| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Clinically Symptomatic Respiratory Illness in the Elderly |
|
| E.1.1.1 | Medical condition in easily understood language |
| Respiratory illness associated with respiratory tract infections (RTIs) in the elderly. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| 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 purpose of this study is to determine if RTB101 prevents clinically symptomatic respiratory illness in subjects ≥65 years of age. Subjects with clinically symptomatic respiratory illness are defined as subjects with symptoms consistent with a RTI based on prespecified diagnostic criteria.
Primary objective of the study is to determine if RTB101 as compared to placebo decreases the percentage of subjects with clinically symptomatic respiratory illness (with or without an associated laboratory-confirmed pathogen) through Week 16. |
|
| E.2.2 | Secondary objectives of the trial |
Determination through Week 16 if RTB101 as compared to placebo:
1)decreases the percentage of subjects with clinically symptomatic respiratory illness associated with ≥1 laboratory-confirmed pathogen(s)
2)on the rate of clinically symptomatic respiratory illnesses associated with specific laboratory-confirmed viruses (coronaviruses, hMPV, HRV/enterovirus, adenovirus, influenza A and B virus, parainfluenza viruses, and RSV)
3)decreases the rate of clinically symptomatic respiratory illness (with or without an associated laboratory-confirmed pathogen)
4)decreases the rate of clinically symptomatic respiratory illnesses associated with ≥1 laboratory-confirmed pathogen(s)
5)decreases time to alleviation of moderate and severe respiratory illness symptoms due to clinically symptomatic respiratory illness
6)decreases the percentage of subjects with severe symptoms due to clinically symptomatic respiratory illnesses
7)To assess the safety and tolerability of RTB101 through Week 20
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Written informed consent must be obtained before any assessment is performed.
2. Male and female subjects who, in the clinical judgement of the Investigator, are without unstable medical conditions defined as conditions that require acute medical intervention or ongoing adjustments of concomitant medications (as determined by medical history, current concomitant medications and laboratory test results at Screening, and physical examination, electrocardiogram (ECG) and vital signs at Screening and Baseline).
3. Subjects must be ≥65 years of age.
4. Subjects should require no or minimal assistance with self-care and activities of daily living. Subjects in assisted-living or long-term care residential facilities that provide minimal assistance are eligible.
5. Females must be post-menopausal. Women are considered postmenopausal and not of child bearing potential if they have had:
• 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) OR
• surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks prior to Screening. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment will she be considered not of child bearing potential.
6. Sexually active male subjects with a partner of child-bearing potential must be willing to wear a condom while on study drug and for 1 week after stopping study drug and should not father a child in this period. A condom is required to be used also by vasectomized men with a partner of child-bearing potential to prevent delivery of the drug via seminal fluid.
7. Subject must weigh at least 40 kg.
8. Subject must be able to communicate well with the Investigator, and to understand and comply with the requirements of the study including completing a daily eDiary at home.
|
|
| E.4 | Principal exclusion criteria |
1. Any subject who:
a. Is a current smoker as assessed by medical history or a positive serum cotinine test at Screening.
b. Stopped smoking ≤1 year prior to Screening.
c. Is a previous smoker with a ≥10 pack year smoking history.
d. Has a household member who currently smokes in the house.
2. Subjects with a medical history of clinically significant lung diseases other than asthma (e.g., chronic obstructive pulmonary disease (COPD), emphysema, interstitial pulmonary fibrosis (IPF), bronchiectasis, etc.).
3. Subjects with a Mini Mental Status Examination (MMSE) score <24 at Screening.
4. Subjects with current evidence of a serious and/or unstable medical disorder including cardiovascular, respiratory, gastrointestinal, renal (including subjects with an estimated glomerular filtration rate (eGFR) as estimated by the modified diet in renal disease (MDRD) GFR equation that is ≤30 mL/min/1.73sqm), or hematologic disorders.
5. The following cardiac conditions:
a. Unstable angina pectoris or acute ischemic changes on ECG at Screening or Baseline
b. History of myocardial infarction (MI), coronary bypass surgery, or any percutaneous coronary intervention (PCI) within 6 months prior to Screening
c. New York Heart Association functional classification III-IV congestive heart failure
d. Unstable or life-threatening cardiac arrhythmia
i. Chronic stable atrial fibrillation is allowed.
e. QTcF>480 msec at Screening or Baseline
6. Subjects with history of malignancy in any organ system within the past 5 years, EXCEPT for the following:
a. Localized basal cell or squamous cell carcinoma of the skin.
b. Prostate cancer confined to the gland (AJCC stage T2N0M0 or better).
c. Cervical carcinoma in situ.
d. Breast cancer localized to the breast.
7. Any RTI or acute significant illness (based on the subject’s medical history and the clinical judgement of the Investigator) which has not resolved at least two (2) weeks prior to Baseline.
8. Subjects with a history of systemic autoimmune diseases (e.g., lupus, inflammatory bowel disease, rheumatoid arthritis, etc.), or receiving immunosuppressive therapy (such as mycophenolate, tacrolimus, cyclosporine, azathioprine, infliximab) including chronic use of prednisone >10 mg daily (however, inhaled corticosteroids and the acute use of higher doses of prednisone to treat conditions such as exacerbation of asthma or other acute conditions are allowed).
9. Subjects with Type I diabetes mellitus.
10. Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further evaluation.
11. Subjects with any one of the following during Screening:
a. white blood cell (WBC) count <2000/microL.
b. neutrophil count <1000/microL.
c. platelet count <75000/microL..
12. Subjects with a history of alcohol or drug abuse within 2 years of the Screening visit.
13. Subjects with any conditions affecting absorption, distribution, or metabolism of the study drug (e.g., inflammatory bowel disease, gastric or duodenal ulcers, or hepatic disease). For subjects with biochemical evidence of liver injury as indicated by abnormal liver function tests:
• Any single parameter of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase or serum bilirubin must not exceed 1.5 x upper limit of normal (ULN) in subjects who do not have Gilbert's syndrome. If the subject has a history of Gilbert’s syndrome, direct and indirect reacting bilirubin should be differentiated, and the direct bilirubin must be less than 1.5 x ULN.
•Any elevation above ULN of more than one parameter of ALT, AST, alkaline phosphatase or serum bilirubin will exclude a subject from participation in the study.
14. Subjects with a history of immunodeficiency diseases, including a positive human immunodeficiency virus (HIV) test result.
15. Infection with Hepatitis B virus (HBV) or Hepatitis C virus (HCV).
16. Subjects who require treatment with strong CYP3A4 or CYP1A2 inhibitors or inducers, or subjects who require treatment with digoxin.
17. Use of any other investigational medication or participation in any other investigational study within 5 half-lives of the investigational medication, or within 30 days, whichever is longer; or longer if required by local regulations.
18. Subjects who have received an organ transplant.
19. Subjects who previously received treatment with RTB101 in another clinical study (e.g., CBEZ235Y2201, RTB-BEZ235-202, or RTB-101-203).
20. Any study site employee or their family member are excluded. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The percentage of subjects with clinically symptomatic respiratory illness (with or without an associated laboratory-confirmed pathogen) beginning at least 3 days after the start of study drug treatment through Week 16 as assessed by pre-specified clinical diagnostic criteria.
A questionnaire was developed for this study and its content validated. Subjects self-report their symptoms in an eDiary. Frequent cold symptom entries will trigger a request to come in for an office visit for a nasal swab to detect pathogens (e.g., cold viruses). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Beginning at least 3 days after the start of study drug treatment through Week 16. Symptoms are collected via the eDiary daily by asking subjects to complete the respiratory symptom questionnaire each day in the evening. Subjects will come in for an unscheduled visit and get a nasal swab and other assessments if flu like symptoms are suspected, rapid influenza diagnostic test (RIDT), and Sputum gram stain. |
|
| E.5.2 | Secondary end point(s) |
1. percentage of subjects with 1 or more clinically symptomatic respiratory illnesses associated with ≥1 laboratory-confirmed pathogen(s) beginning at least 3 days after the start of study drug treatment through Week 16 as assessed by pre-specified clinical diagnostic criteria and respiratory pathogen PCR of nasopharyngeal swabs, sputum gram stain and culture, and/or rapid influenza diagnostic tests (RIDTs)
2. The rate of clinically symptomatic respiratory illnesses associated with specific laboratory-confirmed viruses (coronaviruses, hMPV, HRV/enterovirus, adenovirus, influenza A and B virus, parainfluenza viruses, and RSV) beginning at least 3 days after the start of study drug treatment through Week 16 as assessed by respiratory pathogen PCR of nasopharyngeal swabs and/or RIDTs.
3. The rate of clinically symptomatic respiratory illness (with or without an associated laboratory-confirmed pathogen) beginning at least 3 days after the start of study drug treatment through Week 16 as assessed by pre-specified clinical diagnostic criteria
4. The rate of clinically symptomatic respiratory illnesses associated with ≥ 1 laboratory-confirmed pathogen(s) beginning at least 3 days after the start of study drug treatment through Week 16 as assessed by pre-specified clinical diagnostic criteria and respiratory pathogen PCR of nasopharyngeal swabs, sputum gram stain and culture, and/or RIDTs
5. The time to alleviation of moderate and severe clinically symptomatic respiratory illness symptoms due to clinically symptomatic respiratory illness beginning at least 3 days after the start of study drug treatment through Week 16
6. The percentage of subjects with severe symptoms due to clinically symptomatic respiratory illnesses beginning at least 3 days after the start of study drug treatment through Week 16
7. Safety and tolerability will be assessed by report of adverse events (AE)/serious adverse events (SAEs), physical exam and ECG findings, and safety laboratory values least 3 days after the start of study drug treatment through Week 16 as assessed by pre-specified clinical diagnostic criteria
8. The rate of clinically symptomatic respiratory illnesses associated with ≥ 1 laboratory-confirmed pathogen(s) beginning at least 3 days after the start of study drug treatment through Week 16 as assessed by pre-specified clinical diagnostic criteria and respiratory pathogen PCR of nasopharyngeal swabs, sputum gram stain and culture, and/or RIDTs
9. The time to alleviation of moderate and severe clinically symptomatic respiratory illness symptoms due to clinically symptomatic respiratory illness beginning at least 3 days after the start of study drug treatment through Week 16
10. The percentage of subjects with severe symptoms due to clinically symptomatic respiratory illnesses beginning at least 3 days after the start of study drug treatment through Week 16
11. Safety and tolerability will be assessed by report of adverse events (AE)/serious adverse events (SAEs), physical exam and ECG findings, and safety laboratory values
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
All Secondary Endpoints 1 to 11 are evaluated beginning at least 3 days after the start of study drug treatment through Week 16.
|
|
| 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 | Yes |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 19 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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 | 7 |
| E.8.9.1 | In the Member State concerned days | 21 |
| 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 | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 21 |
Print
