Targeting Agonists of Glucagon-like Peptide-1 Receptor for Multiple Sclerosis (TAG-MS)

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

The goal of this clinical trial is to evaluate if the study drug will reduce brain and retinal atrophy by reducing inflammation and subsequently slowing neurodegeneration in people with Multiple Sclerosis. The main outcome for the trial is change in normalized brain parenchymal volume (nBPV), measured by magnetic resonance imaging (MRI).

Researchers will compare outcomes from participants randomized to the study drug, versus participants randomized to placebo, to see if there are signs of slowed neurodegeneration (i.e., reduction in brain and retinal atrophy).

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: NLY01; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Study Manager; Phone Number: 667-306-8153; Email: mvieira4@jh.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins University
      • Principal Investigator: Ellen Mowry, MD, MCR
      • Contact: Margaret Vieira; Phone Number: 667-306-8153; Email: mvieira4@jh.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo (saline solution)
Active Comparator: NLY01 (Study Drug); 5 mg subcutaneous weekly for the first 4 weeks, then 10 mg subcutaneous weekly, with pre-planned dose adjustments if adverse events prevent full dosage.	Drug: NLY01; NLY01 is a pegylated exenatide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in normalized (for head size) brain parenchymal volume (nBPV)	Change in normalized (for head size) nBPV (mL). Measured from randomization to end of treatment (approximately 96 weeks). Presented as mean and standard deviation	Baseline, week 48, and week 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in normalized gray matter volume (mL)	Presented as mean and standard deviation Measured from randomization to end of treatment (approximately 96 weeks).	Baseline, week 48, and week 96
Change in thalamic volume (mL)	Measured from randomization to end of treatment (up to 96 weeks). Presented as mean and standard deviation.	Baseline, week 48, and week 96
Change in cortical thickness (mm)	Measured from randomization to end of treatment (approximately 96 weeks), Presented as mean and standard deviation.	Baseline, week 48, and week 96
Change in retinal nerve fiber layer thickness	Measured in μm, from randomization to end of treatment (approximately 96 weeks),	Baseline, week 48, and week 96
Change in ganglion cell/inner plexiform thickness	Measured in μm, from randomization to end of treatment (approximately 96 weeks),	Baseline, week 48, and week 96
Disability progression as assessed by the Expanded Disability Status Scale (EDSS)	Expanded Disability Status Scale (EDSS). Scale range 0-10; higher score is worse disability progression	Approximately every 24 weeks, up to 96 weeks
Disability progression as assessed by the Multiple Sclerosis Functional Composite (MSFC)	The Multiple Sclerosis Functional Composite (MSFC) calculates a single Z-score from tests of ambulation, arm dexterity, and cognition. Scores are converted to a z score with a mean and standard deviation. A higher Z-score indicates better function.	Approximately every 24 weeks, up to 96 weeks
Disability progression as assessed by the Expanded Disability Status Scale-Plus	The EDSS-plus allows for documentation of progression as a composite value, considering progression as having occurred if any one of the following occurs: 20% increase in timed 25-foot walk or 9-hole peg test, or a 1.0-point increase in EDSS (if baseline is 5.5 or less) or a 0.5-point increase (if baseline is >5.5).	Approximately every 24 weeks, up to 96 weeks
Patient-reported disability progression as assessed by the Patient-Determined Disease Steps	Patient-Determined Disease Steps score range 0-8; higher is worse progression	Approximately every 24 weeks, up to 96 weeks
Change in self-reported anxiety as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Anxiety Subscale	Quality of Life in Neurological Disorders (Neuro-QOL) Anxiety Subscale. Higher scores indicate more of the domain; distribution of T-Score has a mean of 50, standard deviation of 10.	Approximately every 24 weeks, up to 96 weeks
Change in self-reported depression as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Depression Subscale	Quality of Life in Neurological Disorders (Neuro-QOL) Depression Subscale. Higher scores indicate more of the domain; distribution of T-Score has a mean of 50, standard deviation of 10.	Approximately every 24 weeks, up to 96 weeks
Change in self-reported fatigue as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Fatigue Subscale	Quality of Life in Neurological Disorders (Neuro-QOL) Fatigue Subscale. Higher scores indicate more of the domain; distribution of T-Score has a mean of 50, standard deviation of 10.	Approximately every 24 weeks, up to 96 weeks
Change in self-reported upper extremity function as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Upper Extremity Function Subscale	Quality of Life in Neurological Disorders (Neuro-QOL) Upper Extremity Function Subscale. Higher scores indicate more of the domain; distribution of T-Score has a mean of 50, standard deviation of 10.	Approximately every 24 weeks, up to 96 weeks
Change in self-reported lower extremity function as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Lower Extremity Function Subscale	Quality of Life in Neurological Disorders (Neuro-QOL) Lower Extremity Function Subscale. Higher scores indicate more of the domain; distribution of T-Score has a mean of 50, standard deviation of 10.	Approximately every 24 weeks, up to 96 weeks
Change in self-reported cognitive function as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Cognitive Function Subscale	Quality of Life in Neurological Disorders (Neuro-QOL) Cognitive Function Subscale. Higher scores indicate more of the domain; distribution of T-Score has a mean of 50, standard deviation of 10.	Approximately every 24 weeks, up to 96 weeks
Change in positive affect/well-being as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Positive Affect/Well-being Subscale	Quality of Life in Neurological Disorders (Neuro-QOL) Positive Affect/Well-being Subscale. Higher scores indicate more of the domain; distribution of T-Score has a mean of 50, standard deviation of 10.	Approximately every 24 weeks, up to 96 weeks
Change in self-reported sleep disturbance as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Sleep Disturbance Subscale	Quality of Life in Neurological Disorders (Neuro-QOL) Sleep Disturbance Subscale. Higher scores indicate more of the domain; distribution of T-Score has a mean of 50, standard deviation of 10.	Approximately every 24 weeks, up to 96 weeks
Change in self-reported ability to participate in social roles Quality of Life in Neurological Disorders (Neuro-QOL) Ability to Participate in Social Roles Subscale	Quality of Life in Neurological Disorders (Neuro-QOL) Ability to Participate in Social Roles Subscale. Higher scores indicate more of the domain; distribution of T-Score has a mean of 50, standard deviation of 10.	Approximately every 24 weeks, up to 96 weeks
Change in self-reported stigma as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Stigma Subscale	Quality of Life in Neurological Disorders (Neuro-QOL) Stigma Subscale. Higher scores indicate more of the domain; distribution of T-Score has a mean of 50, standard deviation of 10.	Approximately every 24 weeks, up to 96 weeks
Adverse events	Proportion of individuals in each arm experiencing adverse events	From randomization to week 96
Serious adverse events	Proportion of individuals in each arm experiencing serious adverse events	From randomization to week 96

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Multiple Sclerosis Society; Race to Erase MS
• Investigators: Principal Investigator: Ellen M Mowry, MD, MCR, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 24, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis
• Other Study ID Numbers: IRB00454859

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) that underlie the results reported in this publication, along with the protocol and analysis plan, will be available upon reasonable request to qualified researchers. Requests must include a proposal and are contingent on meeting regulatory approvals, including a signed data use agreement.
• IPD Sharing Time Frame: Data will be available 6 months after publication and remain accessible for 12-24 months.
• IPD Sharing Access Criteria: Qualified researchers who have completed and signed approvals for data sharing.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No