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Um estudo avaliando a eficácia, segurança, farmacocinética e farmacodinâmica do crovalimabe em participantes pediátricos com síndrome hemolítico-urêmica atípica (SHUa) (COMMUTE-p)

17 de agosto de 2026 atualizado por: Hoffmann-La Roche

Um estudo de fase III, multicêntrico, de braço único avaliando a eficácia, segurança, farmacocinética e farmacodinâmica do crovalimabe em pacientes pediátricos com síndrome hemolítico-urêmica atípica (SHUa)

Este estudo tem como objetivo avaliar a eficácia e segurança do crovalimabe em participantes pediátricos com SHUa.

Visão geral do estudo

Status

Ativo, não recrutando

Condições

Intervenção / Tratamento

Tipo de estudo

Intervencional

Inscrição (Real)

41

Estágio

  • Fase 3

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

  • Brasil
    • São Paulo
      • São Paulo, São Paulo, Brasil, 05403-900
        • Inst. Da Criança- Faculdade de Medicina Usp
  • Bélgica
      • Ghent, Bélgica, 9000
        • UZ Gent
      • Leuven, Bélgica, 3000
        • UZ Leuven Gasthuisberg
  • Canadá
    • Quebec
      • Montreal, Quebec, Canadá, H3T 1C5
        • CHU Sainte-Justine
  • China
      • Beijing, China, 100034
        • Peking University First Hospital
      • Beijing, China, 100045
        • Beijing Children's Hospital, Capital Medical University
      • Hangzhou, China, 310051
        • The children's hospital , Zhejiang university school of medicine
  • Estados Unidos
    • Colorado
      • Aurora, Colorado, Estados Unidos, 80045
        • Children's Hospital Colorado
    • Nebraska
      • Omaha, Nebraska, Estados Unidos, 68198
        • University of Nebraska
    • New Jersey
      • Hackensack, New Jersey, Estados Unidos, 07601
        • Hackensack University Medical Center
  • França
      • Montpellier, França, 34295
        • Hopital Arnaud de Villeneuve
      • Paris, França, 75743
        • Gh Necker Enfants Malades
  • Japão
      • Aichi, Japão, 474-8710
        • Aichi Children?s Health and Medical Center
      • Chibashi, Chibaken, Japão, 266-0007
        • Chiba Children's Hospital
  • México
      • Zapopan, México, 45116
        • Hospital de Especialidades Puerta de Hierro S.A de C.V.
  • Polônia
      • Gdansk, Polônia, 80-294
        • Uniwersyteckie Centrum Kliniczne
      • Lodz, Polônia, 93-338
        • Instytut ?Centrum Zdrowia Matki Polki
  • Índia
    • Gujarat
      • Ahmedabad, Gujarat, Índia, 380016
        • Institute of Kidney Diseases and Research Centre
    • Haryana
      • Gurgaon, Haryana, Índia, 122001
        • Medanta-The Medicity
    • National Capital Territory of Delhi
      • New Delhi, National Capital Territory of Delhi, Índia, 110029
        • All India Institute of Medical Sciences (AIIMS)

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

4 semanas a 17 anos (Filho)

Aceita Voluntários Saudáveis

Não

Descrição

Critério de inclusão:

  • Peso corporal >= 5 kg na triagem.
  • Vacinação contra Neisseria meningitis sorotipos A, C, W e Y; vacinação contra o sorotipo B, de acordo com as recomendações nacionais de vacinação.
  • Vacinação contra Haemophilus influenzae tipo B e Streptococcus pneumoniae, de acordo com as recomendações nacionais de vacinação.
  • Para pacientes que continuam recebendo outras terapias concomitantemente com crovalimabe (por exemplo, imunossupressores, corticosteroides, mTORi ou inibidores de calcineurina): dose estável por >=28 dias antes da triagem e até a primeira administração de crovalimabe.
  • Para participantes do sexo feminino com potencial para engravidar: um acordo para permanecer abstinente ou usar contracepção.
  • Os participantes com transplante renal anterior são elegíveis se tiverem um histórico conhecido de SHUa mediada por complemento antes do transplante renal.
  • Início da apresentação inicial de TMA dentro de 28 dias antes da primeira dose de crovalimabe (somente para Coorte Naive).
  • Tratamento documentado com eculizumab ou ravulizumab (apenas para Switch Cohort).
  • Evidência clínica de resposta a um inibidor de C5 (somente para Switch Cohort).
  • TMA mal controlado após tratamento com outro inibidor de C5 (somente para participantes de C5 SNP na coorte pré-tratada).
  • Polimorfismo C5 conhecido (apenas para participantes C5 SNP na coorte pré-tratada).

Critério de exclusão:

  • MAT associada a doença renal não relacionada à SHUa.
  • Teste de Coombs direto positivo.
  • Diálise crônica e/ou doença renal terminal.
  • Identificado TMA relacionado à exposição a drogas.
  • Presença ou história de uma condição que possa desencadear MAT, como malignidade, transplante de medula óssea ou órgão (exceto transplante de rim) ou doença autoimune.
  • História de doença renal, exceto SHUa.
  • Histórico de infecção por Neisseria meningitidis dentro de 6 meses após a inscrição no estudo.
  • Deficiência imunológica conhecida ou suspeita (por exemplo, história de infecções recorrentes frequentes).
  • Teste de HIV positivo.
  • Infecção bacteriana, viral ou fúngica sistêmica ativa dentro de 14 dias antes da primeira administração de crovalimabe.
  • Presença de febre (>= 38oC) até 7 dias antes da primeira administração de crovalimabe.
  • Disfunção ou falha de órgãos multissistêmicos.
  • Tratamento recente com IVIg.
  • Grávida ou amamentando ou com intenção de engravidar.
  • Participação em outro estudo de tratamento intervencionista com um agente experimental ou uso de qualquer terapia experimental dentro de 28 dias após a triagem ou dentro de cinco meias-vidas desse produto experimental, o que for maior.
  • Uso recente de ácido tranexâmico.
  • Tratamento atual ou anterior com um inibidor do complemento (somente para Coorte Naive).
  • O primeiro início de troca de plasma/infusões de plasma (PE/PI) não deve ser superior a 28 dias antes da primeira administração de crovalimabe (somente para Coorte Naive).
  • PE/PI não deve ser administrado dentro de 6 horas após a primeira administração de crovalimabe (somente para Coorte Naive).
  • Receber PE/PI dentro de 8 semanas após a primeira administração de crovalimabe (apenas Switch Coorte).
  • Positivo para infecções ativas por Hepatite B e/ou C (HBV/HCV) (para participantes da coorte de troca e da coorte pré-tratada com SNP de troca de C5 que recentemente receberam tratamento com inibidor de C5).
  • Crioglobulinemia na triagem (para participantes do Switch Cohort e C5 SNP Cohort que recentemente receberam tratamento com inibidor de C5).
  • Condição documentada levando a SHUa TMA: púrpura trombocitopênica trombótica (TTP), Escherichia Coli produtora de toxina Shiga (STEC)-TMA, SHU pneumocócica, TMA secundária a defeito de cobalamina C e TMA relacionada à nefropatia por diacilglicerol quinase ε (DGKE).

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: N / D
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Crovalimabe
Os participantes serão inscritos em três coortes: [1] Coorte Naive - participantes que não foram previamente tratados com terapia com inibidores do complemento; [2] Coorte de troca - participantes que mudam para crovalimabe de outro inibidor de C5 e [3] Coorte pré-tratada (inclui participantes C5 SNP (polimorfismo de nucleotídeo único)) - participantes que receberam tratamento com outro inibidor de C5 e posteriormente o descontinuaram.
Medicamento: Crovalimabe
O crovalimab será administrado na dose de 1000 mg por via intravenosa (IV) (para participantes com peso => ​​40 a =100 kg) na Semana 1, Dia 1. Na Semana 1, Dia 2 e nas Semanas 2, 3 e 4, o crovalimabe será administrado na dose de 340 mg por via subcutânea (SC). Na semana 5 e no quarto trimestre seguinte, será administrado na dose de 680 mg SC (para participantes com peso => ​​40 a =100 kg). Inscrições de participantes com peso =20 kg a =5 kg a

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Naïve Cohort: Percentage of Participants With Complete Thrombotic Microangiopathy Response (cTMAr) Anytime From Baseline to Week 25 (After 24 Weeks on Treatment)
Prazo: From baseline up to Week 25
cTMAr was defined by meeting all of the following criteria at two separate assessments, obtained at least 4 weeks (a minimum of 26 days) apart, and any measurement in between: Platelet count ≥ lower limit of normal (LLN); Lactate dehydrogenase (LDH) ≤ upper limit of normal (ULN); and ≥ 25% decrease in serum creatinine from baseline. Participants with normalized creatinine (i.e., LLN ≤ creatinine ≤ ULN) at baseline were excluded from analysis. 95% confidence interval (CI) was calculated using Wilson's score method. Percentage has been rounded off.
From baseline up to Week 25

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Naïve and Switch Cohorts: Percentage of Participants Requiring Dialysis at Baseline or Week 25 and Who Completed 24 Weeks of Treatment
Prazo: Baseline and Week 25
Participants were considered to be on dialysis at baseline or at Week 25 if dialysis occurred within 5 days prior to the first crovalimab administration or prior to the end date of the primary treatment period, respectively. The percentage of participants who required dialysis at baseline and Week 25 has been reported here. Percentages have been rounded off.
Baseline and Week 25
Naïve and Switch Cohorts: Percentage of Participants With Change From Baseline to Week 25 (After 24 Weeks on Treatment) on Dialysis Status (Yes/No)
Prazo: From baseline up to Week 25
Participants were considered as being on dialysis at baseline or at Week 25 if dialysis occurred within 5 days prior to the first crovalimab administration or prior to the end date of the primary treatment period, respectively. Percentages have been rounded off.
From baseline up to Week 25
Naïve and Switch Cohorts: Observed Value of Estimated Glomerular Filtration Rate (eGFR), as Calculated From Central Serum Creatinine
Prazo: Baseline, Weeks 2, 3, 4, 5, 7, 9, 11, 13, 17, 21, and 25
GFR is an index of kidney function that describes the flow rate of filtered fluid through the kidneys. It was categorized according to chronic kidney disease (CKD) staging criteria. eGFR was calculated using the creatinine-based bedside Schwartz equation. eGFR (milliliters per minute per 1.73 square meter [mL/min/1.73 m^2])=0.413*(height [ht]/serum creatinine [sCr]), if height is expressed in centimeters, or 41.3*(ht/sCr), if height is expressed in meters.
Baseline, Weeks 2, 3, 4, 5, 7, 9, 11, 13, 17, 21, and 25
Naïve and Switch Cohorts: Change From Baseline to Week 25 in eGFR, as Calculated From Central Serum Creatinine
Prazo: Baseline, Weeks 2, 3, 4, 5, 7, 9, 11, 13, 17, 21, and 25
GFR is an index of kidney function that describes the flow rate of filtered fluid through the kidneys. It was categorized according to CKD staging criteria. eGFR was calculated using the creatinine-based bedside Schwartz equation. eGFR (mL/min/1.73 m^2])=0.413*(ht/sCr), if height is expressed in centimeters, or 41.3*(ht/sCr), if height is expressed in meters.
Baseline, Weeks 2, 3, 4, 5, 7, 9, 11, 13, 17, 21, and 25
Naïve and Switch Cohorts: Percentage of Participants With Change From Baseline to Week 25 (After 24 Weeks on Treatment) in CKD Stage, as Assessed Based on eGFR Calculated From Central Serum Creatinine
Prazo: From baseline up to Week 25
CKD stage was assessed using eGFR, calculated from central serum creatinine using Creatinine-based bedside Schwartz equation & classified according to National Kidney Foundation CKD staging criteria as follows: G1 (≥90 mL/min/1.73 m²; normal or high kidney function), G2 (60-89 mL/min/1.73 m²; mildly decreased kidney function), G3a (45-59 mL/min/1.73 m²; mildly to moderately decreased kidney function), G3b (30-44 mL/min/1.73 m²; moderately to severely decreased kidney function), G4 (15-29 mL/min/1.73 m²; severely decreased kidney function), & G5 (<15 mL/min/1.73 m²; kidney failure). Change in CKD stage from baseline to Week 25 was categorized as improved (participants who improved in CKD stage from Baseline to Week 25 were based on the number of participants who completed 24 weeks and were not Stage 1 at baseline), stable (no change), or worsened (participants with CKD Stage 1 to 4 at baseline) among participants who completed 24 weeks of treatment. Percentages have been rounded off.
From baseline up to Week 25
Naïve and Switch Cohorts: Observed Value of Platelet Count
Prazo: Baseline and Week 25
Baseline and Week 25
Naïve and Switch Cohorts: Observed Value of LDH
Prazo: Baseline and Week 25
Baseline and Week 25
Naïve and Switch Cohorts: Observed Value of Hemoglobin (Hb)
Prazo: Baseline and Week 25
Baseline and Week 25
Naïve and Switch Cohorts: Change From Baseline to Week 25 (After 24 Weeks on Treatment) in Platelet Count
Prazo: Baseline and Week 25
Baseline and Week 25
Naïve and Switch Cohorts: Change From Baseline to Week 25 (After 24 Weeks on Treatment) in LDH
Prazo: Baseline and Week 25
Baseline and Week 25
Naïve and Switch Cohorts: Change From Baseline to Week 25 (After 24 Weeks on Treatment) in Hb
Prazo: Baseline and Week 25
Baseline and Week 25
Naïve Cohort: Percentage of Participants With Platelet Count ≥ LLN at Two Separate Assessments, Obtained at Least 4 Weeks Apart (Minimum of 26 Days), by Week 25 (After 24 Weeks on Treatment)
Prazo: From baseline up to Week 25
This event was confirmed at two separate assessments obtained at least 4 weeks (a minimum of 26 days) apart and any measurement in between.
From baseline up to Week 25
Naïve Cohort: Percentage of Participants With LDH Normalization (i.e., ≤ ULN) at Two Separate Assessments, Obtained at Least 4 Weeks Apart (Minimum of 26 Days), by Week 25 (After 24 Weeks on Treatment)
Prazo: From baseline up to Week 25
Percentage has been rounded off.
From baseline up to Week 25
Naïve Cohort: Percentage of Participants With ≥ 25% Decrease in Serum Creatinine From Baseline, Confirmed at Two Separate Assessments, Obtained at Least 4 Weeks Apart (Minimum of 26 Days), by Week 25 (After 24 Weeks on Treatment)
Prazo: From baseline up to Week 25
Percentage has been rounded off.
From baseline up to Week 25
Naïve Cohort: Time to cTMAr
Prazo: From baseline up to Week 25
cTMAr was defined by meeting all of the following criteria at two separate assessments, obtained at least 4 weeks (a minimum of 26 days) apart, and any measurement in between: Platelet count ≥ LLN; LDH ≤ ULN; and ≥ 25% decrease in serum creatinine from baseline. Kalpan-Meier (K-M) method was used to estimate median time to cTMAr. Data for participants who did not reach cTMAr during PTP were censored at the date of their last visit when cTMAr was assessed during the primary treatment period or prior to the treatment discontinuation, whichever was earlier. Data for participants who received a prohibited therapy during the PTP were censored at the date of the first received prohibited therapy during the primary treatment period or prior to the treatment discontinuation, whichever was earlier.
From baseline up to Week 25
Naïve Cohort: Duration of cTMAr, Among Participants Who Achieved cTMAr
Prazo: From baseline up to primary CCOD (up to 190 weeks)
cTMAr=meeting following criteria at 2 separate assessments, obtained at least 4 weeks (minimum of 26 days) apart & any measurement in between: Platelet count ≥LLN; LDH ≤ULN; & ≥25% decrease in serum creatinine from baseline. Duration of cTMAr was calculated as time from start of cTMAr to end of cTMAr. End of cTMAr=when all of following criteria were met during same visit & confirmed at assessment that took place at least 4 weeks (minimum of 26 days) later: Platelet count <LLN; LDH >ULN; & ≥25% increase in serum creatinine from baseline & ULN. K-M method was used to estimate the median duration of cTMAr. Data for participants with no observed end of cTMAr at CCOD were censored at the date of their last visit when cTMAr was assessed before CCOD or before treatment discontinuation, whichever was earlier. Data for participants who received prohibited therapy before CCOD were censored at date of first receiving prohibited therapy or before treatment discontinuation, whichever was earlier.
From baseline up to primary CCOD (up to 190 weeks)
Naïve Cohort: Percentage of Participants With cTMAr Ongoing at Week 25
Prazo: At Week 25
cTMAr at Week 25 was defined by meeting all of the three cTMAr criteria at Week 25: Platelet count ≥ LLN; LDH ≤ ULN; and ≥ 25% decrease in serum creatinine from baseline. Percentage has been rounded off.
At Week 25
Switch Cohort: Percentage of Participants With Maintained Thrombotic Microangiopathy Response Control (mTMAc) From Baseline Through Week 25 (After 24 Weeks on Treatment)
Prazo: From baseline up to Week 25
mTMAc was considered not maintained if all of the following criteria were met during one of the visits between baseline and Week 25, and were confirmed at an assessment that took place at least 4 weeks (a minimum of 26 days) later: Platelet count < LLN; LDH > ULN; and 25% increase in serum creatinine from baseline.
From baseline up to Week 25
All Cohorts: Number of Participants With Adverse Events (AEs)
Prazo: Up to approximately 8 years
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Up to approximately 8 years
All Cohorts: Number of Participants With Injection-site Reactions, Infusion-related Reactions, Hypersensitivity, Malignant Hypertension (Including Malignant Renal Hypertension), and Infections (Including Meningococcal Meningitis)
Prazo: Up to approximately 8 years
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Up to approximately 8 years
All Cohorts: Number of Participants With AEs Leading to Study Drug Discontinuation
Prazo: Up to approximately 8 years
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Up to approximately 8 years
Switch Cohort: Number of Participants With Clinical Manifestations of Drug-target-drug Complexes (DTDCs)
Prazo: Up to approximately 8 years
Crovalimab and eculizumab bind distinct epitopes on complement component C5, and formation of DTDCs comprising crovalimab, eculizumab, and C5 are formed when participants switch treatment. DTDCs will be characterized using size exclusion chromatography (SEC) coupled with enzyme-linked immunosorbent assay (ELISA).
Up to approximately 8 years
All Cohorts: Serum Concentrations of Crovalimab Over Time
Prazo: Up to approximately 8 years
Up to approximately 8 years
All Cohorts: Number of Participants With Anti-drug Antibodies (ADAs) to Crovalimab
Prazo: Up to approximately 8 years
Participants will be considered to be ADA positive if they were ADA negative at baseline but developed an ADA response following stuy drug exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples is at least 4-fold greater than the titer of the baseline sample (treatment-enhanced ADA response).
Up to approximately 8 years
All Cohorts: Observed Value of Total Complement Activity 50 (CH50), as Measured by Liposome Immunoassay (LIA)
Prazo: Up to approximately 8 years
Up to approximately 8 years
All Cohorts: Change From Baseline in CH50 Over Time, as Measured by LIA
Prazo: Up to approximately 8 years
Up to approximately 8 years
All Cohorts: Observed Value of Free Complement Component 5 (C5) Concentrations in Crovalimab-treated Participants
Prazo: Up to approximately 8 years
Up to approximately 8 years
All Cohorts: Change From Baseline in Free C5 Concentrations Over Time in Crovalimab-treated Participants
Prazo: Up to approximately 8 years
Up to approximately 8 years
All Cohorts: Observed Value of Total C5 Concentrations in Crovalimab-treated Participants
Prazo: Up to approximately 8 years
Up to approximately 8 years
All Cohorts: Change From Baseline in Total C5 Concentrations Over Time in Crovalimab-treated Participants
Prazo: Up to approximately 8 years
Up to approximately 8 years

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Hoffmann-La Roche

Colaboradores

Chugai Pharmaceutical

Investigadores

  • Diretor de estudo: Clinical Trials, Hoffmann-La Roche

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

17 de novembro de 2021

Conclusão Primária (Real)

4 de julho de 2025

Conclusão do estudo (Estimado)

19 de maio de 2029

Datas de inscrição no estudo

Enviado pela primeira vez

6 de julho de 2021

Enviado pela primeira vez que atendeu aos critérios de CQ

6 de julho de 2021

Primeira postagem (Real)

12 de julho de 2021

Atualizações de registro de estudo

Última Atualização Postada (Real)

9 de setembro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

17 de agosto de 2026

Última verificação

1 de agosto de 2026

Mais Informações

Termos relacionados a este estudo

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • BO42354
  • 2023 (Concessão/Contrato do NIH dos EUA: GRAMMY Museum Foundation)
  • 2020-002437-15 (Número EudraCT)
  • 2023-505638-82-00 (Ctis)

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

SIM

Descrição do plano IPD

Pesquisadores qualificados podem solicitar acesso aos dados individuais do paciente por meio da plataforma de solicitação de dados de estudos clínicos (www.vivli.org). Mais detalhes sobre os critérios da Roche para estudos elegíveis estão disponíveis aqui (https://vivli.org/ourmember/roche/). Para obter mais detalhes sobre a Política Global da Roche sobre o Compartilhamento de Informações Clínicas e como solicitar acesso a documentos de estudos clínicos relacionados, consulte aqui (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Sim

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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