A Phase 3 Study to Determine if RTB101 Prevents Clinically Symptomatic Respiratory Illness in the Elderly
Condition: Respiratory Tract Infections
MeSH terms: Respiratory Tract Infections
Intervention: Dactolisib; Placebo
Intervention description: TORC1 inhibitor; Placebo
Intervention MeSH terms: Dactolisib
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 1024.0
Sex: All
Minimum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      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.
    

Eligibility criteria:

        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
             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.

          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.

        Exclusion Criteria:

          1. 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

          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/1.73m2), or hematologic disorders.

          5. 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

          6. 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.

          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:

               -  white blood cell (WBC) count <2.0 x103/microL.

               -  neutrophil count <1.0 x 103/microL.

               -  platelet count <75 x 103/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).