Efficacy of INM004 in Children With STEC-HUS

NCT06389474 | Recruiting Phase 3 DMC

• 1 other identifier: CT-INM004-04
• Study Type: interventional
• Target: 220
• Locations: 9 countries
• Sites: 52

Brief Summary

The objectives of this study are to evaluate the efficacy, safety, and pharmacokinetics of INM004 in pediatric patients with Hemolytic Uremic Syndrome associated to infection by Shiga toxin-producing Escherichia coli (STEC-HUS).

Conditions

Hemolytic-Uremic Syndrome

Keywords

STEC-HUS; Typical Hemolytic Uremic Syndrome; Diarrhea asociated-Hemolytic Uremic Syndrome; Shiga toxin-producing Escherichia coli; Shiga toxin

Outcome Measures

Primary Outcomes (1)

• Time to recovery of renal function during the acute phase

  Time (days) to achieve a glomerular filtration rate greater than or equal to the lower limit of normal (according to age, height, and sex) and a serum creatinine lower than or equal to the upper limit of normal (according to age and sex), both measured in the absence of dialysis.

  28 days

Secondary Outcomes (5)

• Short-term recovery of renal function

  90 days

• MAKE 90

  90 days

• Dialysis longer than 10 days

  90 days

• Dialysis requirement

  90 days

• Mortality

  90 days

Other Outcomes (23)

• CKD Risk Assessment According to Kidney Disease Improving Global Outcomes (KDIGO) Categories

  90 days

• Evolution of renal function at 7 days (GFR_AUC1-7)

  7 days

• Evolution of renal function at 28 days (GFR_AUC1-28)

  28 days

Study Arms (2)

INM004

EXPERIMENTAL

Two doses of Anti-Shiga Toxin Hyperimmune Equine Immunoglobulin F(ab´)2 fragment at a dosage of 4 mg/kg of body weight, 24 hours apart.

Biological: INM004

Placebo

PLACEBO COMPARATOR

Two doses of saline solution, 24 hours apart.

Other: Placebo

Interventions

INM004 BIOLOGICAL

Two doses of Anti-Shiga Toxin Hyperimmune Equine Immunoglobulin F(ab´)2 fragments at a dosage of 4 mg/kg of body weight, 24 hours apart. Each vial contains 25 mg of protein/ml. Therefore, each subject must receive 0.16 ml/kg per dose. The vial volume will be reconstituted in a 100 ml (for subjects with a body weight of 20 kg or more) or 50 ml (for subjects under 20 kg of body weight) infusion bag. It will be administered as an intravenous infusion using an infusion pump over a period of 50 minutes. In subjects with a BMI over 30 kg/m2, infusion will be performed over a period of 100 minutes

Also known as: Active

INM004

Placebo OTHER

Two doses of placebo, 24 hours apart. The placebo solution has the same composition of excipients as INM004 without the active pharmaceutical ingredient, and its appearance is identical. Each subject must receive 0.16 ml/kg of placebo solution per dose. The vial volume will be reconstituted in a 100 ml (for subjects with a body weight of 20 kg or more) or 50 ml (for subjects under 20 kg of body weight) infusion bag. It will be administered as an intravenous infusion using an infusion pump over a period of 50 minutes. In subjects with a BMI over 30 kg/m2, infusion will be performed over a period of 100 minutes

Also known as: Control

Placebo

Eligibility Criteria

• Age: 9 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age ≥ 9 months and \< 18 years at the time of randomization.
• In addition, only for subjects \< 1 year and ≥ 15 years, confirmation of STEC infection determined by:
• Detection of generic Stx, Stx1, Stx2, or Stx1/Stx2 in stools by enzyme immunoassay (EIA); or
• Detection of stx, stx1, stx2, or stx1/stx2 genes in stools by Polymerase Chain Reaction (PCR); or
• Detection of specific anti-polysaccharide (IgM) antibodies in serum; or
• Fecal culture positive for E. coli O157 confirmed by serogroup-specific seroagglutination.
• Hospitalization at the participating institution.
• History of onset of diarrhea within 10 days prior to STEC-HUS diagnosis at the participating institution.
• Diagnosis of STEC-HUS defined as a subject with signs of renal damage, hemolysis, and platelet consumption:
• Signs of renal damage defined as:
• Serum creatinine value above the ULN for age and sex, and GFR below the LLN for age, sex, and height.
• Presence of hemolysis documented by:
• LDH levels above the ULN for age, and/or
• Presence of schistocytes in peripheral blood smear.
• Platelet consumption according to any of the following laboratory criteria:

You may not qualify if:

• Start of dialysis within 48 hours prior to admission to the participating institution.
• More than 24 hours from diagnosis of STEC-HUS at the participating institution up to randomization.
• History of chronic/recurrent hemolytic anemia, thrombocytopenia, or CKD.
• Personal and/or family history of atypical HUS.
• Suspected HUS secondary to infectious processes other than gastrointestinal (e.g., Streptococcus pneumoniae, HIV).
• Suspected HUS secondary to other etiologies (e.g., drug-associated HUS, neoplasms, bone marrow or solid organ transplantation, autoimmune disorders).
• Any other acute or chronic medical condition that, in the opinion of the investigator, may interfere with the evaluation of the efficacy and/or safety of the study medication.
• History of: a) anaphylaxis of any kind; b) prior administration of equine serum (e.g., antivenom, anti-arachnid serum, anti-SARS-CoV-2 serum, etc.) or an allergic reaction from contact or exposure to horses.
• Pregnant or breastfeeding woman.
• Impossibility of hospitalization in the participating institution.
• Concurrent participation in another clinical trial or having participated in a clinical trial in the last 3 months.
• Severe malnutrition. Defined when the weight is three standard deviations below the median, according to height, age and sex as per WHO guidelines.
• Medical conditions that may affect kidney function or cause/enhance neurological symptoms or signs:
• Congenital or acquired anomalies that may affect functioning renal mass.
• Epilepsy or structural abnormalities of the brain that may increase the risk of seizures.

Sponsors & Collaborators

• Inmunova S.A.: lead
• Exeltis: collaborator
• Chemo Research: collaborator
• Linical: collaborator
• KLIXAR: collaborator

Study Sites (52)

Hospital Interzonal Dr. José Penna

Bahía Blanca, Buenos Aires, 8000, Argentina

NOT YET RECRUITING

Hospital Penna

Bahía Blanca, Buenos Aires, Argentina

NOT YET RECRUITING

Hospital de niños Sor María Ludovica

La Plata, Buenos Aires, 1900, Argentina

RECRUITING

Clinica del niño y la madre

Mar del Plata, Buenos Aires, 7600, Argentina

RECRUITING

Hospital Interzonal Especializado Materno Infantil Don Victorio Tetamanti

Mar del Plata, Buenos Aires, Argentina

RECRUITING

Sanatorio de la Trinidad Ramos Mejia

Ramos Mejía, Buenos Aires, Argentina

NOT YET RECRUITING

Hospital El Cruce

San Juan Bautista, Buenos Aires, Argentina

NOT YET RECRUITING

Sanatorio Güemes

Buenos Aires, Buenos Aires F.D., 1188, Argentina

ACTIVE NOT RECRUITING

Hospital de Pediatría S.A.M.I.C. "Prof. Dr. Juan P. Garrahan"

Buenos Aires, Buenos Aires F.D., 1245, Argentina

RECRUITING

Hospital General de Niños Pedro de Elizalde

Buenos Aires, Buenos Aires F.D., 1270, Argentina

ACTIVE NOT RECRUITING

Sanatorio Anchorena

CABA, Buenos Aires F.D., 1425, Argentina

ACTIVE NOT RECRUITING

Hospital Privado Centro Médico de Córdoba

Córdoba, Córdoba Province, 5016, Argentina

RECRUITING

Hospital de Niños de la Santísima Trinidad

Córdoba, Córdoba Province, Argentina

RECRUITING

Hospital "San Antonio de Padua" Río Cuarto

Río Cuarto, Córdoba Province, 5806, Argentina

RECRUITING

Hospital Pediátrico Dr. Humberto Notti

Mendoza, Mendoza Province, Argentina

RECRUITING

Hospital Teodoro J. Schestakow

San Rafael, Mendoza Province, 5600, Argentina

RECRUITING

Clínica Pediátrica San Lucas

Neuquén, Neuquén Province, 8300, Argentina

SUSPENDED

Hospital Público Materno Infantil

Salta, Salta Province, 4400, Argentina

RECRUITING

Hospital Pediátrico San Luis

San Luis, San Luis Province, 5700, Argentina

RECRUITING

Hospital de Niños Zona Norte "Dr. Roberto M. Carra"

Rosario, Santa Fe Province, 2013, Argentina

RECRUITING

Sanatorio de Niños

Rosario, Santa Fe Province, Argentina

RECRUITING

Hospital De Clínicas Pte. Nicolás Avellaneda

San Miguel de Tucumán, Tucumán Province, 4001, Argentina

ACTIVE NOT RECRUITING

Clínica Zabala

Ciudad Autonoma de Buenos Aire, Argentina

ACTIVE NOT RECRUITING

Hospital de Niños Dr. Ricardo Gutierrez

Ciudad Autonoma de Buenos Aire, Argentina

RECRUITING

Sanatorio Allende

Córdoba, Argentina

WITHDRAWN

Cliniques universitaires Saint-Luc

Brussels, Belgium

ACTIVE NOT RECRUITING

CHU De Bordeaux

Bordeaux, France

ACTIVE NOT RECRUITING

Hospices Civils De Lyon - Hopital Femme Mere Enfant

Lyon, France

RECRUITING

Centre Hospitalier Universitaire De Montpellier

Montpellier, France

ACTIVE NOT RECRUITING

CHU Nantes

Nantes, France

NOT YET RECRUITING

Hospital Necker Enfants Malades

Paris, France

ACTIVE NOT RECRUITING

Robert Debre University Hospital

Paris, France

RECRUITING

Trousseau Hospital

Paris, France

ACTIVE NOT RECRUITING

CHU Rouen

Rouen, France

NOT YET RECRUITING

Charité - Universitätsmedizin Berlin

Berlin, Germany

NOT YET RECRUITING

University Hospital Cologne AöR

Cologne, Germany

NOT YET RECRUITING

Universitaetsklinikum Heidelberg AöR

Heidelberg, Germany

RECRUITING

Children's Health Ireland

Dublin, Ireland

ACTIVE NOT RECRUITING

University Hospital Consorziale Policlinico

Bari, Italy

RECRUITING

IRCCS Sant'Orsola

Bologna, Italy

NOT YET RECRUITING

Istituto Gianina Gaslini

Genova, Italy

RECRUITING

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, Italy

RECRUITING

Azienda Ospedale Università

Padua, Italy

NOT YET RECRUITING

Spitalul Clinic de Urgenta pentru Copii Marie Sklodowska Curie

Bucharest, Romania

NOT YET RECRUITING

Spitalul Clinic De Urgenta Pentru Copii Cluj-Napoca

Cluj-Napoca, Romania

RECRUITING

Spitalul Clinic de Urgenta pentru Copii Louis Turcanu

Timișoara, Romania

NOT YET RECRUITING

Hospital Universitario De Cruces

Barakaldo, Spain

RECRUITING

Hospital Infantil Universitario Niño Jesus

Madrid, Spain

RECRUITING

Hospital Universitario 12 De Octubre

Madrid, Spain

RECRUITING

Bristol Royal Hospital for Children

Bristol, United Kingdom

NOT YET RECRUITING

Royal Hospital for Sick Children

Glasgow, G51 4TF, United Kingdom

RECRUITING

Great Ormon Street Hospital for Children

London, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Hemolytic-Uremic Syndrome

Interventions

Exercise

Condition Hierarchy (Ancestors)

Uremia; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Santiago Sanguineti, Ph.D

  Inmunova S.A.

  STUDY DIRECTOR

Central Study Contacts

Mariana Colonna, Bioch

CONTACT

+541120331455; mcolonna@inmunova.com

Ana Perez

CONTACT

ana.perez@exeltis.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Adaptive design. IA will be done when approximately 50% of the enrollment is reached and the participants have completed 28 days of follow-up. This analysis will not be blinded and will be carried out to declare futility or re-estimate the sample size. The re-estimation of the sample size will allow a maximum of 300 randomized subjects in total, but a reduction in the initial item size of 220 subjects is not expected. In case of re-estimating the sample size, the smallest sample size under 300 will be selected, which allows a power of ≥ 80%. %. If with 300 subjects, a power of 80% is not reached, but it is ≥ 50%, then the sample size is re-estimated to 300 subjects, as long as the conditional power of the IA is ≥ 50% (promising results)

Study Record Dates

• First Submitted: April 25, 2024
• First Posted: April 29, 2024
• Study Start: October 5, 2024
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 15, 2026

Record last verified: 2026-01

Locations

FR (8); IE (1); IT (5); BE (1); AR (25); RO (3); GB (3); ES (3); DE (3)