A Study to Assess Safety, Efficacy, and Pharmacokinetics of INM004 in Pediatric Patients With STEC-HUS

NCT05569746 | Completed Phase 2 DMC

• 1 other identifier: CT-INM004-03
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 16

Brief Summary

Hemolytic Uremic Syndrome (HUS) is a foodborne disease which mainly affects children. It is caused by Escherichia coli bacteria, which release a toxin called Shiga toxin within the body. This infectious form of HUS, defined as STEC-HUS, can cause sporadic cases or outbreaks, as observed in different countries. Argentina has the highest incidence of STEC-HUS worldwide. The disease is endemic, representing approximately 95% of all HUS cases nationwide. STEC-HUS generally begins with diarrhea (with or without blood), and can also cause fever, abdominal pain, and cramps. Then the child may have pallor, altered consciousness, decreased urine output, seizures, and other symptoms. Although death is uncommon (it occurs in 2-4% of cases), it is a very serious disease that mainly affects the kidneys, and also other organs such as the brain. About half of children need to undergo a risky procedure such as dialysis (due to malfunctioning kidneys); and most of them also receive blood transfusions. Around 30% of the patients are left with lifelong consequences that can range from permanent kidney damage to the need for a transplant. So far there is no drug, antibiotic or vaccine to prevent or treat HUS. Current treatment protocols include hospitalization for all patients with HUS, and supportive therapy such as hydration and salt intake. Support therapy is not a specific treatment, but rather helps the body better defend itself against the disease. The purpose of this study is to establish whether it is safe and effective to treat patients who are diagnosed with STEC-HUS, with INM004 (study drug). INM004 is an investigational product "Fraction F(ab')2 of Equine Shiga Antitoxin Immunoglobulin". It is a concentrated and sterile serum obtained from healthy horses immunized against Shiga toxin that contains antibodies capable of neutralizing it. The initial hypothesis is that INM004 would neutralize the entry of Shiga toxin into the body's cells thus preventing the consequent toxic damage. With the proposed treatment, INM004 would eliminate the Shiga toxin, preventing the progression of HUS symptoms and its serious complications (such as the need for and duration of dialysis, duration of hospital stays, as well as neurological, cardiovascular, intestinal complications, among others) which are associated with high morbidity and mortality. This treatment could then have an impact in health costs of STEC-HUS as well as the social costs.

Conditions

Diarrhea-Associated Hemolytic Uremic Syndrome; Pediatric Kidney Disease; Hemolytic-Uremic Syndrome

Keywords

STEC-HUS

Outcome Measures

Primary Outcomes (3)

• Days of dialysis

  Days of dialysis recorded as a continuous variable from 0 to 28 days

  28 days

• Adverse events (AEs)

  Incidence of AEs classified according to affected organ systems and according to severity Incidence of AEs of special interest: incidence of injection site reactions and hypersensitivity reactions (ie, allergic reaction, anaphylaxis, and serum sickness).

  28 days

• Pharmacokinetics (PK) Evaluation of INM004

  Serum concentration of INM004 at different time intervals in subjects participating in this substudy

  0, 1, 24, 26, 48 and 120 hours post-dose

Secondary Outcomes (29)

• Mortality

  28 days

• Change in thrombotic microangiopathy involvement (Creatinine %)

  28 days

• Change in thrombotic microangiopathy involvement (Creatinine)

  28 days

• Change in thrombotic microangiopathy involvement (Hematuria %)

  28 days

• Change in thrombotic microangiopathy involvement (Hematuria)

  28 days

Study Arms (1)

INM004

EXPERIMENTAL

2 doses of 4 mg/kg separated by 24 h

Drug: INM004; Other: SoC

Interventions

INM004 DRUG

Two 4 mg/kg doses of INM004, 24 h (±2 h) apart, will be assessed. Each dose will be administered as an intravenous infusion during 50 min.

Also known as: Equine immunoglobulin fragment F(ab')2 anti-Shiga toxin

INM004

SoC OTHER

Standard of care

INM004

Eligibility Criteria

• Age: 1 Year - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age: ≥1 and \<12 years.
• With hospitalization criterion in the participating facility.
• Clinical event with a diagnosis compatible with STEC-HUS defined as:
• Presence of signs of kidney injury defined as:
• Serum creatinine value above the UNL for age and sex, and/or
• Hematuria (≥5 red blood cells per field or ≥27 red blood cells/μL in urine sediment),
• And at least 1 of the following 2 criteria:
• Presence of hemolysis documented by: LDH levels above the UNL for age, and/or presence of schistocytes in peripheral blood smears.
• Platelet consumption according to any of the following laboratory criteria: Platelet count \<150 × 103/μl, in peripheral blood, and/or ≥50% decrease in peripheral blood platelet count compared to the baseline sample or within the previous 24 h.
• Onset of diarrhea no more than 13 days at the time of diagnosis of a condition compatible with STEC-HUS at the participating facility.
• For the treatment group, informed consent form signed and dated by the parent(s) or legal guardian with the assent of the subject as appropriate based on age and regulatory guidelines.
• For the treatment group, female girls/adolescents who are already fertile must have a negative pregnancy test. Note: They will be considered fertile when they have already had menarche.

You may not qualify if:

• With dialysis for more than 48 h at the time of diagnosis of a condition compatible with STEC-HUS in the participating facility.
• History of chronic/recurrent hemolytic anemia, thrombocytopenia, or chronic renal failure.
• Personal and/or family history of atypical HUS.
• Suspected HUS secondary to other infectious processes not from gastrointestinal origin.
• Evidence of clinically significant chronic active disease that is not medically controlled whose symptoms/signs may interfere with the treatment/diagnosis of this study, in the opinion of the investigator.
• For the interventional group, history of: a) anaphylaxis of any type; b) previous administration of equine serum (for example, anti-venom serum, anti-spider toxin serum, anti-SARS-CoV-2 serum, etc.) or an allergic reaction from contact or exposure to horses.
• Pregnant or lactating women.
• For the interventional group, the impossibility of hospitalization in the participating institution.

Sponsors & Collaborators

• Inmunova S.A.: lead
• KLIXAR: collaborator
• Linical Co., Ltd.: collaborator
• PHV LATAM: collaborator

Study Sites (16)

Hospital Interzonal Dr. José Penna

Bahía Blanca, Buenos Aires, 8000, Argentina

Location

Hospital De Niños Sor María Ludovica

La Plata, Buenos Aires, Argentina

Location

Hospital Interzonal Especializado Materno Infantil Don Victorio Tetamanti

Mar del Plata, Buenos Aires, Argentina

Location

Hospital El Cruce - Néstor Kirchner

San Juan Bautista, Buenos Aires, Argentina

Location

Hospital Dr. Lucio Molas

Santa Rosa, La Pampa Province, Argentina

Location

Sanatorio de Niños

Rosario, Santa Fe Province, Argentina

Location

Hospital General de Niños Pedro de Elizalde

Buenos Aires, 1270, Argentina

Location

Clínica Zabala Swiss Medical

Buenos Aires, Argentina

Location

Hospital de Pediatría Garrahan

Buenos Aires, Argentina

Location

Hospital Italiano de Buenos Aires

Ciudad Autonoma de Buenos Aire, 1199, Argentina

Location

Hospital de Niños Dr. Ricardo Gutierrez

Ciudad Autonoma de Buenos Aire, Argentina

Location

Sanatorio Güemes

Ciudad Autonoma de Buenos Aire, Argentina

Location

Hospital de Niños de la Santísima Trinidad

Córdoba, Argentina

Location

Sanatorio Allende

Córdoba, Argentina

Location

Hospital Pediátrico Dr. Humberto Notti

Mendoza, Argentina

Location

Hospital Provincial Neuquén Dr. Eduardo Castro Rendón

Neuquén, Argentina

Location

MeSH Terms

Conditions

Hemolytic-Uremic Syndrome

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

Study Officials

• Fernando Goldbaum, PhD

  Inmunova S.A.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A Phase II, multicenter, controlled study, with a prospective open "treatment group" (with INM004 added to Standard of Care) and a retrospective "control group" (only treated with Standard of Care).

Study Record Dates

• First Submitted: August 22, 2022
• First Posted: October 6, 2022
• Study Start: October 6, 2022
• Primary Completion: May 15, 2023
• Study Completion: July 14, 2023
• Last Updated: August 21, 2023

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

AR (16)