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

Официальное название

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

Обзор

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).

Вмешательства

• Препарат NLY01
  NLY01 is a pegylated exenatide
• Препарат Placebo
  Placebo (saline solution)

Первичные конечные точки

• Change in normalized (for head size) brain parenchymal volume (nBPV) [Срок оценки: Baseline, week 48, and week 96]

Вторичные конечные точки (12)

• Change in normalized gray matter volume (mL) [Срок оценки: Baseline, week 48, and week 96]
• Change in thalamic volume (mL) [Срок оценки: Baseline, week 48, and week 96]
• Change in cortical thickness (mm) [Срок оценки: Baseline, week 48, and week 96]
• Change in retinal nerve fiber layer thickness [Срок оценки: Baseline, week 48, and week 96]
• Change in ganglion cell/inner plexiform thickness [Срок оценки: Baseline, week 48, and week 96]
• Disability progression as assessed by the Expanded Disability Status Scale (EDSS) [Срок оценки: Approximately every 24 weeks, up to 96 weeks]
• Disability progression as assessed by the Multiple Sclerosis Functional Composite (MSFC) [Срок оценки: Approximately every 24 weeks, up to 96 weeks]
• Disability progression as assessed by the Expanded Disability Status Scale-Plus [Срок оценки: Approximately every 24 weeks, up to 96 weeks]
• Patient-reported disability progression as assessed by the Patient-Determined Disease Steps [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Approximately every 24 weeks, up to 96 weeks]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Johns Hopkins University — Baltimore
• Mount Sinai School of Medicine — New York

Идентификаторы

NCT: NCT07497399 · IRB00454859

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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