| 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 | 18.0 |
| 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 with PrEP-001 in asthmatic subjects subsequently challenged with HRV-16 on the changes in clinical symptoms when compared to placebo |
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| E.2.2 | Secondary objectives of the trial |
Efficacy:
To determine the prophylactic effect of PrEP-001 after repeated intranasal dosing in asthmatic subjects subsequently challenged with HRV-16 on clinical signs and symptoms of HRV infection, rates of clinical illness, and viral shedding.
Safety:
To determine the safety and tolerability of PrEP-001 after repeated intranasal dosing in asthmatic 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).
Physician diagnosed asthma for at least 6 months prior to Screening and using treatment equivalent up to and including Global Initiative for Asthma (GINA) Stage 3.
A pre-bronchodilator FEV1 ≥ 60% of predicted subject’s normal value at the first screening, on admission to quarantine, and prior to dosing on Day -2.
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 in a heterosexual relationship (i.e., the criteria do not apply to those in a same sex relationship):
- 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).
Female study subjects who are not heterosexually active must have periodic confirmation of continued abstinence from heterosexual intercourse
Or
- 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, acceptable forms of contraception include:
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 at entry to quarantine, and continuing until 90 days after the date of Viral Challenge.
ii. Male subjects must not donate sperm following discharge from quarantine until 90 days after the date of Viral Challenge
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 from14 days prior to entry to quarantine and continuing until 90 days after the date of Viral Challenge.
An informed consent document signed and dated by the subject and the Investigator.
Sero-suitable for the Challenge Virus.
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| E.4 | Principal exclusion criteria |
Any ex-smoker or smoker with a history of more than 10 pack-years.
History of life-threatening asthma, Diagnosis of COPD as defined by the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2014 guidelines.
Females who: • Are breastfeeding, or • Have been pregnant 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 medical and psychiatric conditions (as defined in section 5.4 of the study protocol).
History or evidence of autoimmune disease or known immunodeficiency of any cause – with the exception of atopic eczema/atopic dermatitis as described in exclusion criteria number 5 of the protocol.
Exacerbation of asthma symptoms within 1 month prior to Screening and Day -4 and requiring the use of oral steroids, antibiotics, Accident and Emergency visit, or hospital admission.
Positive HIV, active hepatitis A virus (HAV), Hepatitis B virus (HBV), or Hepatitis C virus (HCV) test.
Any significant abnormality altering the anatomy of the nose or nasopharynx (including significant nasal polyps).
Any clinically significant history of epistaxis (nosebleeds) within the last 12 months AND/OR • History of being hospitalized due to epistaxis on any previous occasion.
Any nasal or sinus surgery within 6 months of Viral Challenge.
Recurrent history of fainting.
Twelve-lead ECG recording with clinically relevant signs of pathology and conduction disturbances as judged by the Investigator.
Confirmed positive test for drugs of abuse and/or cotinine deemed by the Investigator to be clinically significant.
Venous access deemed inadequate for the phlebotomy and cannulation demands of the study.
Evidence of vaccinations within the 4 weeks prior to the planned date of first dosing with IMP. • Intention to receive any vaccination(s) before the last day of Follow-up. (NB. No vaccine restrictions will apply after the Day 28 Follow-up visit).
Those employed or immediate relatives of those employed at hVIVO.
Receipt of blood or blood products, or loss (including blood donations) of 450 mL or more of blood during the 1 month 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 first dosing with IMP on Day -2 of any medication or product (prescription or over-the-counter [OTC]), 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. • Receipt of 3 or more investigational drugs within the previous 12 months prior to the planned date of first dosing with IMP. • Prior inoculation with the same virus as the Challenge Virus. • Participation in another clinical study with an IMP at the same time as the present study. • Prior participation in another HVC study with a respiratory virus in the preceding 12 months, taken from the date of Viral Challenge in the previous study to the date of admission to quarantine in this study.
Receipt of systemic (intravenous and/or oral) glucocorticoids or systemic antiviral drugs within 3 months prior to the planned date of first dosing with IMP .
Use or anticipated use during the conduct of the study of concomitant medications ( as defined in the study protocol).
Use of any prohibited medications as detailed in Section 8.1 of the study protocol.
History suggestive of respiratory infection within 6 weeks prior to admission to the Quarantine Unit. • Presence of significant respiratory symptoms on the day of first dosing with IMP.
History or presence of drug addiction, or excessive use of alcohol (weekly intake in excess of 28 units alcohol; one unit being a glass of beer, wine or a measure of spirits), or excessive consumption of xanthine containing substances (e.g., daily intake in excess of 5 cups of coffee, tea, cola).
Presence of fever, defined as subject presenting with a temperature reading of ≥ 37.9 oC on Day -4 and/or pre-Challenge on Day 0.
History of anaphylaxis-and/or a history of severe allergic reaction or significant intolerance to any food or drug as assessed by the PI. • Known allergies to: - excipients in the Challenge Virus inoculum -the IMP as stipulated in the protocol - antibiotics in 2 or more classes of antibiotics (i.e., beta lactams, cephalosporins, fluoroquinolones or glycopeptides [e.g., vancomycin]).
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) |
| AUC of total symptom score post Viral Challenge |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Up to Day 28 (+/- 5 Days) |
|
| E.5.2 | Secondary end point(s) |
Efficacy endpoints:
Symptom scores
-AUC of symptom score (URT, LRT and SRT) post Viral Challenge
-duration of symptoms
-peak symptom score
- time to peak symptom
- time to resolution from peak symptoms
Incidence(s) of illness and infection:
-viral shedding
-incidence of laboratory-confirmed HRV illness based on the incidence of HRV-like-illness and laboratory-confirmed infection
-laboratory confirmed HRV-16 infection
-HRV-like-illness
-sub-clinical infection
-upper respiratory tract illness
-lower respiratory tract illness
-febrile illness
-systemic illness
-non-sick and uninfected
-viral replication
-seroconversion (as calculated by a ratio of HRV-16 antibodies at follow-up versus pre-dose).
Viral load parameters (using TCID50 and/or RT-PCR)
- area under the curve (AUC) of viral load
-duration of virus shedding
-peak virus shedding
-time to peak viral shedding
-time to resolution from peak viral shedding.
Total weight of mucus produced.
Change in lung function (including PEF) compared with pre-Challenge.
Safety:
Incidence of treatment-emergent adverse events (AEs), severity, seriousness and causality.
Absolute values and change from baseline in routine clinical laboratory parameters by timepoint.
Absolute values and change from baseline in vital signs parameters by timepoint.
Physical examination findings.
Absolute values and change from baseline in spirometry parameters by timepoint (analysed descriptively).
12-lead electrocardiogram (ECG).
Concomitant medications.
Number of asthma exacerbations post Viral Challenge. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Up to Day 28 (+/- 5 Days) |
|
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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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