Clinical trial NCT03373903: Dose Finding Study to Determine if BEZ235 Alone or in Combination With RAD001 Decreases the Incidence of Respiratory Tract Infections in the Elderly
Official title: A Multicenter, Dose-finding Study to Determine if Oral BEZ235 Alone or in Combination With RAD001 Decreases the Incidence of Respiratory Tract Infections in Elderly Subjects
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Respiratory Tract Infections
Lead sponsor: Restorbio Inc.
Sponsor class: INDUSTRY
First posted: 2017-12-14
Enrollment: 652
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the efficacy, tolerability, and safety of BEZ235 alone and in combination with RAD001 to support further development to reduce the incidence of respiratory tract infections (RTIs) in elderly subjects.

Detailed description: This is a randomized, blinded, placebo-controlled, multicenter, parallel-group, dose finding 24-week study to assess the safety, tolerability and efficacy of up to 3 doses of BEZ235 alone and in combination with RAD001 as compared to placebo in elderly subjects who are at increased risk of respiratory tract infection related-morbidity and mortality. The study will be composed of up to a 6-week screening and run-in period, a 16-week treatment period and an 8-week follow-up period.

Eligibility criteria: Inclusion Criteria:

* Male and female subjects
* Age ≥ 85 years
* Age ≥ 65 and \< 85 years with one or more of the following conditions:

  * Asthma
  * Chronic Obstructive Pulmonary Disease (COPD)
  * Chronic bronchitis
  * Type 2 Diabetes Mellitus (T2DM)
  * Congestive Heart Failure (CHF) New York Heart Association (NYHA) functional classification I-II
  * Current smoker
  * One or more emergency room visits or hospitalizations for a RTI during the previous 12 months

Exclusion Criteria:

* Subjects with medically significant cardiac conditions including NYHA functional classification III-IV
* Subjects with Type I diabetes mellitus.
* Subjects with clinically significant underlying pulmonary disease other than asthma, GOLD Class I and II COPD or chronic bronchitis
* 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, cervical carcinoma in situ, breast cancer localized to the breast.
* Subjects with any one of the following:

  * hemoglobin \< 10.0 g/dL for males and \< 9.0 for females
  * white blood cell (WBC) count \< 3,500/mm3,
  * neutrophil count \< 2,000/mm3
  * platelet count \< 125,000/mm3
* Subjects with a history of a systemic autoimmune disease or receiving immunosuppressive therapy
* Recent surgery other than minor skin surgery
* Liver disease or liver injury
* History or presence of impaired renal function
* History of immunodeficiency diseases
* Subjects with active infection
* Subjects with a Mini Mental Status Examination (MMSE) score \<24 at screening.
* Significant illness (based on the subject's medical history and the clinical judgement of the investigator) which has not resolved within two (2) weeks prior to initial dosing.

Primary outcomes:
measure: The percentage of subjects with 1 or more laboratory-confirmed RTIs through Week 16
timeFrame: 16 weeks
Secondary outcomes:
measure: Percent of subjects who develop one or more RTIs through week 16
timeFrame: 16 weeks
measure: The rate of RTIs/person through week 16
timeFrame: 16 weeks
measure: The rate of RTIs per person through week 24
timeFrame: 24 weeks
measure: The percentage of subjects with 1 or more laboratory-confirmed RTIs through week 24
timeFrame: 24 weeks
measure: Peak Plasma Concentration (Cmax)
timeFrame: 8 weeks
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Wichita
country: United States
facility: Heartland Research Associates
state: Kansas
Study officials:
affiliation: Restorbio Inc.
name: Sarb Shergill, PhD
role: STUDY_DIRECTOR
References:
citation: Mannick JB, Teo G, Bernardo P, Quinn D, Russell K, Klickstein L, Marshall W, Shergill S. Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials. Lancet Healthy Longev. 2021 May;2(5):e250-e262. doi: 10.1016/S2666-7568(21)00062-3. Epub 2021 May 6.