Non-inferiority Study of Frexalimab Subcutaneous Administration Compared to Intravenous Administration in Adult Participants With Multiple Sclerosis

Официальное название

A Randomized, Phase 3, Open-label Study to Investigate Pharmacokinetics, Safety, and Efficacy of Subcutaneous Compared to Intravenous Frexalimab in Adult Participants With Multiple Sclerosis

Обзор

This is a randomized, open-label, parallel, Phase 3 study with 2-arms for treatment. The purpose of this study is to evaluate SC administration of frexalimab every 4 weeks (q4w) compared to IV administration of frexalimab q4w in male and female participants with RMS and nrSPMS (aged 18 to 60 years at the time of enrollment). People diagnosed with MS are eligible for enrollment as long as they meet all the inclusion criteria and none of the exclusion criteria. Study details include: The study intervention duration will be 48 weeks (12 months) for Parts A and B combined. Optional Part C will last until the initiation of a long term safety study for Frexalimab.The follow up duration after the end of study intervention (in case of discontinuation) will be 6 months. The number of scheduled visits (Parts A and B) will be 17 for participants receiving frexalimab SC or IV, with an on-site visit frequency of every month between Week 4 and Week 24 in Part A, then every 1 to 3 months in Part B, then every 6 months in Part C. Participants discontinuing treatment before the End of Study will have an additional 3 follow-up visits.

Вмешательства

• Препарат Frexalimab
  Pharmaceutical form:Solution for injection-Route of administration:SC injection
• Препарат Frexalimab
  Pharmaceutical form:Concentrate for solution for infusion-Route of administration:IV infusion
• Препарат MRI contrast-enhancing preparations
  Route of administration:IV injection

Первичные конечные точки

• Area under the curve over the interval W20 to W24(part A) [Срок оценки: Until Week 24]
• Trough concentration at steady state(part A) [Срок оценки: Until Week 24]

Вторичные конечные точки (11)

• Frexalimab plasma concentrations over time (part A for IV Arm Part A, B, C for SC arm) [Срок оценки: Until Week 24 for IV arm, Until EOS for SC arm ( until Week 96)]
• Pharmacokinetic parameters: Cmax(part A) [Срок оценки: Until Week 24]
• Pharmacokinetic parameters: Tmax(part A) [Срок оценки: Until Week 24]
• Number of participants with adverse events, SAEs, AEs leading to permanent study intervention discontinuation, AESIs, and potentially clinically significant abnormality(PCSA) in laboratory tests, and vital signs during the study period [Срок оценки: Until Week 96]
• Incidence of ADAs over time. (part A, B and C) [Срок оценки: through study completion, an average of 48 weeks]
• Total number of Gd-enhancing T1 lesions at W12 and W24(part A) [Срок оценки: At Week 12 and Week 24]
• Time to onset of confirmed disability worsening (CDW)/ confirmed disability progression(CDP) confirmed over 3 months [Срок оценки: Until week 96]
• Medical device AEs, ADEs, SAEs, SADEs and device deficiencies throughout the study [Срок оценки: Until week 96]
• Percentage of participants that prefer SC administration over IV administration assessed by Items 13 and 14 of the PESQ at Week 48 completed by participants that switched from IV to SC in Part B. [Срок оценки: From week 24 to week 48]
• Total number of GdE T1 lesions at W48(part B) [Срок оценки: At week 48]
• Total number of GdE T1 lesions at W96 and yearly thereafter.(part C) [Срок оценки: At week 96 and yearly thereafter]

Критерии участия

Критерии включения

The participant must qualify for inclusion per either Group A or B criteria as detailed below, meeting all the inclusion criteria of the applicable group:

Group A (RMS)

• The participant must be 18 to 55 years of age, inclusive, at the time of signing the informed consent.
• The participant must have been diagnosed with RMS in accordance with the 2017 revised McDonald criteria.
• The participant must have an Expanded Disability Status Scale (EDSS) score of ≤5.5 at the first visit (Screening Visit).
• The participant must have at least 1 of the following prior to screening:

• 1 documented relapse within the previous year OR
• 2 documented relapses within the previous 2 years, OR
• 1 documented Gd enhancing lesion on an MRI scan within the previous year. Group B (nrSPMS)
• Participant must have a previous diagnosis of RRMS in accordance with the 2017 revised McDonald criteria
• The participant must be 18 to 60 years of age, inclusive, at the time of signing the informed consent.
• The participant must have a current diagnosis of SPMS in accordance with the clinical course criteria revised in 2013.
• The participant must have documented evidence of disability progression observed during the 12 months before screening.
• The participant must have an absence of clinical relapses for at least 24 months.
• The participant must have an EDSS score between 3.0 and 6.5 points, inclusive, at the first visit (Screening Visit).

Participants from Group A and Group B are eligible to be included in the study only if all of the following criteria also apply:

\- Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Критерии исключения

• The participant has been diagnosed with primary progressive MS according to the 2017 revision of the McDonald diagnostic criteria.
• The participant has a history of infection or may be at risk for infection:
• Fever within 28 days of the Screening Visit
• Presence of psychiatric disturbance or substance abuse
• History, clinical evidence, suspicion or significant risk for thromboembolic events, as well as myocardial infarction, stroke, and/or antiphospholipid syndrome and any participants requiring antithrombotic treatment.
• Current hypogammaglobulinemia defined by Ig levels (IgG and/or IgM) below the LLN at screening or a history of primary hypogammaglobulinemia.
• A history or presence of disease that can mimic MS symptoms.
• The participant has a contraindication for MRI.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

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

Открытое

Основная цель

Лечение

Центры проведения

США · 22 центра

• North Central Neurology Associates- Site Number : 8401100 — Cullman
• Alabama Neurology Associates- Site Number : 8400115 — Homewood
• Center for Neurology and Spine - Phoenix - East Bell Road- Site Number : 8400195 — Phoenix
• Perseverance Research Center- Site Number : 8400138 — Scottsdale
• Private Practice - Dr. Regina Berkovich- Site Number : 8400005 — West Hollywood
• Advanced Neurology of Colorado- Site Number : 8400148 — Fort Collins
• Neurology of Central Florida- Site Number : 8400147 — Altamonte Springs
• Aqualane Clinical Research- Site Number : 8400026 — Naples
• … и ещё 14 центров

Бельгия · 5 центров

• Investigational Site Number : 0560001 — Bruges
• Investigational Site Number : 0560008 — Brussels
• Investigational Site Number : 0560006 — Ghent
• Investigational Site Number : 0560007 — Kortrijk
• Investigational Site Number : 0560005 — Overpelt

Китай · 4 центра

• Investigational Site Number : 1560005 — Пекин
• Investigational Site Number : 1560004 — Чэнду
• Investigational Site Number : 1561029 — Чэнду
• Investigational Site Number : 1560010 — Jiazhuang

Япония · 3 центра

• Investigational Site Number : 3920017 — Sapporo
• Investigational Site Number : 3920008 — Yahaba
• Investigational Site Number : 3920001 — Kyoto

Идентификаторы

NCT: NCT07325292 · EFC18098 · 2024-519304-28 · U1111-1306-7563

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗