| 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 |
|
| 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 | 16.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10022000 |
| E.1.2 | Term | Influenza |
| 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 |
| The primary objective of the study is to evaluate the reduction in AUC of virus load from the nasopharyngeal mucosa as measured by quantitative PCR, in the CT-P27 treatment groups compared to placebo, post Viral Challenge, and post virus shedding. |
|
| E.2.2 | Secondary objectives of the trial |
Efficacy:
- reduction in total AUC influenza composite symptoms post Viral Challenge and in the incidence of influenza infection.
Pharmacokinetics:
- AUC0-last, Cmax, Cmin, tmax, t1/2, mean residence time, clearance and volume of distribution to 36 days post-infusion.
Safety:
- To investigate the potential for the development of viral resistance.
To evaluate:
- incidence, severity, seriousness and relatedness of AEs
- vital signs
- 12- lead ECG
- clinical blood safety analysis
- spirometry
- incidence and severity of physical examination findings by day and overall postchallenge.
- toxicity
- hypersensitivity |
|
| 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 the medical history, physical examination, and routine laboratory tests as determined by the Investigator at a screening evaluation.
3. A total body weight ≥50 kg and a body mass index (BMI) of >18 kg/m2. If the BMI is above 30 kg/m2, the subject may be included if the waist measurement is less than 102 cm (male), or less than 88 cm (female).
4. The following criteria are applicable to partners in a relationship where the partners are of the opposite sex (i.e. the criteria do not apply to those in a same sex relationship):
(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 screening (from signing the informed consent form), and continuing for 3 months after the end of the study.
(b) In addition, male subjects must not donate sperm from screening (from signing the informed consent form), and for 3 months after the end of the study.
(c) Female subjects must:
- be post-menopausal females- defined as:
- aged over 45 years with at least 1 year of amenorrhoea and levels of follicle stimulating hormone (FSH) over 20 IU/L or
- aged over 50 years with at least 2 years of amenorrhoea.
or,
- have documented status as surgically sterile or post hysterectomy,
or,
- if of childbearing potential, must have a negative serum pregnancy test at screening 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 continuing for 3 months after the end of the study.
Acceptable forms of effective contraception include:
- Established (i.e. a minimum of 2 weeks prior to admission) 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].
- True abstinence: When this is in line with the preferred and usual lifestyle of the
subject. [Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation
methods) and withdrawal are not acceptable methods of contraception].
5. An informed consent document voluntarily signed and dated by the subject, and the Investigator.
6. Sero-suitable for the challenge virus. |
|
| E.4 | Principal exclusion criteria |
1. Significant history of any tobacco use at any time.
2. Pregnancy within 6 months prior to the study or who have a positive pregnancy test at any point.
Females intending to become pregnant within 3 months of drug administration or placebo or males with female partners intending to become pregnant within 3 months of drug administration.
3. Any history or evidence of any clinically significant cardiovascular, dermatological, gastrointestinal, endocrinological, haematological, hepatic, immunological, metabolic, urological, neurological, psychiatric, renal, and/or other major disease that may interfere with a subject completing the study.
a) Eczema/atopic dermatitis: subjects with clinically mild eczema/atopic dermatitis may be included.
b) Psoriasis: Subjects with a diagnosis of psoriasis by a dermatologist will be excluded.
c) 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.
Any concurrent serious illness (e.g., severe COPD, history of malignancy other than basal cell carcinoma within 5 years of initial diagnosis or with evidence of recurrence) that may interfere with a subject completing the study.
4. Abnormal pulmonary function as evidenced by the responses to the screening questions and/or clinically significant abnormalities in spirometry.
5. History or evidence of autoimmune disease or known immunodeficiency of any cause with the exception of eczema/atopic dermatitis.
6. History of asthma, COPD, pulmonary hypertension, reactive airway disease, or chronic lung condition.
7. Childhood asthma before the age of 12 years is acceptable provided the subject is asymptomatic. Subjects with a single episode of wheezing after age 12 (lasting less than 8 weeks) can be included provided the episode is more than 4 years ago and did not require a hospital admission and/or oral steroids.
8. Positive HIV, active hepatitis A, B, or C test.
9. Significant abnormality altering the anatomy of the nose or nasopharynx.
10. Clinically significant history of epistaxis.
11. Nasal or sinus surgery within 6 months.
12 Recurrent history of fainting.
13. 12-lead ECG recording with clinically relevant signs of pathology and conduction disturbances.
14. Confirmed positive test for drugs of abuse deemed to be clinically significant.
15. Venous access deemed inadequate for the phlebotomy and cannulation.
16. Known allergies to the excipients in the challenge virus or influenza treatments (i.e., oseltamivir) or antibiotics in two or more classes. Known history of allergy or reaction to any component of the investigational product
17. Health care workers who work in units with severely immuno-compromised patients.
18. Presence of household member or close contact who:
- has known immunodeficiency
- receiving immunosuppressant medication
- undergoing or soon to undergo cancer chemotherapy
- has been diagnosed with emphysema, COPD, or other severe lung disease
- has received a bone marrow or solid organ transplant
- resides in a nursing home.
19. Evidence of vaccinations within the 3 weeks prior to inoculation
- Intention to receive any vaccination(s) before the last follow up visit at 36 days post-infusion
20. Those employed or immediate relatives of those employed at RVL or the Sponsor.
21. Receipt of blood or blood products, or loss of 450 mL or more of blood during the 3 months prior to inoculation.
22. Use within 7 days prior to inoculation/dosing of any other medication or product, for symptoms of hay fever, rhinitis, nasal congestion or respiratory tract infections including the use of nasal steroids.
23. Previous receipt of IV monoclonal antibodies.
- Receipt of any investigational drug within 3 months prior to inoculation.
- Receipt of more than 3 investigational drugs within the previous 12 months.
- Prior inoculation with the same strain of respiratory virus.
- Prior inoculation with a respiratory virus within 1 year prior to the day of inoculation/first dosing with IMP.
- Prior participation in another Human Viral Challenge Study in the preceding 12 months taken from the date of inoculation in the previous study to the date of expected inoculation in this study.
24. Receipt of systemic glucocorticoids or systemic antiviral drugs within 6 months prior to inoculation.
- Receipt of any systemic chemotherapy agent, immunoglobulins (Igs) or any other cytotoxic or immunosuppressive drugs at any time.
25. Presence of significant respiratory symptoms existing on the day of inoculation or dosing.
- History suggestive of respiratory infection within 14 days prior to admission to the unit.
26. Female subject who is lactating
27. 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 AUC of post-challenge nasopharyngeal viral load measured by quantitative PCR of nasopharyngeal swab, post Viral Challenge to the last assessment day in quarantine. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Days 1-8 (tid, 8 h intervals), (9). |
|
| E.5.2 | Secondary end point(s) |
Efficacy. Treatment groups versus placebo for reduction in total AUC influenza composite symptoms post Viral Challenge and reduction in the incidence of influenza infection.
Pharmacokinetics. AUC0-last, Cmax, Cmin, tmax, t1/2, mean residence time (MRT), clearance (CL) and volume of distribution (Vz ) for treatment groups.
Safety. Evaluate treatment groups compared to placebo group for incidence, severity, seriousness and relatedness of AEs, vital signs, 12- lead ECG, clinical blood safety analysis, spirometry, incidence and severity of physical examination findings by day and overall postchallenge, toxicity, hypersensitivity. Potential for development of viral resistance. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy. Influenza symptoms days (-2), -1-8 (tid), 9. Tissue count & mucus weight day 0 (pre-challenge), 1-9. Influenza infection days 1-8 , (9).
PK. Serum samples day -2, 0 (pre-Viral Challenge, pre-infusion (-60 min), post-infusion at 0, 1, 6, 12, 24, 48 h, days 6, 14, 28, 36.
Safety. AEs from screening. Bloods at screening, days -2, (-1), (1-7), 8, (9), 14, 28, 36. ECG at screening & days -2, (-1), 0, (1-5), 8, (9), 14, 28, 36. Spirometry at screening, days -2, (-1), 0, 1-9, 14, 28, 36. Vital signs at screening, (-2), -1-8 (tid), 9, 14, 28, 36. Physical exam at screening, days -2-9, 14, 28, 36. Toxicity at pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 24 and 48 h post infusion. Hypersensitivity at pre-dose, 0.25, 0.5, 1, 1.5, 2, 3 , 4 h post infusion. Viral resistance day 1-9. |
|
| 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 | 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 | Yes |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | 17 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| 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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