| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Respiratory Syncytial Virus Infection |
|
| E.1.1.1 | Medical condition in easily understood language |
| RSV is a common virus that can cause severe chest infections in small children, adults with heart, lung and immune system conditions and elderly people. |
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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 | 20.0 |
| E.1.2 | Level | SOC |
| E.1.2 | Classification code | 10021881 |
| E.1.2 | Term | Infections and infestations |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 evaluate the antiviral activity of EDP-938 compared to placebo in healthy adult subjects inoculated with RSV-A Memphis 37b |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate EDP-938 compared to placebo in healthy adult subjects inoculated with RSV-A Memphis 37b in terms of:
o Clinical symptoms
o Viral load
o Safety and Tolerability
• To characterise the PK profile of multiple doses of EDP-938 and metabolites in healthy adult subjects inoculated with RSV-A Memphis 37b.
• To Characterise the relationship between Plasma PK of EDP-938 and viral load AUC (RT-PCR) and total symptom score AUC
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Aged 18 to 55 years from the day prior to signing the consent form.
2. In good health with no history of major medical conditions that will interfere with subject safety, as defined by medical history, physical examination, and routine laboratory tests and determined by the Investigator at screening evaluation.
3. Subjects will have a documented medical history either prior to entering the study and/or following medical history review with the study physician at screening.
4. A total body weight ≥ 50 kg and Body Mass Index (BMI) ≥ 18 kg/m2 and ≤ 30kg/m2.
5. • Female subjects must have a negative pregnancy test at screening and prior to viral challenge.
• Female subjects of childbearing potential must use one form of highly effective contraception. Hormonal methods must be in place from at least 2 weeks prior to quarantine. The contraception use must continue until 90 days after the date of Viral Challenge/last dosing with IMP (whichever occurs last). Highly effective contraception as below:
Established (a minimum of 2 weeks prior to admission) use of hormonal methods of contraception below.
Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
Oral, Intravaginal, Transdermal.
Progestogen-only hormonal contraception associated with inhibition of ovulation:
Oral, injectable, implantable 2
Note: when hormonal methods of contraception are used, male partners are required to use a condom with a spermicide.
Intrauterine device (IUD) , Intrauterine hormone-releasing system (IUS) , Bilateral tubal ligation, Male sterilisation (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.
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.
•Female subjects who are no longer of child bearing potential.
Post-menopausal females as defined in the protocol as having a history of amenorrhea for at least 2 years, otherwise they should have documented status as being surgically sterile or post hysterectomy.
•Male subjects must agree to the contraceptive requirements below at entry to quarantine and continuing until 90 days after the date of Viral challenge / last dosing with IMP (whichever occurs last).
Use a condom with a spermicide to prevent pregnancy.
Male sterilisation with the appropriate post vasectomy documentation. This applies only to males participating in the study.
In addition, for female partners of child bearing potential, that partner must use another form of contraception such as one of the highly effective methods mentioned above for female subjects.
True abstinence as defined in the protocol.
In addition to the contraceptive requirements above, male subjects must agree not to donate sperm following discharge from quarantine until 90 days after the date of Viral Challenge/last dosing with IMP (whichever occurs last).
6. An informed consent document signed and dated by the subject and the Investigator.
7. Sero-suitable to the challenge virus.
• The serology result obtained suggests that the subject is sensitive to RSV infection, i.e. they are likely to be infected following inoculation with the challenge virus.
8. Subjects who have experienced no more than one mild episode of wheeze (mild is defined as having been treated with bronchodilators only) after the age of 12, may be included at the Investigator’s discretion, providing the episode lasted no more than 2 weeks, and ended more than 1 year ago. A history of childhood asthma up to and including the age of 12 years is acceptable. |
|
| E.4 | Principal exclusion criteria |
1. Subjects 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]).
• Of those subjects that have smoked <10 pack years at any time, a subject will be excluded if, in the last month (i.e. 30 days) prior to admission, they have used tobacco in any form (e.g. smoking or chewing) or other nicotine-containing products in any form (e.g. gum, patch and electronic cigarettes).
2. Females who:
a) Are breastfeeding, or
b) Have been pregnant within 6 months prior to the study, or
c) Have a positive pregnancy test at any point during screening or prior to Viral Challenge/first dosing with IMP (whichever occurs first).
3. • Any history or evidence of any clinically significant or currently active cardiovascular, respiratory, dermatological, gastrointestinal, endocrinological, haematological, hepatic, immunological (including immunesuppression), metabolic, urological, renal, neurological, or psychiatric disease (including subjects with a history of depression and/or anxiety with associated severe psychiatric comorbidities, for example psychosis; subjects with a history of depression of any severity within the last 2 years should only be included if the PHQ-9 score is less than or equal to 4)
• And/or other major disease that, in the opinion of the Investigator, may interfere with a subject completing the study and necessary investigations.
• The following conditions apply:
• Subjects 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).
• Subjects 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 (TFT) can be included at the discretion of the PI.
• 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. Subjects with a history of currently inactive rhinitis (within the last 30 days) or mild rhinitis may be included at the PI’s discretion.
• Any concurrent serious illness including history of malignancy that may interfere with the aims of the study or a subject completing the study. Basal cell carcinoma within 5 years of initial diagnosis or with evidence of recurrence is also an exclusion.
• Subjects reporting physician diagnosed migraine can be included as long as there are not associated neurological symptoms such as hemiplegia or visual loss. Cluster headache/migraine or prophylactic treatment for migraine is an exclusion.
4. A forced expiratory volume in 1 second (FEV1) < 80%.
5. Subjects with any history of physician diagnosed and/or objective test confirmed asthma, COPD, pulmonary hypertension, or chronic lung condition of any aetiology.
6. Positive human immunodeficiency virus (HIV), active hepatitis A (HAV), B (HBV), or C (HCV) test.
7. 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).
8. Any clinically significant history of epistaxis (large nosebleeds) within the last 3 months and/or history of being hospitalized due to epistaxis on any previous occasion.
9. Any nasal or sinus surgery within 3 months of Viral Challenge.
10. Twelve-lead ECG recording with clinically relevant abnormalities as judged by the study physician/PI.
11. Confirmed positive test for drugs of abuse on admission.
12. Venous access deemed inadequate for the phlebotomy and cannulation demands of the study.
13. Presence of fever, defined as subject presenting with a temperature reading of ≥ 37.9 °C on Day -2, Day -1, and/or pre-Challenge on Day 0.
14. a) Evidence of vaccinations within the 4 weeks prior to the planned date of Viral Challenge/first dosing with IMP (whichever occurs first).
b) Intention to receive any vaccination(s) before the last day of Follow-up. (NB. No travel restrictions will apply after the Day 28 Follow-up Visit).
15. Those employed or immediate relatives of those employed at hVIVO or the Sponsor.
[Please refer to clinical protocol for a full list of exclusion criteria] |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The area under the curve (AUC) for RSV viral load measured in nasal washes by quantitative reverse transcription polymerase chain reaction (RT-qPCR), in subjects inoculated with RSV-A Memphis 37b. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Secondary endpoints relating to efficacy:
o Effect of EDP-938 compared to placebo on RSV symptoms using the 10- item diary card completed by the subjects.
o Total weight of nasal mucus produced via weighed paper tissues.
o Additional viral load endpoints calculated separately using data from RT-qPCR of nasal wash comparing placebo and EDP-938 treated.
Secondary endpoints relating to safety:
• Adverse Events (AEs)
• Physical Examination
• Vital signs
• 12-lead Electrocardiograms (ECGs)
• Spirometry
• Clinical laboratory results (including biochemistry, haematology, coagulation (if required), cardiac enzymes and urine analysis)
Secondary endpoints related to PK parameters:
·Plasma PK parameters of EDP938 (and metabolites) following repeat dose administration in healthy adult subjects inoculated with RSV-A Memphis 37b
· Plasma PK (AUC) correlations with viral load AUC and Total Symptom Score AUC
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| 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
|
| Last subject of the last scheduled visit. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | 15 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 15 |
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