Dose Finding Study to Determine if BEZ235 Alone or in Combination With RAD001 Decreases the Incidence of Respiratory Tract Infections in the Elderly

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Respiratory Tract Infections
• Intervention / Treatment: Other: Placebo; Drug: BEZ235; Drug: BEZ235 plus everolimus (RAD001)

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.

• Study Type: Interventional
• Enrollment (Actual): 652
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Wichita, Kansas, United States, 67205
      • Heartland Research Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo once daily for 16 weeks	Other: Placebo; oral
EXPERIMENTAL: BEZ235 once daily for 16 weeks	Drug: BEZ235; oral
EXPERIMENTAL: BEZ235 twice daily for 16 weeks	Drug: BEZ235; oral
EXPERIMENTAL: BEZ235 plus RAD001 once daily for 16 weeks	Drug: BEZ235 plus everolimus (RAD001); Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The percentage of subjects with 1 or more laboratory-confirmed RTIs through Week 16	16 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent of subjects who develop one or more RTIs through week 16	16 weeks
The rate of RTIs/person through week 16	16 weeks
The rate of RTIs per person through week 24	24 weeks
The percentage of subjects with 1 or more laboratory-confirmed RTIs through week 24	24 weeks
Peak Plasma Concentration (Cmax)	8 weeks
Area under the plasma concentration versus time curve (AUC)	8 weeks

Collaborators and Investigators

• Sponsor: Restorbio Inc.
• Investigators: Study Director: Sarb Shergill, PhD, Restorbio Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 15, 2017
• Primary Completion (ACTUAL): May 3, 2018
• Study Completion (ANTICIPATED): July 1, 2018

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: December 11, 2017
• First Posted (ACTUAL): December 14, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 16, 2018
• Last Update Submitted That Met QC Criteria: May 11, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Infections; Communicable Diseases; Respiratory Tract Infections; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dactolisib; Everolimus
• Other Study ID Numbers: RTB-BEZ235-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No