Efficacy of INM004 in Children With STEC-HUS

Phase 3

Recruiting

• Conditions: Hemolytic-Uremic Syndrome
• Interventions: Other: Placebo; Biological: INM004

• Registration Number: NCT06389474
• Lead Sponsor: Inmunova S.A.

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).

Detailed Description

The primary objective will be to evaluate the efficacy of INM004, added to the standard of care, as a treatment for STEC-HUS in the amelioration of renal function.

Secondary objectives

* To evaluate the efficacy of INM004 in the reduction of mortality.

* To evaluate the efficacy of INM004 in the prevention and reduction of extrarenal complications.

* To evaluate the efficacy of INM004 in the improvement of TMA laboratory parameters.

* To evaluate the efficacy of INM004 in the reduction of hospital stay days.

* To evaluate the safety of INM004

* To evaluate the pharmacokinetics of INM004

* To evaluate the kinetics of Stx

Study Timeline

• Study First Submitted: 2024-04-25
• Study First Submitted QC: 2024-04-25
• Study First Posted: 2024-04-29
• Study Start: 2024-10-05
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-21
• Last Update Posted: 2025-02-25
• Primary Completion: 2025-07-28
• Study Completion: 2025-09-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

1. Age ≥ 9 months and < 18 years at the time of randomization.

2. In addition, only for subjects < 1 year and ≥ 15 years, confirmation of STEC infection determined by:

   1. Detection of generic Stx, Stx1, Stx2, or Stx1/Stx2 in stools by enzyme immunoassay (EIA); or
   2. Detection of stx, stx1, stx2, or stx1/stx2 genes in stools by Polymerase Chain Reaction (PCR); or
   3. Detection of specific anti-polysaccharide (IgM) antibodies in serum; or
   4. Fecal culture positive for E. coli O157 confirmed by serogroup-specific seroagglutination.

3. Hospitalization at the participating institution.

4. History of onset of diarrhea within 10 days prior to STEC-HUS diagnosis at the participating institution.

5. Diagnosis of STEC-HUS defined as a subject with signs of renal damage, hemolysis, and platelet consumption:

   1. 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.

   2. Presence of hemolysis documented by:

      • LDH levels above the ULN for age, and/or
      • Presence of schistocytes in peripheral blood smear.

   3. Platelet consumption according to any of the following laboratory criteria:

      • Peripheral blood platelet count < 150 × 103/μL, and/or
      • A ≥50% decrease in peripheral blood platelet count compared to a sample collected within the previous 24 hours.

6. Informed consent form signed and dated by the subject or, the legal guardian(s), with the subject's assent as appropriate based on age and regulatory guidelines in the region.

7. Subjects who have already had menarche must have a negative pregnancy test.

Exclusion Criteria

1. Start of dialysis within 48 hours prior to admission to the participating institution.

2. More than 24 hours from diagnosis of STEC-HUS at the participating institution up to randomization.

3. History of chronic/recurrent hemolytic anemia, thrombocytopenia, or CKD.

4. Personal and/or family history of atypical HUS.

5. Suspected HUS secondary to infectious processes other than gastrointestinal (e.g., Streptococcus pneumoniae, HIV).

6. Suspected HUS secondary to other etiologies (e.g., drug-associated HUS, neoplasms, bone marrow or solid organ transplantation, autoimmune disorders).

7. 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.

8. 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.

9. Pregnant or breastfeeding woman.

10. Impossibility of hospitalization in the participating institution.

11. Concurrent participation in another clinical trial or having participated in a clinical trial in the last 3 months.

12. Severe malnutrition. Defined when the weight is three standard deviations below the median, according to height, age and sex as per WHO guidelines.

13. 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.
    • Trisomy 21.
    • Prematurity (born before 28 weeks gestation).
    • Other (according to investigator criteria).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Two doses of saline solution, 24 hours apart.
INM004	INM004	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.

Primary Outcome Measures

Name	Time	Method
Time to recovery of renal function during the acute phase	28 days	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.

Secondary Outcome Measures

Name	Time	Method
Short-term recovery of renal function	90 days	Proportion of subjects with a glomerular filtration rate ≥ lower limit of normal (according to age, height and sex) and serum creatinine ≤ upper limit of normal (according to age and sex), both measured in the absence of dialysis.
Dialysis requirement	90 days	Proportion of subjects requiring dialysis after 24 hours post-randomization
MAKE 90	90 days	Proportion of subjects meeting any of the following criteria at day 90: death, dialysis requirement after 24 hours post-randomization, dialysis of more than 10 days, or persistent decline in renal function (without recovery of glomerular filtration rate according to age, height, and sex).
Mortality	90 days	Proportion of subjects who die from any cause.
Dialysis longer than 10 days	90 days	Proportion of dialyzed subjects requiring more than 10 days of dialysis

Trial Locations

Locations (37)

Hospital Interzonal Dr. José Penna; 🇦🇷 Bahia Blanca, Buenos Aires, Argentina

Hospital de niños Sor María Ludovica; 🇦🇷 La Plata, Buenos Aires, Argentina

Clinica del niño y la madre; 🇦🇷 Mar Del Plata, Buenos Aires, Argentina

Hospital Interzonal Especializado Materno Infantil Don Victorio Tetamanti; 🇦🇷 Mar Del Plata, Buenos Aires, Argentina

Sanatorio Anchorena; 🇦🇷 Caba, Ciudad Autónoma De Buenos Aires, Argentina

Sanatorio Güemes; 🇦🇷 Ciudad Autonoma De Buenos Aires, Ciudad Autónoma De Buenos Aires, Argentina

Hospital de Pediatría S.A.M.I.C. "Prof. Dr. Juan P. Garrahan"; 🇦🇷 Ciudad Autonoma De Buenos Aires, Ciudad Autónoma De Buenos Aires, Argentina

Hospital General de Niños Pedro de Elizalde; 🇦🇷 Ciudad Autonoma De Buenos Aires, Ciudad Autónoma De Buenos Aires, Argentina

Hospital "San Antonio de Padua" Río Cuarto; 🇦🇷 Río Cuarto, Córdoba, Argentina

Hospital Teodoro J. Schestakow; 🇦🇷 San Rafael, Mendoza, Argentina

Hospital de Niños Zona Norte "Dr. Roberto M. Carra"; 🇦🇷 Rosario, Santa Fe, Argentina

Sanatorio de Niños; 🇦🇷 Rosario, Santa Fe, Argentina

Hospital De Clínicas Pte. Nicolás Avellaneda; 🇦🇷 San Miguel De Tucumán, Tucumán, Argentina

Clínica Zabala; 🇦🇷 Ciudad Autonoma de Buenos Aire, Argentina

Hospital de Niños Dr. Ricardo Gutierrez; 🇦🇷 Ciudad Autonoma de Buenos Aire, Argentina

Hospital Privado Centro Médico de Córdoba; 🇦🇷 Córdoba, Argentina

Hospital de Niños de la Santísima Trinidad; 🇦🇷 Córdoba, Argentina

Sanatorio Allende; 🇦🇷 Córdoba, Argentina

Hospital Pediátrico Dr. Humberto Notti; 🇦🇷 Mendoza, Argentina

Clínica Pediátrica San Lucas; 🇦🇷 Neuquén, Argentina

Hospital Público Materno Infantil; 🇦🇷 Salta, Argentina

Hospital Pediátrico San Luis; 🇦🇷 San Luis, Argentina

Cliniques universitaires Saint-Luc; 🇧🇪 Brussel, Belgium

CHU De Bordeaux; 🇫🇷 Bordeaux, France

Hospices Civils De Lyon - Hopital Femme Mere Enfant; 🇫🇷 Lyon, France

Centre Hospitalier Universitaire De Montpellier; 🇫🇷 Montpellier, France

Hospital Necker Enfants Malades; 🇫🇷 Paris, France

Robert Debre University Hospital; 🇫🇷 Paris, France

Trousseau Hospital; 🇫🇷 Paris, France

University Medical Center Hamburg-Eppendorf; 🇩🇪 Hamburg, Germany

Universitaetsklinikum Heidelberg AöR; 🇩🇪 Heidelberg, Germany

Children's Health Ireland; 🇮🇪 Dublin, Ireland

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico; 🇮🇹 Milano, Italy

Spitalul Clinic De Urgenta Pentru Copii Cluj-Napoca; 🇷🇴 Cluj-Napoca, Romania

Bristol Royal Hospital for Children; 🇬🇧 Bristol, United Kingdom

Royal Hospital for Sick Children; 🇬🇧 Glasgow, United Kingdom

Great Ormon Street Hospital for Children; 🇬🇧 London, United Kingdom