical work and early clinical studies in other neurodegenerative diseases suggest GLP‑1 receptor agonists may have neuroprotective effects, but their use specifically for slowing MS-related neurodegeneration is novel and not yet proven in humans.

Eligibility criteria

Inclusion Criteria:

* Diagnosis of MS (2024 criteria); clinically stable on MS therapy for ≥12 months without relapse or new lesions on brain MRI
* Aged 18-60 years
* Body mass index ≥27.0 kg/m2

Exclusion Criteria:

* No GLP-1RA or GIP/GLP-1 RA in past year; no known hypersensitivity to medication class
* No known Barrett's esophagus/gastroesophageal reflux disease, pancreatitis (including past), or gastroparesis
* No personal/family history of medullary thyroid carcinoma or history of multiple endocrine neoplasia syndrome type 2
* No chronic kidney disease (estimated glomerular filtration rate ≤50 mL/min) in past year, type 1 diabetes, known diabetic retinopathy, use of insulin or insulin-inducing medications\*, dipeptidyl peptidase IV inhibitors\*\*, or warfarin; current/active alcohol or illicit substance abuse
* No concerns about candidacy of individual on part of person's neurologist or study team clinicians
* Current or planned (next 2 years) pregnancy/breastfeeding; if able to become pregnant, agree to reliable contraception (contraception requirements as discussed below)\*\*\*

  * currently-approved: Lispro, Aspart, Glulisine, Afrezza, Regular, Concentrated Regular, or Novolin, Velosulin, NPH, glargine, detemir, degludec, and premixed; approved secretagogues: sulphonylureas (e.g. glipizide (± metformin), glyburide (± metformin), glimepiride, pioglitazone/glimepiride) \& meglitinide analogues (nateglinide and repaglinide); \*\* currently-approved:sitagliptin, saxagliptin, linagliptin, alogliptin \*\*\*Contraception: Participants of childbearing potential (participant has a uterus and is pre-menopausal) must agree to use contraception, using either one method with a failure rate of \<1%/year, or two methods of lesser effectiveness:

Contraceptive methods with a failure rate of \< 1% per year includes the following:

* Combined (estrogen and progesterone containing) hormonal contraception (vaginal ring, birth control patch) or progesterone-only hormonal contraception (birth control injections, intrauterine device (IUD), or hormone-releasing implant), or copper IUD
* Complete abstinence from sexual encounters with a person who has testes

Those who do not wish to use one of the above methods of contraception must use two methods. Options include:

* Oral hormonal contraception plus one barrier method during sexual encounter with a person who has testes (below). While typically oral hormonal contraception has a low failure rate, it is possible that the absorption of contraceptive pills taken by mouth will be impacted by the study drug and thus lower contraceptive effectiveness. Thus, people using pills as primary contraception must, during asexual encounter with a person who has testes, use a second form of barrier contraceptive (below) or must change to one of the other contraceptive methods listed above.
* Two forms of barrier contraception during sexual encounter with a person who has testes. Examples of barrier contraceptive methods include the following:

  * A condom with or without spermicide
  * A cap, diaphragm, or sponge with or without spermicide

    * Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

Where this trial is running

Baltimore, Maryland

• Johns Hopkins University — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Ellen M Mowry, MD, MCR — Johns Hopkins University
• Study coordinator: Study Manager

Conditions Multiple Sclerosis