Anti-Shiga Toxin Hyperimmune Equine Immunoglobulin F(ab')2 Fragment (INM004) in Healthy Volunteers

Study Overview
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Brief Summary
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This is Prospective Randomized Placebo controlled Single Blind Phase I study to evaluate the safety, tolerance and pharmacokinetics of the anti-Shiga toxin hyperimmune equine immunoglobulin F(ab')2 fragment (INM004) in healthy volunteers.

Detailed Description
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This is a study that will be conducted at a single site in Argentina to characterize the Pharmacokinetics (PK) profile, safety and tolerability of anti-Shiga toxin hyperimmune equine immunoglobulin F(ab')2 fragment (INM004) in 14 healthy subjects. This is a dose escalation study. Subjects will receive a single dose of an infusion of the biological product or placebo in Stage I where 2 cohorts will be assessed with 2 different doses of INM004. Subjects will receive a repeated dose (3 doses total, every 24 hs) of an infusion of the biological product or placebo in Stage II. The total duration of study participation is 4 weeks for each subject. Subjects will complete a follow-up visit at Day 30 after the dosing. Study duration is expected to last 6 months. The investigational product intent to use is for the prevention of the development of Hemolytic Uremic Syndrome (HUS) associated to Shigatoxin producing Escherichia coli (STEC).

Official Title
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A Phase I Study to Evaluate the Safety, Tolerance and Pharmacokinetics of the Anti-Shiga Toxin Hyperimmune Equine Immunoglobulin F(ab')2 Fragment (INM004) in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Biological: Drug: INM004 Dose 1
* Biological: Drug: INM004 Dose 2
* Biological: Drug: INM004- Repeated dose
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index: between 19 and 27. Healthy subject, as determined by clinical exam, medical history and laboratory tests (chemistry, hematology and urine, pregnancy test if applicable) performed during the screening visit. Chest x-ray and electrocardiogram within normal ranges. -.Willing to participate and sign the informed consent. Women of child-bearing potential using at least two barrier birth control methods. Sexually active men using medically accepted birth control methods, such as condom with spermicide. Exclusion Criteria: Known hypersensitivity to equine serum. Hypersensitivity to any of the components of the pharmaceutical preparation. History of severe allergic reactions to any type of antigen. History of mental illness. Participation in another clinical research study within 90 days6 months prior to the start of this study History of alcohol or drug abuse. History or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, hematological, neurological disease. Having received contrast substances for radiological studies of any kind in the two weeks prior to the start of the study. Receiving or having received any prescription drug within the two weeks prior to the start of the study, including oral contraceptives in women of child-bearing potential. Having received more than three doses of any over-the-counter medication during the week prior to the start of the study or any medication within two days prior to the hospitalization Having given blood within a period of under 2 months prior to the start of the study Documented infection with HIV, hepatitis B and/or hepatitis C. Pregnancy History of asthma, allergy, prior administration of equine serum (por example, anti-tetanus serum or anti-ophidic serum or anti-arachnid toxin serum) or allergic reaction due to contact or exposure to horses. History of vaccination within the month prior to the start of the study. Infectious disease requiring hospitalization within the month prior to the inclusion in the study. Having received a transfusion of blood products within three months prior to the inclusion in the study Having received any medication within 14 days prior to the inclusion in the study. Family relation or work relation to the personnel of the research group.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stage I - Drug: INM004 Dose 1<br> | Biological: Drug: INM004 Dose 1<br>* Stage I- Cohort I: (2mg/kg) administered at a single dose. The ratio is 3:1 (investigational product:placebo) -<br>|
| Placebo Comparator: Stage I - Placebo Dose 1<br> | Other: Placebo<br>* A placebo infusion will be administered at the same infusion rate as the Drug arm<br>|
| Experimental: Stage I- Drug: INM004 Dose 2<br> | Biological: Drug: INM004 Dose 2<br>* Stage I- Cohort II: Dose 2 (4mg/kg) administered at a single dose. The ratio is 3:1 (investigational product:placebo)<br>|
| Placebo Comparator: Stage I- Placebo Dose 2<br> | Other: Placebo<br>* A placebo infusion will be administered at the same infusion rate as the Drug arm<br>|
| Experimental: Stage II- Drug: INM004 Repeated Dose<br> | Biological: Drug: INM004- Repeated dose<br>* Stage II: Either 3 doses of 2 mg/kg or 4 mg/kg will be administered every 24 hs. The ratio is 5:1 (investigational product : placebo).<br>|
| Placebo Comparator: Stage II- Placebo Repeated Dose<br> | Other: Placebo<br>* A placebo infusion will be administered at the same infusion rate as the Drug arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 |  | 4 weeks | 
| Maximum Plasma Concentration [Cmax] |  | 4 weeks | 
| Area Under the Curve [AUC] |  | 4 weeks | 
| Elimination half-life (t½) |  | 4 weeks | 
| Time of Maximum concentration observed (Tmax) |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related hypersensitivity events as assessed by CTCAE v4.0 |  | 4 weeks |