Study of SAB-176 in Healthy Adult Participants

Study Overview
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Brief Summary
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Healthy adult participants will be challenged with the H1N1 Influenza virus and then treated with either SAB-176 or placebo.

Detailed Description
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Up to 60 eligible participants will be randomized in a 1:1 ratio to receive either SAB-176 (up to 25 mg/kg dose) or placebo. Healthy adult participants will be pre-screened for serosuitability for Influenza A/California/2009 H1N1 challenge virus. Serosuitable participants who sign the study specific informed consent form (ICF) will be challenged with an intranasal administration of Influenza A/California/2009 H1N1 virus on Day 0. Participants will be given intravenous (IV) infusion of SAB-176 or placebo on Day 1. Participants will be held in quarantine until Day 8.

Official Title
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A Phase 2a, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Safety and Treatment Efficacy of SAB-176 (a Quadrivalent Anti-seasonal Influenza Immunoglobulin Product) in an H1N1 Challenge Model in Healthy Adult Participants

Conditions
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Influenza A H1N1

Intervention / Treatment
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* Biological: SAB-176
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: An informed consent document signed and dated by the participant and the investigator Aged between 18 and 45 years on the day of signing the study specific ICF. In good health with no history, or current evidence, of clinically significant medical conditions, and no clinically significant test abnormalities that will interfere with participant safety, as defined by medical history, physical examination, (including vital signs), ECG, and routine laboratory tests as determined by the investigator. A documented medical history prior to enrollment. The following criteria are applicable to female participants: Females of childbearing potential must have a negative pregnancy test prior to enrollment. Females of non-childbearing potential: A.) Post-menopausal females: defined as having a history of amenorrhea for >12 months with no alternative medical cause, and/or by follicle stimulating hormone (FSH) level >40mIU/mL, confirmed by laboratory. b.) Documented status as being surgically sterile (e.g. tubal ligation, hysterectomy, bilateral salpingectomy, and bilateral oophorectomy). The following criteria apply to female and male participants: a.) Female participants of childbearing potential must use one form of highly effective contraception. Hormonal methods must be in place from at least 2 weeks prior to the first study visit. The contraception used must continue until 28 days after the date of dosing with IMP> Highly effective contraception is as described below: -Established use of hormonal methods of contraception described below (for a minimum of 2 weeks prior to the first study visit). When hormonal methods of contraception are used, male partners are required to use a condom with a spermicide: i.) Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: Oral, Intravaginal, or Transdermal ii.) progestogen-only hormonal contraception associated with inhibition of ovulation: Oral, Injectable, or Implantable b.) Intrauterine device c.) Intrauterine hormone-releasing system d.) bilateral tubal ligation e.) Male sterilization (with the appropriate post vasectomy documentation of the absence of sperm in the ejaculate) where the vasectomised male is the sole partner for that woman. f.) True abstinence - sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. B.) Male participants must agree to the contraceptive requirements below at entry to quarantine and continuing until 28 days after the date of dosing with IMP: Use a condom with a spermicide to prevent pregnancy in a female partner or to prevent exposure of any partner (male and female) to the IMP. Male sterilization with the appropriate post vasectomy documentation of the absence of sperm in in the ejaculate (please note that the use of condom with spermicide will still be required to prevent partner exposure). In addition, for female partners of childbearing potential, that partner must use another form of contraception such as one of the highly effective methods mentioned above for female participants. True abstinence - sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. C.) In addition to the contraceptive requirements above, male participants must agree not to donate sperm following discharge from quarantine until 28 days after the date of dosing with IMP. Serosuitable to the Challenge virus, as defined in the study Analytical Plan (AP). Exclusion Criteria: (Participants are excluded from the study if any of the following criteria apply) 1. History of, or currently active, symptoms or signs suggestive of upper or lower respiratory tract (LRT) infection within 4 weeks prior to the first study visit. 2. Any history or evidence of any other clinically significant or currently active systemic comorbidities including psychiatric disorders (includes participants with a history of depression and/or anxiety). And/or other major disease that, in the opinion of the investigator, may put the participant at undue risk, or interfere with a participant completing the stud and necessary investigations. The following conditions apply: Participants with clinically mild atopic eczema/atopic dermatitis and clinically mild psoriasis may be included at the Investigator's discretion (e.g., if small amounts of regular topical steroids are used, no eczema in cubital fossa; moderate to large amounts of daily dermal corticosteroids is an exclusion). Rhinitis (including hay fever) which is clinically active or history of moderate to severe rhinitis, or history of seasonal allergic rhinitis likely to be active at the time of inclusion into the study and/or requiring regular nasal corticosteroids on an at least weekly basis, within 30 days of admission to quarantine will be excluded. Participants with a history of currently inactive rhinitis (within the last 30 days) or mild rhinitis may be included at the PI's discretion. Participants with a physician diagnosed underactive thyroid who have been controlled on treatment for at least 6 months with evidence of a normal thyroid function test can be included at the discretion of the PI. Any concurrent serious illness including history of malignancy that may interfere with the aims of the study or a participant completing the study. Basal cell carcinoma within 5 years of initial diagnosis or with evidence of recurrence is also an exclusion. Participants with a history of psychiatric illness including depression and/or anxiety of any severity within the last 2 years can be included if the Patient Health Questionnaire (PHQ-9) and / or the Generalised Anxiety Disorder Questionnaire (GAD-7) is less than or equal to 4. Participants with a PHQ-9 or GAD-7 score of between 5 and 9 may be included following consultation with a Senior Physician (Clinical Lead for Screening) who may advise further consultation with the PI. Participants reporting physician diagnosed migraine can be included provided there are no associated neurological symptoms such as hemiplegia or visual loss. Cluster headache/migraine or prophylactic treatment for migraine is an exclusion. Participants with physician diagnosed mild irritable bowel syndrome not requiring regular treatment can be included at the discretion of the PI. 3. Participants who have smoked ≥10 pack years at any time (10 pack years is equivalent to one pack of 20 cigarettes a day for 10 years). 4. A total body weight ≤50 kg or body mass index (BMI) ≤18 kg/m2 or ≥35 kg/m2. 5. Females who: a) Are breastfeeding, or b) Have been pregnant within 6 months prior to the study. 6. History of anaphylaxis-and/or a history of severe allergic reaction or significant intolerance to any food or drug, as assessed by the PI. 7. Venous access deemed inadequate for the phlebotomy and cannulation demands of the study. Any significant abnormality altering the anatomy of the nose in a substantial way or nasopharynx that may interfere with the aims of the study and in particular any of the nasal assessments or viral challenge, (historical nasal polyps can be included, but large nasal polyps causing current and significant symptoms and/or requiring regular treatments in the last month will be excluded). Any clinically significant history of epistaxis (large nosebleeds) within the last 3 months of the first study visit and/or history of being hospitalised due to epistaxis on any previous occasion. Any nasal or sinus surgery within 3 months of the first study visit. PRIOR or CONCOMITANT MEDICATIONS AND ASSESSMENTS 9. Evidence of vaccinations within the 4 weeks prior to the planned date of viral challenge, unless medically necessary (e.g., during an outbreak or pandemic situation) and at the PI's discretion. Intention to receive any vaccination(s) before the day of Follow-up visit. (NB. No travel restrictions will apply after the Day 28 Follow-up visit). Receipt of influenza vaccine in the last 6 months prior to the planned date of viral challenge. 10. Receipt of blood or blood products, or loss (including blood donations) of 470 mL or more of blood during the 3 months prior to the planned date of viral challenge or planned during the 3 months after the final visit. 11. Receipt of any investigational drug within 3 months prior to the planned date of viral challenge. Receipt of three or more investigational drugs within the previous 12 months prior to the planned date of viral challenge. Prior inoculation with a virus from the same virus-family as the Challenge virus. Prior participation in another HVC study with a respiratory virus in the preceding 3 months, taken from the date of viral challenge in the previous study to the date of expected viral challenge in this study. Receipt of a pAb or biologic within the previous 12 months prior to the planned date of viral challenge. 12. a) Confirmed positive test for drugs of abuse and cotinine on first study visit. One repeat test allowed at PI discretion. b) History or presence of alcohol addiction, or excessive use of alcohol (weekly intake in excess of 28 units alcohol; 1 unit being a half glass of beer, a small glass of wine or a measure of spirits), or excessive consumption of xanthine containing substances (e.g., daily intake in excess of 5 cups of caffeinated drinks e.g., coffee, tea, cola). 13. A forced expiratory volume in 1 second (FEV1) <80%. 14. Positive HIV, active hepatitis A, B, or C test. 15. Those employed or immediate relatives of those employed at hVIVO or the Sponsor. 16. Any other finding that, in the opinion of the Investigator, deems the participant unsuitable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Exploratory randomised, Phase 2a, double blind, placebo-controlled study.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Normal Saline Placebo Control<br>Placebo control dosed 1 time via intravenous infusion | Other: Placebo<br>* Placebo Control<br>|
| Experimental: SAB-176 - 25mg/kg<br>Investigational Medicinal Product dosed 1 time at 25 mg/kg on day 1 via intravenous infusion | Biological: SAB-176<br>* Treatment of influenza<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate viral load by qRT-PCR of SAB-176 when compared to placebo | Area under the viral load-time curve (VL-AUC) of Influenza A/California/2009 H1N1 virus, as determined by qRT-PCR on nasal samples. | 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate peak viral load quantified by qRT-PCR. | Peak viral load as defined by the maximum viral load determined by quantifiable qRT-PCR measurements to evaluate the effect of SAB-176 in reducing viral loads in qRT-PCR due to Influenza A/California/2009 H1N1 virus compared to placebo. | 28 Days | 
| Evaluate duration of Influenza quantified by qRT-PCR. | Duration of Influenza quantifiable qRT-PCR measurements to evaluate the effect of SAB-176 in reducing the duration of Influenza in qRT-PCR due to Influenza A/California/2009 H1N1 virus compared to placebo. | 28 Days | 
| Evaluate peak viral load determined by cell culture. | Peak viral load as defined by the maximum viral load determined by quantifiable cell culture to evaluate the effect of SB-176 in reducing viral loads in cell culture due to Influenza A/California/2009 H1N1 virus, compared to placebo. | 28 Days | 
| Evaluate peak viral load area under the curve determined by cell culture. | VL-AUC of Influenza A/California/2009 H1N1 virus as determined by cell culture to evaluate the effect of SB-176 in reducing viral loads in cell culture due to Influenza A/California/2009 H1N1 virus, compared to placebo. | 28 Days | 
| Duration of influenza using peak viral load determined by cell culture. | Duration of influenza quantifiable by cell culture measurement to evaluate the effect of SB-176 in reducing viral loads in cell culture due to Influenza A/California/2009 H1N1 virus, compared to placebo. | 28 Days | 
| Area under the curve over time of total clinical symptoms score. | Area under the curve over time of total clinical symptoms score (TSS-AUC) as measured by graded symptom scoring system (categorical and visual analogue scales) to evaluate the effect of SAB-176 in reducing symptoms due to Influenza A/California/2009 H1N1 virus compared to placebo. | 28 Days | 
| Peak total clinical symptoms as measured by graded symptom scoring. | Peak symptom diary card score: peak total clinical symptoms (TSS) as measured by graded symptom scoring system (Categorical and visual analogue scales) to evaluate the effect of SAB-176 in reducing symptoms due to Influenza A/California/2009 H1N1 virus compared to placebo. | 28 Days | 
| Peak daily symptom score measured by the maximum daily sum of symptom score. | Peak daily symptom score: Individual maximum daily sum of symptom score to evaluate the effect of SAB-176 in reducing symptoms due to Influenza A/California/2009 H1N1 virus compared to placebo. | 28 Days | 
| Percent of participants with Grade 2 or higher symptoms. | Number (percent) of participants with Grade 2 or higher symptoms to evaluate the effect of SAB-176 in reducing symptoms due to Influenza A/California/2009 H1N1 virus compared to placebo. | 28 Days | 
| RT-PCR confirmed symptomatic influenza infection. | RT-PCR-confirmed symptomatic influenza infection defined as: RT-PCR-Confirmed influenza infection and Clinical symptoms to evaluate the effect of SAB-176 in reducing the incidence of symptomatic infection due to Influenza A/California/2009 H1N1 virus compared to placebo. | 28 Days | 
| Culture lab-confirmed reduction of symptomatic influenza infection. | Culture lab-confirmed reduction of symptomatic influenza infection defined as: lab-confirmed culturable influenza infection and clinical symptoms to evaluate the effect of SAB-176 in reducing the incidence of symptomatic infection due to Influenza A/California/2009 H1N1 virus compared to placebo. | 28 Days | 
| Occurrence of unsolicited adverse events (AEs) from IV infusion up to Day 28 follow-up. | Occurrence of unsolicited adverse events (AEs) from IV infusion up to Day 28 follow-up to evaluate the safety of SAB-176 when compared to placebo. | 28 Days | 
| Occurrence of serious adverse events (SAEs) from IV infusion up to Day 28 follow up. | Occurrence of serious adverse events (SAEs) from IV infusion up to Day 28 follow up to evaluate the safety of SAB-176 when compared to placebo. | 28 Days |