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. |
|
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 |
This is an exploratory study and therefore objectives are not defined as primary and secondary. All objectives of this study are exploratory. These are listed here:
Part 1 Objectives
•To confirm the planned dose of Palivizumab to be given to participants in Part 2 •To assess safety of Palivizumab in healthy adults
Part 2 Objectives
•To estimate the margin and variance of prophylactic effect of Intravenous (IV) treatment with Palivizumab administered 1 day prior to inoculation in the RSV human challenge model in healthy adults compared to Placebo [assessed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR)]. •To estimate the margin and variance of prophylactic effect of IV treatment with Palivizumab administered 1 day prior to inoculation in the RSV human challenge model in healthy adults compared to Placebo [assessed by cell culture (pfu/mL)]. •To estimate the margin and variance of prophylactic effect of IV treatment with Palivizumab administered 1 day prior |
|
E.2.2 | Secondary objectives of the trial |
Please refer to section A10. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Please refer to Section 5.1 of the Protocol for full Inclusion criteria. Below is an abbreviated list:
1. Informed Consent 2. Aged between 18 and 55 years. 3. In good health with no history, or current evidence, of clinically significant medical conditions, and no clinically significant test abnormalities that will interfere with participant safety, as defined by medical history, physical examination, (including vital signs), Electrocardiogram (ECG), and routine laboratory tests as determined by the Investigator. 4. A documented medical history prior to enrolment. 5. Females of childbearing potential must have a negative pregnancy test prior to enrolment. 6. Female participants of childbearing potential must use one form of highly effective contraception. Hormonal methods must be in place from at least 2 weeks prior to the first study visit. The contraception use must continue until 30 days after the date of viral challenge/last dosing with IMP (whichever occurs last). b)Male participants 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 the investigational medicinal product (IMP) (whichever occurs last). c)Male participants 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). 7.For Part 2 of the study: Sero-suitable to the challenge virus, as defined in the study Analytical Plan.
|
|
E.4 | Principal exclusion criteria |
Please refer to Section 5.2 of the Protocol for full Inclusion criteria. Below is an abbreviated list:
1. History of, or currently active, symptoms or signs suggestive of upper or lower respiratory tract infection within 4 weeks prior to the first study visit. 2. a)Any history or evidence of any other clinically significant or currently active systemic comorbidities including psychiatric disorders (includes participants with a history of depression and/or anxiety). b)And/or other major disease that, in the opinion of the Investigator, may put the participant at undue risk, or interfere with a participant completing the study and necessary investigations. 3.Participants 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]). 4.A total body weight ≤ 50 kg and Body Mass Index (BMI) ≤18 kg/m2 and ≥30kg/m2. 5.Females who: a)Are breastfeeding, or b)Have been pregnant within 6 months prior to the study. 6.History of anaphylaxis-and/or a history of severe allergic reaction or significant intolerance to any food or drug, as assessed by the PI. 7.Venous access deemed inadequate for the phlebotomy and cannulation demands of the study. 8.a)For Part 2 of the study: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). b)Any clinically significant history of epistaxis (large nosebleeds) within the last 3 months of the first study visit and/or history of being hospitalized due to epistaxis on any previous occasion. c)Any nasal or sinus surgery within 3 months of the first study visit. 9.For Part 2 of the study: 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 (±3 days) Follow-up Visit). 10.Receipt of blood or blood products, or loss (including blood donations) of 470 mL or more of blood during the 3 months prior to the planned date of viral challenge/first dosing with IMP (whichever occurs first) or planned during the 3 months after the final visit. 11.a)Receipt of any investigational drug within 3 months prior to the planned date of viral challenge/first dosing with IMP (whichever occurs first). b)Receipt of three or more investigational drugs within the previous 12 months prior to the planned date of viral challenge/first dosing with IMP (whichever occurs first).
For Part 2 of the study: c)Prior inoculation with a virus from the same virus-family as the challenge virus. d)Prior participation in another human viral challenge study with a respiratory virus in the preceding 3 months, taken from the date of viral challenge in the previous study to the date of expected viral challenge in this study. 12. a) Confirmed positive test for drugs of abuse on first study visit. One repeat test allowed at PI discretion. b) History or presence of alcohol addiction, or excessive use of alcohol, or excessive consumption of xanthine containing substances. 13. For Part 2 of the study: A forced expiratory volume in 1 second (FEV1) < 80%. 14. Positive human immunodeficiency virus (HIV), active hepatitis A (HAV), B (HBV), or C (HCV) test. 15. Those employed or immediate relatives of those employed at hVIVO or the Sponsor. 16. Any other finding that, in the opinion of the Investigator, deems the participant unsuitable for the study.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
This is an exploratory study and therefore outcome measures / endpoints are not defined as primary and secondary. All objectives of this study are exploratory. These are listed here:
Part 1: Duration: Throughout (D-1 to D18)
•Evaluation of PK levels after intravenous administration of Palivizumab •Frequency and severity of Adverse Events (AEs) and serious AEs (SAEs) •Frequency and severity of Treatment Emergent Adverse Events (AEs) and serious AEs (SAEs) •Frequency and severity of drug related Treatment Emergent Adverse Events (AEs) and serious AEs (SAEs)
Part 2: Duration listed within each outcome measure description.
The margin and variance will be estimated as follows: •Area under the viral load-time curve (VL-AUC) of RSV-A Memphis 37b as determined by qRT-PCR on nasal samples collected twice daily starting two days post-viral challenge (Day +2) up to the end of quarantine. •Area under the viral load-time curve (VL-AUC) of RSV-A Memphis 37b as determined by cell culture on nasal samples collected twice daily starting two days post-viral challenge (Day +2) up to the end of quarantine. •Area under the total symptom score-time curve (TSS-AUC) collected daily in the participant symptom diary card starting one day post-viral challenge (Day +1) up to the end of quarantine. •Sum Total symptom score-time curve (TSS-Sum) collected daily in the participant symptom diary card starting one day post-viral challenge (Day +1) up to the end of quarantine. •Total weight of nasal discharge produced starting one day post viral challenge (Day +1) up to the end of quarantine. •Total number of tissues used by participants starting one day post viral challenge (Day +1) up to the end of quarantine. •Incidence of symptomatic RSV infection, as defined by: oIncidence of infection, and oAt least one grade 2 symptom from one or more respiratory categories from the participant symptom diary card. •Number of days with symptoms of grade 2 or more, starting one day post viral challenge (Day +1) up to the end of quarantine. •Peak symptom score defined by the maximum daily sum of Symptom score starting one day post viral challenge (Day +1) up to the end of quarantine. •Frequency and severity of Adverse Events (AEs) and serious AEs (SAEs) •Frequency and severity of Treatment Emergent Adverse Events (AEs) and serious AEs (SAEs) •Frequency and severity of drug related Treatment Emergent Adverse Events (AEs) and serious AEs (SAEs) •Palivizumab serum concentrations and serum PK parameters through study Day +28 •Nasal concentrations and serum PK parameters through study Day +28 •Anti-Palivizumab antibody (ADA) through Day 28
•Assessments of spirometry, PEF, and FOT •The average amount of instrument-assessed change for all participants who rate themselves as "a little better" or "somewhat better" The above endpoints may be explored in relation to the baseline status of volunteers and the response to treatment. Baseline status and response can be regarding, but not limited to: •Immune assays related to Palivizumab (e.g. IgG anti-F ELISA, PCA) •Baseline immunity to RSV •Response to Palivizumab treatment •Immune assays related to Palivizumab •RSV baseline immunity and immune responses to infection |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoints listed thin each outcome measure description.
|
|
E.5.2 | Secondary end point(s) |
This is an exploratory study and therefore outcome measures / endpoints are not defined as primary and secondary. All objectives of this study are exploratory. Please refer to section E5-1.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Please refer to section E5-1. |
|
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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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
|
|
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 | 3 |
E.8.9.1 | In the Member State concerned days | 19 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 19 |