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

NCT07497399 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IRB00454859
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (21)

• Change in normalized gray matter volume (mL)

  Baseline, week 48, and week 96

• Change in thalamic volume (mL)

  Baseline, week 48, and week 96

• Change in cortical thickness (mm)

  Baseline, week 48, and week 96

• Change in retinal nerve fiber layer thickness

  Baseline, week 48, and week 96

• Change in ganglion cell/inner plexiform thickness

  Baseline, week 48, and week 96

Study Arms (2)

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.

Drug: NLY01

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

NLY01 DRUG

NLY01 is a pegylated exenatide

NLY01 (Study Drug)

Placebo DRUG

Placebo (saline solution)

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Race to Erase MS: collaborator
• Johns Hopkins University: lead
• National Multiple Sclerosis Society: collaborator

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Ellen M Mowry, MD, MCR

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Manager

CONTACT

667-306-8153; mvieira4@jh.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2026
• First Posted: March 27, 2026
• Study Start: April 28, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be available 6 months after publication and remain accessible for 12-24 months.
• Access Criteria: Qualified researchers who have completed and signed approvals for data sharing.

Locations

US (1)