Multiple SclerosisPhase 2TAG-MSNCT07497399
Targeting Agonists of Glucagon-like Peptide-1 Receptor for Multiple Sclerosis
A Phase 2 study testing NLY01 in people with Multiple Sclerosis, run by Johns Hopkins University at 3 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- NLY01
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 3 sitesUnited States
- Study dates
- 28 Apr 2026to Jan 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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)***
Show all 16Show fewer
- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Recruiting
Johns Hopkins University
Baltimore, Maryland, 21287
Margaret Vieira, 667-306-8153, mvieira4@jh.edu
Ellen Mowry, MD, MCR
- Not yet recruiting
University of Kansas Medical Center
Kansas City, Kansas, 66103
Sara Baker, 913-588-6937, sbaker12@kumc.edu
Sharon Lynch, MD
- Recruiting
Mount Sinai School of Medicine
New York, New York, 10029
Susan Filomena, 212-241-4364, susan.e.filomena@mssm.edu
About this study
Official title: 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).
- Conditions
- Multiple Sclerosis
- Being tested
- NLY01, Placebo
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NLY01Drug
NLY01 is a pegylated exenatide
PlaceboDrug
Placebo (saline solution)
| Study group | Role | What they receive |
|---|---|---|
| NLY01 (Study Drug) | Active comparator | 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. Receives: Drug: NLY01 |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline, week 48, and week 96
Secondary outcomes (21)
Change in normalized gray matter volume (mL)
Presented as mean and standard deviation Measured from randomization to end of treatment (approximately 96 weeks).
Measured: 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.
Measured: 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.
Measured: 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),
Measured: 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),
Measured: 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
Measured: 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.
Measured: 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).
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Approximately every 24 weeks, up to 96 weeks
Adverse events
Proportion of individuals in each arm experiencing adverse events
Measured: From randomization to week 96
Serious adverse events
Proportion of individuals in each arm experiencing serious adverse events
Measured: From randomization to week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2026
- Study start28 Apr 2026
- Primary completionJan 2030 (estimated)
- Study completionJan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Multiple Sclerosis Society, Race to Erase MS
- Responsible party
- Sponsor
- Investigators
- Ellen M Mowry, MD, MCR, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07497399
- Sponsor's protocol ID
- IRB00454859
- Acronym
- TAG-MS
- Status last verified
- Nov 2026
- First submitted
- 11 Mar 2026
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Agonists of Glucagon-like Peptide-1 Receptor for Multiple Sclerosis (TAG-MS): A Phase 2, Randomized, Double-Blind, Parallel-Arm Study
- ClinicalTrials.gov ID
- NCT07497399
- Acronym / sponsor ID
- TAG-MS / IRB00454859
- Conditions
- Multiple Sclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Multiple Sclerosis Society, Race to Erase MS
- Study start
- 28 Apr 2026 (actual)
- Primary completion
- Jan 2030 (estimated)
- Study completion
- Jan 2030 (estimated)
- First posted
- 27 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NLY01 (Study Drug) | Active comparator | Drug: NLY015 mg subcutaneous weekly for the first 4 weeks, then 10 mg subcutaneous weekly, with pre-planned dose adjustments if adverse events prevent full dosage. |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NLY01NLY01 is a pegylated exenatide | Drug | NLY01 (Study Drug) |
| PlaceboPlacebo (saline solution) | Drug | Placebo |
Primary outcome
Change in normalized (for head size) brain parenchymal volume (nBPV)
Time frame: Baseline, week 48, and week 96
Change in normalized (for head size) nBPV (mL). Measured from randomization to end of treatment (approximately 96 weeks). Presented as mean and standard deviation
21 secondary outcomes
Change in normalized gray matter volume (mL)
Time frame: Baseline, week 48, and week 96
Change in thalamic volume (mL)
Time frame: Baseline, week 48, and week 96
Change in cortical thickness (mm)
Time frame: Baseline, week 48, and week 96
Change in retinal nerve fiber layer thickness
Time frame: Baseline, week 48, and week 96
Change in ganglion cell/inner plexiform thickness
Time frame: Baseline, week 48, and week 96
Disability progression as assessed by the Expanded Disability Status Scale (EDSS)
Time frame: Approximately every 24 weeks, up to 96 weeks
Disability progression as assessed by the Multiple Sclerosis Functional Composite (MSFC)
Time frame: Approximately every 24 weeks, up to 96 weeks
Disability progression as assessed by the Expanded Disability Status Scale-Plus
Time frame: Approximately every 24 weeks, up to 96 weeks
Patient-reported disability progression as assessed by the Patient-Determined Disease Steps
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Approximately every 24 weeks, up to 96 weeks
Adverse events
Time frame: From randomization to week 96
Serious adverse events
Time frame: From randomization to week 96
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Individual participant dataSharing planned: Yes. 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.
Related trials for Multiple Sclerosis
RecruitingPhase 2
Metformin as an add-on or Monotherapy in Treatment of Aging People With Multiple Sclerosis (MS)
Multiple Sclerosis
RecruitingObservational study
Pain Phenotypes in Individuals With Multiple Sclerosis
Multiple Sclerosis, Chronic Pain
Not yet recruiting
Evaluating the Effect of the Zeen Mobility Device on Clinical Practicality, Safety, and Impact (Via Assessments of Walking, Standing Tolerance, Balance, Endurance, Effort, and Participation in Daily Tasks) in an Outpatient Rehabilitation Setting for Individuals With Mobility Impairments.
Stroke, Parkinson's Disease (PD)
RecruitingPhase 3
Dalfampridine Combined With Physical Therapy for Mobility Impairment in Multiple Sclerosis
Multiple Sclerosis
RecruitingObservational study
Study of the Disease Process of Lymphangioleiomyomatosis
Lung Disease, Pneumothorax
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ellen M Mowry, MD, MCR principal investigator
Johns Hopkins University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NLY01 in people with Multiple Sclerosis, run by Johns Hopkins University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Study Manager (667-306-8153, mvieira4@jh.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in normalized (for head size) brain parenchymal volume (nBPV) (time frame: Baseline, week 48, and week 96). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.