A Phase III study to evaluate the efficacy of INM004 (Shiga antitoxin) in pediatric patients with Shiga toxin-producing Escherichia coli-associated Hemolytic Uremic Syndrome.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Chemo Research S.L., Inmunova S.A.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

24 Jun 2025 → ongoing

Decision date (initial)

2024-10-07

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

Evaluate the efficacy of INM004, added to the SoC, in the amelioration of renal involvement.

Secondary objectives 7

1. To evaluate the efficacy of INM004 in the reduction of mortality
2. To evaluate the efficacy of INM004 in the prevention and reduction of extrarenal complications associated with STEC-HUS
3. To assess the efficacy of INM004 in improving the hematological parameters of MAT
4. To evaluate the efficacy of INM004 in reducing the number of days of hospital stay
5. To evaluate the safety of INM004
6. To evaluate the PK of INM004
7. To evaluate the kinetics of the Stx

Conditions and MedDRA coding

Hemolytic Uremic Syndrome

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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: a. Detection of generic Stx, Stx1, Stx2, or Stx1/Stx2 in stool by enzyme immunoassay (EIA); or b. Detection of stx, stx1, stx2, or stx1/stx2 genes in stool by Polymerase Chain Reaction (PCR); or c. Detection of specific anti-lipopolysaccharide (IgM) antibodies in whole blood or serum; or d. 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 the clinical diagnosis of STEC-HUS at the participating institution.
5. Clinical diagnosis of STEC-HUS defined as a subject with signs of renal damage, hemolysis and platelet consumption 1: a. Signs of renal damage defined as: - Serum creatinine value above the ULN for age and sex 2,3, and GFR below the LLN for age, sex and height. b. Presence of hemolysis documented by: - LDH levels above the ULN for age, and/or - Presence of schistocytes in peripheral blood smear. c. 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 of the region.
7. Subjects who have already had menarche (WOCBP) must have a negative highly sensitive urine or serum pregnancy test

Exclusion criteria 13

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 (such as acute infections, diabetes, liver disease requiring medical treatment, etc.)
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. Known medical conditions that may affect kidney function or cause/enhance neurological symptoms or signs such as: • Congenital or acquired structural anomalies of the urinary tract. • Epilepsy or structural abnormalities of the brain that may increase the risk of seizures. • Trisomy 21. • Prematurity (born before 28 weeks of gestation). • Other (according to the Investigator criteria)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to recovery of renal function during the acute phase. Defined as time (days) to achieve a GFR greater than or equal to the LLN (according to age, height, and sex) and a sCr less than or equal to the ULN (according to age and sex) measured in the absence of dialysis within the 28-day follow-up period.

Secondary endpoints 5

1. Recovery of kidney function at the short-term - Proportion of subjects with GFR ≥ LLN of reference (according to age, height, and sex) and sCr ≤ ULN of reference (according to age and sex) measured in the absence of dialysis, at day 90.
2. MAKE 90 - Proportion of subjects meeting any of the following criteria at day 90: death, dialysis requirement after 24 h post-randomization, dialysis for more than 10 days, or persistent decline in renal function (no recovery of expected GFR according to age, height, and sex).
3. Dialysis for more than 10 days - Proportion of dialyzed subjects requiring more than 10 days of dialysis.
4. Incidence of dialysis. - Proportion of subjects requiring dialysis after 24 h post-randomization.
5. Mortality. - Proportion of subjects who die due to any cause.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Chemo Research S.L.

Sponsor organisation

Chemo Research S.L.

Address

3rd Floor, Calle De Manuel Pombo Angulo 28 Calle De Manuel Pombo Angulo 28

City

Madrid

Postcode

28050

Country

Spain

Scientific contact point

Organisation

Chemo Research S.L.

Contact name

Enrico Colli

Public contact point

Organisation

Chemo Research S.L.

Contact name

Enrico Colli

Third parties 14

Inmunova S.A.

Sponsor organisation

Inmunova S.A.

Address

Paraguay 1535

City

Buenos Aires

Country

Argentina

Scientific contact point

Organisation

Inmunova S.A.

Contact name

Santiago Sanguineti

Public contact point

Organisation

Inmunova S.A.

Contact name

Santiago Sanguineti

Sponsor responsibilities

Article 77 compliance

Chemo Research S.L.

Contact point sponsor

Chemo Research S.L.

Article 77 implementation

Chemo Research S.L.

Locations

8 EU/EEA countries · 29 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 195 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications