Anti-Shiga Toxin Hyperimmune Equine Immunoglobulin F(ab')2 Fragment (INM004) in Healthy Volunteers
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Stage I - Drug: INM004 Dose 1
|
Biological: Drug: INM004 Dose 1
Stage I- Cohort I: (2mg/kg) administered at a single dose. The ratio is 3:1 (investigational product:placebo) -
|
| Placebo Comparator: Stage I - Placebo Dose 1
|
Other: Placebo
A placebo infusion will be administered at the same infusion rate as the Drug arm
|
| Experimental: Stage I- Drug: INM004 Dose 2
|
Biological: Drug: INM004 Dose 2
Stage I- Cohort II: Dose 2 (4mg/kg) administered at a single dose. The ratio is 3:1 (investigational product:placebo)
|
| Placebo Comparator: Stage I- Placebo Dose 2
|
Other: Placebo
A placebo infusion will be administered at the same infusion rate as the Drug arm
|
| Experimental: Stage II- Drug: INM004 Repeated Dose
|
Biological: Drug: INM004- Repeated dose
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).
|
| Placebo Comparator: Stage II- Placebo Repeated Dose
|
Other: Placebo
A placebo infusion will be administered at the same infusion rate as the Drug arm
|
Outcome Measures
Primary Outcome Measures
- 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
- Number of participants with treatment-related hypersensitivity events as assessed by CTCAE v4.0 [4 weeks]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Body mass index: between 19 and 27.
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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.
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Women of child-bearing potential using at least two barrier birth control methods.
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Sexually active men using medically accepted birth control methods, such as condom with spermicide.
Exclusion Criteria:
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Known hypersensitivity to equine serum.
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Hypersensitivity to any of the components of the pharmaceutical preparation.
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History of severe allergic reactions to any type of antigen.
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History of mental illness.
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Participation in another clinical research study within 90 days6 months prior to the start of this study
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History of alcohol or drug abuse.
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History or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, hematological, neurological disease.
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Having received contrast substances for radiological studies of any kind in the two weeks prior to the start of the study.
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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.
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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
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Having given blood within a period of under 2 months prior to the start of the study
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Documented infection with HIV, hepatitis B and/or hepatitis C.
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Pregnancy
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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.
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History of vaccination within the month prior to the start of the study.
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Infectious disease requiring hospitalization within the month prior to the inclusion in the study.
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Having received a transfusion of blood products within three months prior to the inclusion in the study
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Having received any medication within 14 days prior to the inclusion in the study.
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Family relation or work relation to the personnel of the research group.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital Italiano de Buenos Aires | Ciudad Autónoma de Buenos Aire | Argentina |
Sponsors and Collaborators
- Inmunova S.A.
- Hospital Italiano de Buenos Aires
Investigators
- Study Director: Santiago Sanguineti, Ph.D, Inmunova S.A.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CT-INM004-01