DRUG
NLY01
NLY01 is a pegylated exenatide
Status
Recruiting
Phase
Phase 2
Enrollment
120
Locations
2
Results
Not posted
Publications
0
Study 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. 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).
Interventions
DRUG
NLY01 is a pegylated exenatide
DRUG
Placebo (saline solution)
Timeline
First posted
Mar 27, 2026
Study start
Apr 28, 2026
Primary completion
Jan 2030
Study completion
Jan 2030
Results posted
Not reported
Registry updated
Jul 17, 2026
Outcomes
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
Change in normalized gray matter volume (mL)
Time frame · Baseline, week 48, and week 96
Presented as mean and standard deviation Measured from randomization to end of treatment (approximately 96 weeks).
Change in thalamic volume (mL)
Time frame · Baseline, week 48, and week 96
Measured from randomization to end of treatment (up to 96 weeks). Presented as mean and standard deviation.
Change in cortical thickness (mm)
Time frame · Baseline, week 48, and week 96
Measured from randomization to end of treatment (approximately 96 weeks), Presented as mean and standard deviation.
Change in retinal nerve fiber layer thickness
Time frame · Baseline, week 48, and week 96
Measured in μm, from randomization to end of treatment (approximately 96 weeks),
Change in ganglion cell/inner plexiform thickness
Time frame · Baseline, week 48, and week 96
Measured in μm, from randomization to end of treatment (approximately 96 weeks),
Disability progression as assessed by the Expanded Disability Status Scale (EDSS)
Time frame · Approximately every 24 weeks, up to 96 weeks
Expanded Disability Status Scale (EDSS). Scale range 0-10; higher score is worse disability progression
Disability progression as assessed by the Multiple Sclerosis Functional Composite (MSFC)
Time frame · Approximately every 24 weeks, up to 96 weeks
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.
Disability progression as assessed by the Expanded Disability Status Scale-Plus
Time frame · Approximately every 24 weeks, up to 96 weeks
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).
Patient-reported disability progression as assessed by the Patient-Determined Disease Steps
Time frame · Approximately every 24 weeks, up to 96 weeks
Patient-Determined Disease Steps score range 0-8; higher is worse progression
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
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.
Eligibility
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 locations
United States. Showing up to 24 locations stored in the fast local snapshot.
Johns Hopkins University
Baltimore, Maryland, United States
Mount Sinai School of Medicine
New York, New York, United States
Publications
No PMID-linked publications were present in this registry snapshot.
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