A Phase 3 Study to Determine if RTB101 Prevents Clinically Symptomatic Respiratory Illness in the Elderly

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3 Study to Determine if RTB101 Prevents Clinically Symptomatic Respiratory Illness in the Elderly

Conditions
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Respiratory Tract Infections

Intervention / Treatment
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* Drug: Dactolisib
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. 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). Subjects must be ≥65 years of age. 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. Females must be post-menopausal. Women are considered postmenopausal and not of childbearing 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 6 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 childbearing potential. 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. Subject must weigh at least 40 kg. 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. Exclusion Criteria: Any subject who: Is a current smoker as assessed by medical history or a positive serum cotinine test (or positive urine cotinine test if serum cotinine testing is unavailable) at Screening. Stopped smoking ≤1 year prior to Screening. Is a previous smoker with a ≥10 pack year smoking history. Has a household member who currently smokes in the house 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.). Subjects with a Mini Mental Status Examination (MMSE) score <24 at Screening. 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/1.73m2), or hematologic disorders. The following cardiac conditions: Unstable angina pectoris or acute ischemic changes on ECG at Screening or Baseline History of myocardial infarction (MI), coronary bypass surgery, or any percutaneous coronary intervention (PCI) within 6 months prior to Screening New York Heart Association functional classification IIIIV congestive heart failure Unstable or life-threatening cardiac arrhythmia, chronic stable atrial fibrillation is allowed. QTcF>480 msec at Screening or Baseline Subjects with history of malignancy in any organ system within the past 5 years, EXCEPT for the following: Localized basal cell or squamous cell carcinoma of the skin. Prostate cancer confined to the gland (AJCC stage T2N0M0 or better). Cervical carcinoma in situ. Breast cancer localized to the breast. 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. 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). Subjects with Type I diabetes mellitus. Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further evaluation. Subjects with any one of the following during Screening: white blood cell (WBC) count <2.0 x103/microL. neutrophil count <1.0 x 103/microL. platelet count <75 x 103/microL.. Subjects with a history of alcohol or drug abuse within 2 years of the Screening visit. 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. Subjects with a history of immunodeficiency diseases, including a positive human immunodeficiency virus (HIV) test result. Infection with Hepatitis B virus (HBV) or Hepatitis C virus (HCV). Subjects who require treatment with strong CYP3A4 or CYP1A2 inhibitors or inducers, or subjects who require treatment with digoxin. 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. Subjects who have received an organ transplant. Subjects who previously received treatment with RTB101 in another clinical study (e.g., CBEZ235Y2201, RTB-BEZ235-202, or RTB-101-203).

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dactolisib 10mg once daily<br> | Drug: Dactolisib<br>* TORC1 inhibitor<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Clinically Symptomatic Respiratory Illness | 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 | Week 0-16 |