Multiple Sclerosis
Conditions
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).
Interventions
DRUGNLY01
NLY01 is a pegylated exenatide
DRUGPlacebo
Placebo (saline solution)
Sponsors
Johns Hopkins University
National Multiple Sclerosis Society
Race to Erase MS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in normalized (for head size) brain parenchymal volume (nBPV) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in normalized gray matter volume (mL) | 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) | 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) | 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 | 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 | 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) | 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) | 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 | 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 | 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 | 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. |
| Change in self-reported depression as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Depression Subscale | Approximately every 24 weeks, up to 96 weeks | 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. |
| Change in self-reported fatigue as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Fatigue Subscale | Approximately every 24 weeks, up to 96 weeks | 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. |
| Change in self-reported upper extremity function as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Upper Extremity Function Subscale | Approximately every 24 weeks, up to 96 weeks | 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. |
| Change in self-reported lower extremity function as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Lower Extremity Function Subscale | Approximately every 24 weeks, up to 96 weeks | 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. |
| Change in self-reported cognitive function as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Cognitive Function Subscale | Approximately every 24 weeks, up to 96 weeks | 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. |
| Change in positive affect/well-being as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Positive Affect/Well-being Subscale | Approximately every 24 weeks, up to 96 weeks | 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. |
| Change in self-reported sleep disturbance as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Sleep Disturbance Subscale | Approximately every 24 weeks, up to 96 weeks | 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. |
| 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 | Approximately every 24 weeks, up to 96 weeks | 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. |
| Change in self-reported stigma as assessed by the Quality of Life in Neurological Disorders (Neuro-QOL) Stigma Subscale | Approximately every 24 weeks, up to 96 weeks | 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. |
| Adverse events | From randomization to week 96 | Proportion of individuals in each arm experiencing adverse events |
| Serious adverse events | From randomization to week 96 | Proportion of individuals in each arm experiencing serious adverse events |
Countries
United States
Contacts
CONTACTStudy Manager
PRINCIPAL_INVESTIGATOREllen M Mowry, MD, MCR
Johns Hopkins University
Outcome results
None listed