| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Human Rhinovirus (HRV-16) |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10075163 |
| E.1.2 | Term | Human rhinovirus test |
| E.1.2 | System Organ Class | 10022891 - Investigations |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess the prophylactic effect of repeated intranasal dosing of PrEP-001 in healthy subjects, subsequently challenged with HRV-16, on the changes in clinical symptoms when compared to placebo at two different dosing regimens |
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| E.2.2 | Secondary objectives of the trial |
To determine the prophylactic effect of PrEP-001 after repeated nasal dosing in healthy subjects subsequently challenged with HRV-16, on clinical signs and symptoms and rates of clinical illness
To determine the safety and tolerability of PrEP-001 after repeated nasal dosing in healthy subjects subsequently challenged with HRV-16 |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Aged 18 to 55 years on the day of first dosing with Investigational Medicinal Product (IMP)
In good health with no history of major medical conditions from the medical history, physical examination, and routine laboratory tests as determined by the Investigator at a screening evaluation. A subject with a history of Herpes type 1 or 2 infection may be included if there are no active lesions present and the subject is not taking active medication.
A total body weight ≥50 kg and Body Mass Index (BMI) ≥18 kg/m2. If the BMI is more than 30 kg/m2, the subject may be included if the waist measurement is less than 102 cm (male), or less than 88 cm (female).
The following inclusion criteria are applicable to subjects who are in a heterosexual relationship and female subjects in a female same sex relationship (i.e. the criteria do not apply to those in a male same sex relationship):
a) True abstinence - when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception).
Or
b) Two forms of effective contraceptive methods among (between) the couple, which are defined as:
• For males:
i. Condom with spermicidal foam/gel/film/cream, sterilisation (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate. This applies only to males participating in the study).
• For females:
i. Women no longer of child bearing potential (post-menopausal females are defined as having a history of amenorrhea for at least 2 years, otherwise they should have documented status as being surgically sterile or post hysterectomy. The latter applies only to female subjects participating in the study).
ii. If of childbearing potential, then acceptable forms of contraception include:
o Established (a minimum of 2 weeks prior to first dosing with IMP) use of oral, injected or implanted hormonal methods of contraception.
- Placement of an intrauterine device (IUD) or intrauterine system (IUS).
- Barrier methods of contraception or occlusive cap (diaphragm or cervical/vault caps), both with one of the following - spermicidal foam/gel/film/cream/suppository.
• The longevity of contraception is as follows:
i. Male subjects must comply with agreed contraception from the first IMP dosing, and continuing until 90 days after the date of the last IMP dosing or Viral Challenge which ever happens later.
ii. Male subjects must not donate sperm following the first IMP dosing, and continuing until 90 days after the date of the last IMP dosing or Viral Challenge which ever happens later.
iii. Female subjects of childbearing potential must have a negative pregnancy test at screening and just prior to the date of first dosing with IMP and must be using contraception consisting of two forms of birth control (one of which must be a barrier method) starting from at least 14 days prior to the first IMP dosing and continuing until 90 days after the date of the last IMP dosing or Viral Challenge whichever happens later.
An informed consent document signed and dated by the subject and the Investigator.
Sero-suitable for the Challenge Virus.
Subjects must be willing to comply with the protocol visit schedule including both face to face and phone visits.
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| E.4 | Principal exclusion criteria |
Subjects who have a significant history of any tobacco use at any time
Females who are breastfeeding or pregnancy within 6 months prior to the study, or have a positive pregnancy test at any point during screening or prior to first dosing with IMP
Any history or evidence of any clinically significant cardiovascular, dermatological gastrointestinal, endocrine, haematological, hepatic, immunological, metabolic, urological, neurological, renal, and/or other major disease that, in the opinion of the Investigator, may interfere with a subject completing the study is exclusionary
•Subjects with clinically mild atopic eczema/atopic dermatitis may be included at the Investigator's discretion
Subjects with a diagnosis of mild or moderate depressive episode(s) which occurred 2 or more years ago, with good evidence of preceding stressors and which resolved within approximately 3 months may be included in the Investigator's opinion
During screening, if subjects have a total cholesterol level > 6mmol/l they will be excluded from the study.
Any concurrent serious illness may interfere with a subject completing the study
Abnormal pulmonary function in opinion of Investigator as evidenced by the responses to the respiratory screening questions and/or clinically significant abnormalities in spirometry
A history or evidence of an autoimmune disease or known immunodeficiency
Subjects with any history of COPD, pulmonary hypertension, asthma or chronic lung condition of any aetiology
History childhood asthma before the age of 12 years is acceptable provided subject is asymptomatic without treatment. Subjects with single episode of wheezing (lasting less than 8 weeks) after age 12 can be included at Investigator's discretion provided episode was more than 4 yrs ago not requiring hospital admission and/or oral/intravenous steroids
Positive HIV, active hepatitis A, B or C test
Significant abnormality altering anatomy of nose/nasopharynx
Clinically significant history of epistaxis within last 12 months
Nasal/sinus surgery within 6 months of first dosing
Recurrent history of fainting
Twelve-lead ECG recording with clinically relevant signs of pathology and conduction disturbances as judged by Investigator
Confirmed positive test for drugs of abuse deemed by Investigator as clinically significant
Venous access deemed inadequate for phlebotomy and cannulation demands of study
Clinically significant allergies such as allergy to the excipients in the Challenge Virus inoculum stipulated in protocol
Evidence of vaccinations within 4 weeks prior to planned date of first dosing with IMP or intention to receive any vaccination(s) before last day of study
Those employed, or immediate relatives of those employed, at hVIVO or Sponsor
Receipt of blood or blood products, or loss of 450 mL or more of blood during 3 months prior to the planned date of first dosing with IMP or planned during the 3 months after the final visit
Use within 7 days prior to the planned date of first dosing with IMP of any medication or product, for symptoms of hay fever, rhinitis, nasal congestion or respiratory tract infections including the use of nasal steroids
Receipt of any investigational drug within 3 months prior to the planned date of first dosing with IMP or receipt of three or more investigational drugs within the previous 12 months prior to the planned date of first dosing with IMP
Prior inoculation with a virus from the same virus-family as the Challenge Virus or prior participation in another Human Viral Challenge study with a respiratory virus in the preceding 12 months taken from the date of first dosing with IMP in the previous study to the date of expected first dosing in this study
Receipt of systemic glucocorticoids or systemic antiviral drugs within 6 months prior to the planned date of first dosing with IMP
History of chemotherapy of therapy with immunomodulators
History suggestive of respiratory infection within 14 days prior to first dosing or presence of significant respiratory symptoms on the day of first dosing with IMP
Use or anticipated use during the conduct of the study of concomitant medications, including vitamins or herbal and dietary supplements within the specified windows, unless in the opinion of the Investigator and/or Sponsor’s Medical Expert, the medication will not interfere with the study procedures or compromise subject safety. Specifically, the following are excluded:
•Herbal supplements within 7 days prior to the planned date of first dosing with IMP
•Chronically used medications, vitamins or dietary supplements, including any medication known to be an inducer or inhibitor of cytochrome P450 enzymes, within 21 days prior to the planned date of dosing with IMP
•Over the counter medications where the dose taken over the preceding 7 days prior to the planned date of first dosing with IMP
Any other finding that, in the opinion of the Investigator, deems the subject unsuitable for the study
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Overall total symptom score, defined as the sum of the total symptom scores from day 1 to day 8, inclusive, using the 10-point symptom diary card. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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| E.5.2 | Secondary end point(s) |
• The area under the curve (AUC) of symptom scores , using symptoms from day 1 to day 8 from the 10-point symptom diary card, calculated separately for total symptoms, upper respiratory tract, lower respiratory tract and systemic viral symptoms
• Overall symptom score, defined as the sum of the symptom scores from day 1 to day 8, inclusive, using the 10-point symptom diary card, calculated separately for upper respiratory tract, lower respiratory tract and systemic viral symptoms
• Duration of symptoms
• Peak symptom score
• Time to peak symptom
• Time to resolution from peak symptoms
Incidence(s) of illness and infection:
• Laboratory confirmed HRV-16 infection (as defined by a positive result in a quantitative polymerase chain reaction (qPCR) assay from the combined nasal washes of days 3, 4 and 5)
• HRV-like illness
• Sub-clinical infection
• Upper respiratory tract illness
• Lower respiratory tract illness
• Febrile illness
• Systemic illness
• Asymptomatic and uninfected
Secondary safety endpoints:
• AEs/SAEs
• Vital signs
• Biochemistry/haematology and coagulation
• ECGs
• Spirometry
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Up to Day 10 (+/- 2 Days) |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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