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A Study to Evaluate, Safety, Tolerability, and PK of AP-101 in Participants With ALS

28 сентября 2026 г. обновлено: AL-S Pharma

A Phase 2a, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of AP-101 in Participants With Sporadic or SOD1-Associated ALS

The purpose of this study is to evaluate the safety, tolerability, PK, and PD of AP-101 in participants with fALS and sALS.

Обзор исследования

Статус

Завершенный

Условия

Вмешательство/лечение

Подробное описание

This Phase 2a, multicenter, randomized, double-blind, placebo-controlled study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamic markers of AP-101 in adults with sporadic ALS or SOD1-associated ALS. A total of 73 participants were randomized within each ALS cohort in a 2:1 ratio to receive AP-101 or placebo during a 24-week double-blind treatment period.

Participants assigned to AP-101 received a 500 mg intravenous loading dose on Day 1, a 2500 mg intravenous dose on Day 2, and 2500 mg intravenously every 3 weeks beginning on Day 22 through Week 24. Participants assigned to placebo received matching intravenous infusions on the same schedule. Stable use of locally approved ALS treatments was permitted.

Participants who completed the double-blind period could enter an optional 24-week open-label extension in which all participants received AP-101. To maintain the integrity of the double-blind period, the initial dose in the open-label extension remained blinded. Participants were followed for safety and pharmacokinetic assessments for up to 16 weeks after their final study dose.

The primary assessments evaluated adverse events, serious adverse events, immunogenicity, vital signs, clinical laboratory assessments, physical and neurological examinations, electrocardiograms, and changes in weight. Secondary assessments included serum pharmacokinetics, AP-101 concentrations in cerebrospinal fluid, and the neurofilament biomarkers phosphorylated neurofilament heavy chain (pNfH) and neurofilament light chain (NfL). Exploratory assessments included the ALS Functional Rating Scale-Revised, slow vital capacity, muscle strength, King's staging, survival and ventilation outcomes, quality of life, and cerebrospinal fluid total and misfolded SOD1.

Тип исследования

Интервенционный

Регистрация (Действительный)

73

Фаза

  • Фаза 2

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Места учебы

  • Бельгия
      • Leuven, Бельгия, 3000
        • Department of Neurology, University Hospitals
  • Германия
      • Berlin, Германия, 13353
        • Charité
      • Bonn, Германия, 53127
        • Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)
      • Hanover, Германия, 30625
        • Hannover Medical School
      • Ulm, Германия, 89081
        • Ulm University Hospital
  • Канада
    • Alberta
      • Edmonton, Alberta, Канада, AB T6G 1Z1
        • ALS clinic at the Kaye Edmonton Clinic, University of Alberta
    • Ontario
      • London, Ontario, Канада, ON N6A 5W9
        • London Health Sciences Centre - Victoria Hospital
      • Toronto, Ontario, Канада, M4N 3M5
        • ALS Research Sunnybrook Health Sciences Centre
    • Quebec
      • Montreal, Quebec, Канада, H3A 2B4
        • Montreal Neurological Institute and Hospital / Dr Genge
  • Соединенные Штаты
    • California
      • La Jolla, California, Соединенные Штаты, 92037
        • UC San Diego, ACTRI
  • Швеция
      • Stockholm, Швеция, 113 61
        • Studieenheten Akademiskt specialistcentrum, SLSO
      • Umeå, Швеция, SE- 901 85
        • Norrlands universitetssjukhus/ University Hospital of Northern Sweden (NUS)
  • Южная Корея
      • Seoul, Южная Корея, 04763
        • Hanyang University Medical Center

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

18 лет и старше (Взрослый, Пожилой взрослый)

Принимает здоровых добровольцев

Нет

Полы, имеющие право на обучение

Все

Описание

Inclusion Criteria:

  • All participants must adhere to contraception restrictions
  • Female participants of childbearing potential must adhere to contraception restrictions
  • Have possible, clinically probable, clinically probable-laboratory supported or definite familial or sporadic ALS in accordance with the El-Escorial criteria or who have a diagnosis of ALS as defined by the Gold Coast Criteria; progressive motor impairment documented by history or repeated clinical examination, preceded by normal motor development, and presence of upper and lower motor neuron dysfunction in at least 1 body region or lower motor neuron dysfunction in at least 2 body regions and investigations excluding other conditions
  • In familial ALS participants, a confirmed pathogenic superoxide dismutase 1 (SOD1) mutation
  • Onset of symptoms (i.e, weakness) within past 24 months prior to screening, at the time of obtaining informed consent
  • Have slow vital capacity (SVC) of greater than or equal to (> or =) 50 percentage (%) of predicted values. Participants with SVC of <50% of predicted values may be permitted to enter the open-label extension, based on the opinion of the investigator
  • Absence of bilevel positive airway pressure (BiPAP)/proportional assist ventilation (PAV) > 4 hours for symptoms attributable to ALS. Use of a CPAP for pre-existing conditions will be allowed
  • If on riluzole, must be on a stable dose.
  • If on edaravone, must have completed 2 cycles and are expected to remain on the same dose throughout the study
  • Able to provide informed consent which includes compliance with the requirements and restrictions
  • Have venous access sufficient to allow for blood sampling
  • Have clinical laboratory test results within the normal reference range for the population or study site, or results with acceptable deviations that are judged to be not clinically significant by the investigator

Exclusion Criteria:

  • Have participated or currently participating in another clinical trial within 5 half-lives of baseline (Day 1)
  • Have undergone a tracheostomy for ALS symptoms
  • Are on nasal intermittent positive pressure ventilation (NIPPV) >4 hours per day for the treatment of ALS related symptoms
  • Have other causes of neuromuscular weakness
  • Have cognitive impairment, severe disease in the cardiovascular, hematological, renal system, neurodegenerative disease, pulmonary disorder, or psychiatric illness
  • Pregnant or nursing women
  • Have been exposed to any antisense treatment targeting SOD1 within 6 months of the baseline visit
  • Have undergone stem cell therapy

Учебный план

В этом разделе представлена ​​подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

  • Основная цель: Уход
  • Распределение: Рандомизированный
  • Интервенционная модель: Параллельное назначение
  • Маскировка: Двойной

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Экспериментальный: AP-101

AP-101 is administered by intravenous infusion (IV).
Лекарство: AP-101

Participants receive AP-101 by intravenous infusion (IV).
Плацебо Компаратор: Placebo

Placebo is administered by intravenous infusion (IV).
Лекарство: Placebo

Participants receive placebo by intravenous infusion (IV).

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Participants With Treatment-Emergent Adverse Events (TEAE) and Treatment-Emergent Serious Adverse Events (TESAE) During the Double-Blind Period
Временное ограничение: From the first dose through the 21-day follow-up after Week 24, approximately 27 weeks

Treatment-emergent adverse events were adverse events that began or worsened after the first dose of randomized study treatment during the double-blind period. Treatment-emergent serious adverse events met the protocol-defined criteria for seriousness. Participants experiencing more than one event within a category were counted once in that category. Results are presented separately for the sporadic ALS and SOD1-associated ALS cohorts.
From the first dose through the 21-day follow-up after Week 24, approximately 27 weeks
Number of Participants With Abnormalities in Vital Signs, Clinical Laboratory Assessments, Physical and Neurological Examinations, and Electrocardiograms
Временное ограничение: From the first dose through the 21-day follow-up after Week 24, approximately 27 weeks

Number of participants with at least one abnormality in vital signs, clinical laboratory assessments, physical examinations, neurological examinations, or electrocardiograms during the double-blind period. Participants could be included in more than one category; therefore, categories were not mutually exclusive. Results are presented separately for the sporadic ALS and SOD1-associated ALS cohorts.
From the first dose through the 21-day follow-up after Week 24, approximately 27 weeks
Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs) During the Double-Blind Period
Временное ограничение: From baseline through the 21-day follow-up after Week 24, approximately 27 weeks

Serum samples were assessed for anti-drug antibodies to AP-101. Participants were evaluable for treatment-emergent anti-drug antibodies if they had at least one non-missing baseline result and at least one non-missing post-baseline result. One participant was anti-drug-antibody positive at baseline and subsequently tested negative; baseline positivity was not classified as treatment-emergent. Results are presented separately for the sporadic ALS and SOD1-associated ALS cohorts. ADA testing was not assessed in placebo participants.
From baseline through the 21-day follow-up after Week 24, approximately 27 weeks

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Model-Derived Elimination Half-Life of AP-101 in Serum
Временное ограничение: From the first AP-101 dose through 16 weeks after the final AP-101 dose, up to approximately 64 weeks

The individual elimination half-life of AP-101 was estimated using empirical Bayes estimates from the final two-compartment population pharmacokinetic model. The model used pooled serum AP-101 concentration data from studies AP101-01 and AP101-02. This outcome summarizes participants from AP101-02 who were included in the final population pharmacokinetic model.
From the first AP-101 dose through 16 weeks after the final AP-101 dose, up to approximately 64 weeks
Model-Derived Area Under the Serum AP-101 Concentration-Time Curve
Временное ограничение: AUC following the second active dose: Day 2 through Day 22; AUC at steady state: the 21-day dosing interval following the participant's final active AP-101 dose, which occurred up to approximately Week 48 of the study

Individual AP-101 exposure was estimated using empirical Bayes estimates from the final two-compartment population pharmacokinetic model. Area under the concentration-time curve during the dosing interval was estimated following the second active AP-101 dose and at steady state. This outcome summarizes AP101-02 participants included in the final population pharmacokinetic model.
AUC following the second active dose: Day 2 through Day 22; AUC at steady state: the 21-day dosing interval following the participant's final active AP-101 dose, which occurred up to approximately Week 48 of the study
Model-Derived Maximum Serum AP-101 Concentration
Временное ограничение: Cmax following the second active dose: Day 2 through Day 22; Cmax at steady state: during the 21-day dosing interval following the participant's final active AP-101 dose, which occurred up to approximately Week 48 of the study.

Individual maximum serum AP-101 concentrations were estimated using empirical Bayes estimates from the final two-compartment population pharmacokinetic model. Maximum concentration was estimated following the second active AP-101 dose and at steady state. This outcome summarizes AP101-02 participants included in the final population pharmacokinetic model.
Cmax following the second active dose: Day 2 through Day 22; Cmax at steady state: during the 21-day dosing interval following the participant's final active AP-101 dose, which occurred up to approximately Week 48 of the study.
AP-101 Concentration in Cerebrospinal Fluid During the Double-Blind Period
Временное ограничение: Week 12 and Week 24 of the double-blind period

AP-101 concentrations were measured in cerebrospinal fluid to assess central nervous system exposure after repeated intravenous dosing. Samples were collected at Week 12 and Week 24 of the double-blind period and summarized by ALS cohort and visit among participants with quantifiable CSF AP-101 concentrations. Actual concentrations were reported rather than change from baseline because nearly all baseline concentrations were below the limit of quantitation.
Week 12 and Week 24 of the double-blind period
Change From Baseline in Cerebrospinal Fluid Phosphorylated Neurofilament Heavy Chain (pNfH) During the Double-Blind Period
Временное ограничение: Baseline to Week 24 of the double-blind period

Phosphorylated neurofilament heavy chain (pNfH) concentrations were measured in cerebrospinal fluid at baseline, Week 12, and Week 24. Results represent the mean change from baseline and are presented separately for the sporadic ALS and SOD1-ALS cohorts. Negative values indicate a decrease from baseline.
Baseline to Week 24 of the double-blind period
Change From Baseline in Serum Neurofilament Light Chain During the Double-Blind Period and 21-Day Follow-up
Временное ограничение: Baseline through the 21-day follow-up after Week 24, approximately 27 weeks

Neurofilament light chain (NfL) concentrations were measured in serum at baseline, Week 12, Week 24, and the 21-day follow-up after completion of double-blind treatment. Results represent the mean change from baseline and are presented separately for the sporadic ALS and SOD1-ALS cohorts. Negative values indicate a decrease from baseline.
Baseline through the 21-day follow-up after Week 24, approximately 27 weeks

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

AL-S Pharma

Следователи

  • Директор по исследованиям: Study Director, AL-S Pharma AG

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования (Действительный)

2 сентября 2021 г.

Первичное завершение (Действительный)

13 августа 2025 г.

Завершение исследования (Действительный)

13 августа 2025 г.

Даты регистрации исследования

Первый отправленный

1 сентября 2021 г.

Впервые представлено, что соответствует критериям контроля качества

1 сентября 2021 г.

Первый опубликованный (Действительный)

9 сентября 2021 г.

Обновления учебных записей

Последнее опубликованное обновление (Действительный)

30 сентября 2026 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

28 сентября 2026 г.

Последняя проверка

1 сентября 2026 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • AP101-02
  • 2020-005971-11 (Номер EudraCT)

Информация о лекарствах и устройствах, исследовательские документы

Изучает лекарственный продукт, регулируемый FDA США.

Да

Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.

Нет

Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .

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