| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| Respiratory infection with respiratory syncytial virus (RSV) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10038717 |
| E.1.2 | Term | Respiratory syncytial viral infections |
| E.1.2 | System Organ Class | 100000004862 |
|
| 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 |
The primary efficacy objective and endpoint of the study is to evaluate the antiviral effect (as defined by reduction in AUC of viral load) of aerosolized MDT-637, in a manner which mimics the timing of the infection and potential treatment application in infants and children.
|
|
| E.2.2 | Secondary objectives of the trial |
The secondary efficacy objectives include:
- Virology
o Antiviral effect (as defined by reduction in log AUC viral load by TCID50)
o Duration and peak of virus shedding
- Clinical
o The reduction in nasal mucous production
o The reduction in symptom scores
- Device
o Performance of the EPIC Inhaler
The safety objectives are:
- To evaluate the safety profile of MDT-637 in the RSV-A (Memphis 37b) infected human respiratory tract.
- To determine the safety of the inhaler device
The exploratory objectives are:
- To investigate the potential for the development of viral resistance.
- To determine the quality of sleep |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Age 18 to 45 years, inclusive.
2. In good health with no history of major medical conditions from medical history, physical examination, and routine laboratory tests as determined by the Investigator by a screening evaluation.
3. A Total body weight ≥50kg and a BMI >18. If the BMI is above 28 the subject may be included if the waist measurement is less than 94 cm (male), or less than 80 cm (female).
4. (a) Male subjects must use highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting at entry to Quarantine and continue until the Day 28 follow-up visit.
(b) In addition, male subjects must not donate sperm following discharge from Quarantine until the Day 28 follow-up visit.
(c) Female subjects must be either:
- post-menopausal (defined as at least one year documented history without any menses/or post-menopausal females (confirmed by FSH test) prior to Screening or
- documented status as surgically sterile or post hysterectomy or
- if of childbearing potential, must have a negative urine pregnancy test at SSS and must be using highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting at entry to Quarantine and continue until the Day 28 follow-up visit.
Acceptable forms of effective contraception include:
- Established use of oral, injected or implanted hormonal methods of contraception
- Placement of an intrauterine device (IUD) or intrauterine system (IUS).
- Barrier methods of contraception: Condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
- Male sterilisation (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). [For female subjects on the study, the vasectomised male partner should be the sole partner for that subject].
5. An informed consent document voluntarily signed and dated by the subject and investigator
6. Sero-suitable for Challenge Virus |
|
| E.4 | Principal exclusion criteria |
1. Subjects who have a significant history of any tobacco use at any time (≥ total 10 pack year history)
2. Subjects who are pregnant or breast feeding; or who are male and have a female partner who is pregnant, nursing, or is planning to become pregnant during the study period
3. Any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinological, haematological, hepatic, immunological, metabolic, urological, neurological, psychiatric, renal, and/or other major disease or malignancy, as judged by the medical investigator.
Eczema/Atopic Dermatitis: subjects with clinically mild eczema/atopic dermatitis may be included at the Investigator's discretion.
Psoriasis: patients with active psoriasis affecting less than 5% of the body's surface area for the past five years can be included at the Investigator's discretion. Patients with a history of completely resolved guttate psoriasis can be included.
Subjects with a diagnosis of a single mild or moderate depressive episode two or more years ago, with good evidence of preceding stressors and which resolved within approximately three months, may be included at the Investigator's discretion.
4. Abnormal pulmonary function in the opinion of the Investigator as evidenced by clinically significant abnormalities in spirometry.
5. History or evidence of autoimmune disease or known immunodeficiency of any cause.
6. Subjects with any history of asthma, COPD, pulmonary hypertension, reactive airway disease, or any chronic lung condition of any aetiology.
7. A history of childhood asthma before the age of 12 is acceptable provided the subject is asymptomatic without treatment. Patients with a single episode of wheezing after age 12 (lasting less than eight weeks) can be included at the Investigator's discretion provided the episode is more than four years ago and did not require a hospital admission and/or oral steroids.
8. Positive HIV, hepatitis B , or hepatitis C test.
9. Any significant abnormality altering the anatomy of the nose or nasopharynx.
10. Any clinically significant history of epistaxis.
11. Any nasal or sinus surgery within 6 months of inoculation.
12. Recurrent history of clinically significant autonomic dysfunction.
13. Any laboratory test or ECG, which is abnormal and deemed by the investigator(s) to be clinically significant.
14. Confirmed positive test for cotinine and /or drugs of abuse deemed by the Investigator to be clinically significant.
15. Unable to comply with study procedures including venous access deemed inadequate for the phlebotomy and cannulation demands of the study.
16. Any known allergies to the excipients in the Challenge Virus inoculum or investigational product. Specifically severe lactose intolerance.
17. Health care workers who work in units with severely immuno-compromised patients.
18. Presence of household member or close contact (for an additional two weeks after discharge from the isolation facility) who:
has known immunodeficiency
is receiving immunosuppressant medication
is undergoing or soon to undergo cancer chemotherapy within 28 days of viral inoculation
has been diagnosed with emphysema, COPD, or other severe lung disease and resides in a nursing home.
has received a bone marrow or solid organ transplant
19. Evidence of vaccinations within the four weeks prior to Human Viral Challenge. Intention to receive travel vaccination(s) before the Day 28 Follow Up Visit.
20. Those employed or immediate relatives of those employed at RVL or the Sponsor.
21. Receipt of blood or blood products, or loss (including blood donations) of 450 mL or more of blood, during the 3 months prior to inoculations.
22. Use within 28 days prior to Human Viral Challenge (Day 0) of nasal steroids. Use of any prescription medication within 14 days of Day -2 or over-the-counter preparations, within 5 days of Day -2 for symptoms of hay fever, rhinitis, nasal congestion or respiratory tract infection deemed by the Investigator to be clinically significant.
23. For investigational products, receipt of small molecule product within 3 months or a biological product within 12 months prior to inoculation. Prior participation in a clinical trial with the same strain of respiratory virus. Participation in any other Human Viral Challenge Study with a respiratory virus within one year prior to the day of inoculation/first dosing with IMP.
24. Receipt of systemic: glucocorticoids, antiviral drugs, or Igs or any other cytotoxic or immunosuppressive drug within 6 months prior to dosing. Receipt of any systemic chemotherapy agent at any time.
25. Presence of significant respiratory symptoms existing on the day of challenge or between admission to the unit and inoculation with virus. History suggestive of respiratory infection within 14 days prior to admission to the unit.
26. Any other finding that, in the opinion of the Investigator or Sponsor, deems the subject unsuitable for the study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint of the study is to evaluate the antiviral effect (as defined by reduction in AUC of viral load) of aerosolized MDT-637, in a manner which mimics the timing of the infection and potential treatment application in infants and children.
This will be measured by analysing the area under the curve (AUC) for each subject via Quantitative Polymerase Chain Reaction Viral Load. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Frequency and method:
The Viral load will be detected and quantified in using aliquots from the nasal wash samples taken twice a day from Quarantine Day 1 post inoculum through to Day 12. The samples will be processed by Retroscreen Laboratories and shipped to Sponsor designated
laboratory in two separate batches per quarantine for analysis. |
|
| E.5.2 | Secondary end point(s) |
The secondary efficacy objectives include:
- Virology
o Antiviral effect (as defined by reduction in log AUC viral load by TCID50)
o Duration and peak of virus shedding
- Clinical
o The reduction in nasal mucous production
o The reduction in symptom scores
- Device
o Performance of the EPIC Inhaler
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Virology:
The Time point of evaluation of this end points will be evaluated by Nasal wash for Virology and Virus shedding twice daily on Day 1 to day 12 Post-Inoculation. The time point for evaluation using viral serology is Day -2 and Day 28.
Clinical:
The Time point of evaluation of Nasal mucous production is Once daily on Day 1 to Day 12 post-Inoculation.
The Time point of Symptom scores is Four times daily on Day 1 to Day 12 Post-Inoculation. |
|
| 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 | Yes |
| 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 | 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
|
| The End of Trial is defined as the last scheduled visit for the last subject (LSLV). If a safety visit is required after the last scheduled visit, this will be scheduled based upon the CI’s discretion as a duty of care and in line with ICH-E6 Section 4.3.2 e.g. repeat spirometry or laboratory tests. However, to achieve the objectives of the research, these discretionary follow up visits will not be considered part of the trial data. |
|
| 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 | 4 |
| 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 | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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