TAG-MS

RecruitingPhase 2

Targeting Agonists of Glucagon-like Peptide-1 Receptor for Multiple Sclerosis

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

Lead sponsor

Johns Hopkins University

Asset

Exenatide

GLP-1 agonist

Listed sites

Recruiting sites

Enrollment

120

estimated

Study population

Multiple sclerosis, Obesity / overweight

Key I/E criterion

•BMI ≥27

Primary endpoint

•Normalized (for head size) brain parenchymal volume (nBPV)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT07497399

Org study IDIRB00454859

Timeline

Milestones

Study first posted2026-03-27actual

Study start2026-04-28actual

Last update posted2026-05-05actual

Primary completion2030-01estimated (month precision)

Study completion2030-01estimated (month precision)

Assets

Investigational agents

Exenatide

Study populations

Who this study enrolls

Multiple sclerosisObesity / overweight

Eligibility

Who can enroll

Minimum age18 Years

Maximum age60 Years

SexAll

Healthy volunteersNot accepted

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.

Endpoints (22)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Patient-reported / QoL

Other clinical outcomes

Safety / tolerability / PK

Patient-reported / QoL

11 endpoints

Secondary/protocol endpoint

Patient-reported disability progression as assessed by the Patient-Determined Disease Steps

Time frame:Approximately every 24 weeks, up to 96 weeks

change from baseline, improvement

Secondary/protocol endpoint

Change in self-reported anxiety as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Anxiety Subscale

Time frame:Approximately every 24 weeks, up to 96 weeks

change from baseline, improvement

Secondary/protocol endpoint

Change in self-reported depression as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Depression Subscale

Time frame:Approximately every 24 weeks, up to 96 weeks

change from baseline, improvement

Secondary/protocol endpoint

Change in self-reported fatigue as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Fatigue Subscale

Time frame:Approximately every 24 weeks, up to 96 weeks

change from baseline, improvement

Secondary/protocol endpoint

Change in self-reported upper extremity function as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Upper Extremity Function Subscale

Time frame:Approximately every 24 weeks, up to 96 weeks

change from baseline, improvement

Secondary/protocol endpoint

Change in self-reported lower extremity function as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Lower Extremity Function Subscale

Time frame:Approximately every 24 weeks, up to 96 weeks

change from baseline, improvement

Secondary/protocol endpoint

Change in self-reported cognitive function as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Cognitive Function Subscale

Time frame:Approximately every 24 weeks, up to 96 weeks

change from baseline, improvement

Secondary/protocol endpoint

Change in positive affect/well-being as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Positive Affect/Well-being Subscale

Time frame:Approximately every 24 weeks, up to 96 weeks

change from baseline, improvement

Secondary/protocol endpoint

Change in self-reported sleep disturbance as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Sleep Disturbance Subscale

Time frame:Approximately every 24 weeks, up to 96 weeks

change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:Approximately every 24 weeks, up to 96 weeks

change from baseline, improvement

Secondary/protocol endpoint

Change in self-reported stigma as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Stigma Subscale

Time frame:Approximately every 24 weeks, up to 96 weeks

change from baseline, improvement

Safety / tolerability / PK

2 endpoints

Secondary/protocol endpoint

Adverse events

Time frame:From randomization to week 96

Treatment-emergent AEs (any)

threshold achievement, event

Secondary/protocol endpoint

Serious adverse events

Time frame:From randomization to week 96

Serious AEs (any)

threshold achievement, event

Other clinical outcomes

9 endpoints

Primary/protocol endpoint/low confidence

Change in normalized (for head size) brain parenchymal volume (nBPV)

Time frame:Baseline, week 48, and week 96

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change in normalized gray matter volume (mL)

Time frame:Baseline, week 48, and week 96

change from baseline, improvement

Secondary/protocol endpoint

Change in thalamic volume (mL)

Time frame:Baseline, week 48, and week 96

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change in cortical thickness (mm)

Time frame:Baseline, week 48, and week 96

change from baseline, descriptive

Secondary/protocol endpoint

Change in retinal nerve fiber layer thickness

Time frame:Baseline, week 48, and week 96

change from baseline, improvement

Secondary/protocol endpoint

Change in ganglion cell/inner plexiform thickness

Time frame:Baseline, week 48, and week 96

change from baseline, improvement

Secondary/protocol endpoint

Disability progression as assessed by the Expanded Disability Status Scale (EDSS)

Time frame:Approximately every 24 weeks, up to 96 weeks

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Disability progression as assessed by the Multiple Sclerosis Functional Composite (MSFC)

Time frame:Approximately every 24 weeks, up to 96 weeks

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Disability progression as assessed by the Expanded Disability Status Scale-Plus

Time frame:Approximately every 24 weeks, up to 96 weeks

composite event, event

componentstimed 25 foot walk 20pct worsening, nine hole peg test 20pct worsening, edss increase threshold

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.