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Stopping Strep Throat With Antibodies in Healthy Adults.

ConditionStreptococcal Pharyngitis
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-40
SponsorMurdoch Childrens Research Institute

About this trial

This research group has previously established a safe and reliable model of experimental human streptococcal pharyngitis (a 'strep throat' human challenge model). The CHIVAS-IgG study will use this model to understand the ways in which antibodies help protect humans against strep throat infections.

Carefully screened healthy adults who are at very low risk of complicated strep disease will be admitted to a clinical trials unit where they will be randomly allocated to receive a licensed commercial 'intravenous immunoglobulin' product that is a mixture of antibodies from thousands of humans, or a placebo ('saline' or salty water), by intravenous injection.

About a week after the injection of antibodies or saline, they will have strep throat bacteria (Streptococcus pyogenes) 'painted' with a swab on the back of their throat, as this research group has done previously for over 100 healthy adults. The participants will be observed closely for about 5 days to see if they develop symptoms (sore throat) and signs (red throat, big tonsils, sore glands) of strep throat. During that time, multiple throat and nasal swabs will be collected along with saliva samples, blood tests, and photos. Before discharge from the clinical trials unit, every participant will be treated with antibiotics to make sure any strep bacteria is removed.

Participants will return for study visits at about 1 week and 1 month later, to check on how they are feeling and to collect more samples to understand how their immune system responds to the strep challenge.

This study is an important step on the way to developing a vaccine to prevent strep throat, strep skin infections, and dangerous Streptococcus pyogenes diseases like invasive infections and post-infectious problems like rheumatic heart disease.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Males or females, aged 18 - 40 years (inclusive) on the day of informed consent.

Medically healthy, which can be determined by medical history, physical examination, BMI, transthoracic echocardiogram, non-clinically significant laboratory profiles, vital signs, and 12-lead ECG at screening, as deemed necessary by the research physician or investigator.

Normal systolic (SBP) and diastolic blood pressure (DBP), i.e. SBP 90 - 140 mmHg and DBP of 60 - 90 mmHg or as determined by the research physician or investigator. Vital signs can be repeated up to two times.

Normal resting heart rate (HR), i.e. 50-100 bpm or as determined by the research physician or investigator (confirmed by one repeat at screening).

Disqualifiers

History of anaphylactic or severe systemic reaction to human immune globulin

Known serum IgA deficiency

Received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation within 3 months of informed consent.

Donated blood or plasma within 1 month of informed consent.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Streptococcus pyogenes M1 challenge strain

    Biological/Vaccine

    All participants will be inoculated by direct oropharyngeal swab application from vials containing 1-5 x 10\^5 CFU bacteria in 1 mL animal-free liquid media.

  • Intravenous immunoglobulin (IVIG)

    Biological/Vaccine

    Participants will be randomised 1:1 to receive IVIg or placebo (0.9% sodium chloride) prior to pharyngeal challenge with Streptococcus pyogenes.

  • Saline (NaCl 0,9 %) (placebo)

    Drug

    Participants will be randomised 1:1 to receive IVIg or placebo (0.9% sodium chloride) prior to pharyngeal challenge with Streptococcus pyogenes.

Treatment groups

60 Participants
are divided into 2 treatment groups
Group A: Passive immunisation (intravenous immunoglobulin)Experimental treatment 2 interventions
Group B: Passive immunisation (saline placebo)Placebo comparator 2 interventions

Trial outcomes

Primary outcomes

1

Acute symptomatic pharyngitis (disease) - proportion of participants in each arm who reach the study pharyngitis endpoint

Proportion of participants in each arm who develop pharyngitis according to pre-defined clinical and microbiological diagnostic criteria, comprising sore throat, physical examination signs of pharyngitis and tonsillitis, and microbiological confirmation of S. pyogenes by culture and nucleic acid amplification test of throat swabs

Time frame
Up to 5 days after the challenge dose of M1 S. pyogenes is administered.

Secondary outcomes

1

Changes in Streptococcus pyogenes pharyngeal colonisation (infection) - proportion of participants in each arm with established colonisation as measured by throat swab culture and strain-specific qPCR

To evaluate effects of IVIg on pharyngeal colonisation by M1 S. pyogenes after challenge: Bacterial colonisation measured by culture and strain-specific qPCR of throat swabs (including participants without symptoms). Proportion of participants in each arm with established colonisation (at 2 or more timepoints at least 12 hours apart). Comparison of overall colonisation density between participants in each arm (i.e. area under the curve of sequential qPCR results).

Time frame
Up to 40 days after the challenge dose of M1 S. pyogenes is administered.
2

Changes in early inflammatory response between participants in each arm - as measured by high-dimensional flow cytometry and multiplex cytokine and chemokine assays

To evaluate effects of IVIg on the early inflammatory response changes to M1 S. pyogenes challenge. Comparison of baseline and subsequent peripheral blood leukocyte, cytokine and chemokine levels between participants in each arm.

Time frame
Up to 16 days after the challenge dose of M1 S. pyogenes is administered
3

Changes in serum opsonophagocytic activity between participants in each arm

To characterise changes in serum opsonophagocytic activity against the M1 challenge strain (Opsonic Index; OI) from baseline (pre-IVIg or placebo) to the pre-challenge timepoint (Day 0).

Time frame
Prior to passive immunisation (IVIg or placebo) and prior to challenge (Day 0).
4

Changes in serum antigen-specific binding antibody responses between participants in each arm

Changes in serum IgG levels to: type-specific M1 peptide and other S. pyogenes antigens, including candidate vaccine antigens.

Time frame
Baseline (Screening) through to study completion, an average of 3 months for each participant.

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Murdoch Childrens Research Institute

Lead sponsor

University of Melbourne

Collaborator

University of Sheffield

Collaborator

Medical Research Council Unit, The Gambia

Collaborator

Walter and Eliza Hall Institute of Medical Research

Collaborator

London School of Hygiene and Tropical Medicine

Collaborator

Source ClinicalTrials.gov

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