A Phase 2 Study of RTB101 as COVID-19 Post-Exposure Prophylaxis in Older Adults

• ClinicalTrials.gov Identifier: NCT04584710
• Recruitment Status: Active, not recruiting
• First Posted: October 14, 2020
• Last Update Posted: February 9, 2021
• Sponsor: Restorbio Inc.
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): Restorbio Inc.

Tracking Information

• First Submitted Date: October 8, 2020
• First Posted Date: October 14, 2020
• Last Update Posted Date: February 9, 2021
• Actual Study Start Date: October 13, 2020
• Estimated Primary Completion Date: February 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 9, 2020)

To determine the length of time from date of receipt of a positive SARS-CoV2 test result to date of first dose of study drug in asymptomatic adults age ≥ 65 years [ Time Frame: Beginning of randomization through Week 2 ]

The number of days from the date of receipt of a positive SARS-CoV-2 swab test result to the date of first dose of study drug in asymptomatic subjects who:

• have SARS-CoV-2 detected on a surveillance nasal or nasopharyngeal swab OR
• live in the same house or apartment as someone who has laboratory-confirmed symptomatic COVID-19

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 9, 2020)

• To determine the feasibility of using an eDiary to assess study drug compliance in the study drug population [ Time Frame: Beginning of randomization through Week 2 ]
  Study drug compliance determined from the number of capsules of study drug taken by the subject based on data reported in an eDiary
• To determine the feasibility of using an eDiary to assess study drug compliance in the study drug population [ Time Frame: Beginning of randomization through Week 2 ]
  Study drug compliance determined from the number of capsules of study drug taken by the subject based on data from twice weekly phone calls
• To determine the feasibility of using an eDiary to assess study drug compliance in the study drug population [ Time Frame: Beginning of randomization through Week 2 ]
  Study drug compliance determined from the number of capsules of study drug taken by the subject based on a pill count done by phone when subjects complete study drug treatment
• To determine the feasibility of using an eDiary to assess COVID-19 symptoms in the study population [ Time Frame: From time of first dose through Week 3 ]
  Incidence and severity of COVID-19 symptoms based on data reported in an eDiary
• To determine the feasibility of using an eDiary to assess COVID-19 symptoms in the study population [ Time Frame: From time of first dose through Week 3 ]
  Incidence and severity of COVID-19 symptoms based on data from twice weekly phone calls
• To assess the incidence of treatment-emergent of AEs and SAEs in subjects assigned to RTB101 as compared to placebo [ Time Frame: From time of first dose through Week 3 ]
  Safety and tolerability will be assessed by report of AE/SAEs from first dose of study drug through Week 3
• To determine the percentage of subjects treated with RTB101 as compared to placebo who develop symptomatic laboratory-confirmed COVID-19 from first dose through Day 14 [ Time Frame: From time of first dose through Week 2 ]
  The percentage of subjects who have SARS-CoV-2 detected on nasal or nasopharyngeal swab and who develop 2 or more concurrent symptoms of COVID-19 from first dose of study drug through Day 14
• To determine the percentage of subjects treated with RTB101 as compared to placebo who die from any cause from first dose of study drug through Day 14 and 21 [ Time Frame: From time of first dose through Week 3 ]
  The percentage of subjects who die from any cause from first dose of study drug through Day 14 and 21
• To determine the percentage of subjects treated with RTB101 as compared to placebo who develop laboratory-confirmed COVID-19 from first dose through Day 14 and are subsequently hospitalized for any reason through Day 21 [ Time Frame: From time of first dose through Week 3 ]
  The percentage of subjects who develop laboratory-confirmed COVID-19 from first dose of study drug through Day 14 and are subsequently hospitalized for any reason through Day 21
• To determine the percent of subjects treated with RTB101 or placebo who have laboratory-confirmed SARS-CoV-2 infection regardless of symptoms from first dose of study drug through Days 7, 14, 21. [ Time Frame: From time of first dose through Week 3 ]
  The percentage of subjects who have SARS-CoV-2 detected on nasal or nasopharyngeal swab regardless of symptoms from first dose of study drug through Day 7, 14, and 21 among subjects who are not SARS-CoV-2 positive at screening or baseline

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 2 Study of RTB101 as COVID-19 Post-Exposure Prophylaxis in Older Adults
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Phase 2a Study of RTB101 as COVID-19 Post-Exposure Prophylaxis in Adults Age ≥65 Years
• Brief Summary: The proposed trial will obtain preliminary data on the feasibility of studying RTB101 as compared to placebo for COVID-19 post-exposure prophylaxis in adults age ≥ 65 years to inform the design of a subsequent pivotal trial.
• Detailed Description: The RTB101-211 study is a Randomized, Double-Blind, Placebo-Controlled Phase 2a Study of RTB101 as COVID-19 Post-Exposure Prophylaxis in Asymptomatic Adults Age ≥65 Years who: have SARS-CoV-2 detected on a surveillance nasal or nasopharyngeal swab OR live in the same house or apartment as someone who has laboratory-confirmed symptomatic COVID-19. The study is designed to obtain study feasibility data for RTB101 in an unbiased fashion and will inform the design of a subsequent pivotal trial.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Covid19

Intervention

• Drug: RTB101
  Oral RTB101 10 mg hard gelatin capsule once daily for 2 weeks
  Other Names:

  • Dactolisib
  • BEZ235
• Drug: Placebo
  Oral matching placebo once daily for 2 weeks
  Other Name: Placebo capsule

Study Arms

• Experimental: 10 mg daily RTB101

  RTB101

  TORC1 inhibitor

  Intervention: Drug: RTB101
• Placebo Comparator: Placebo
  Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: October 9, 2020): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 2021
• Estimated Primary Completion Date: February 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

1. Informed consent must be obtained from the subject before any assessment is performed.

2. Adults (male and female) aged 65 years and over who are asymptomatic but:

   1. have SARS-CoV-2 detected during surveillance nasal or nasopharyngeal swab testing OR
   2. live in the same house or apartment as someone who has laboratory-confirmed symptomatic COVID-19 .
3. 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.
4. Subject must be able to understand and comply with the requirements of the study including having internet access and an email account, willingness to answer an eDiary questionnaire on a personal electronic device each night, and willingness to answer the telephone questionnaires twice weekly

Exclusion Criteria:

1. Any subject who self-reports:

   1. As a current smoker, or stopped smoking within the past 6 months.
   2. As a previous smoker with a ≥10 pack year smoking history.
   3. Has a household member who currently smokes in the house.
2. Subjects with a medical history of chronic obstructive pulmonary disease (COPD), emphysema or chronic bronchitis requiring active treatment with a prescription medication
3. The subject has already had symptoms consistent with COVID-19 at screening.
4. Subjects who require chronic supplemental oxygen therapy at screening.
5. Subjects with current evidence of an unstable medical disorder including an unstable respiratory disorder, gastrointestinal disorder (including Child-Pugh class B and C hepatic impairment), renal disorder or hematologic disorder (including active leukemia) for which they have had an exacerbation of symptoms within the past month, or are undergoing a change in treatment.

6. The following cardiac conditions:

   1. Unstable angina pectoris
   2. History of myocardial infarction (MI), coronary bypass surgery, or any percutaneous coronary intervention (PCI) within 6 months prior to Screening
   3. Congestive heart failure requiring active treatment with a prescription medication
   4. Unstable or life-threatening cardiac arrhythmia

   a. Chronic stable atrial fibrillation is allowed

7. Subjects with a history of systemic autoimmune diseases (e.g., lupus, inflammatory bowel disease, rheumatoid arthritis, etc.).

   a. Psoriasis confined to the skin and eczema are allowed

8. Subjects receiving immunosuppressive therapy including chronic use of supraphysiologic steroids such as prednisone >10 mg daily (however, inhaled corticosteroids and acute use of higher doses of prednisone to treat conditions such as exacerbation of asthma or other acute conditions are allowed).
9. Subjects with an immunodeficiency disease, including a history of a positive human immunodeficiency virus (HIV) test result.
10. Subjects with a history of gastric bypass surgery.
11. Subjects who require treatment with strong CYP3A4 or CYP1A2 inhibitors or inducers, or subjects who require treatment with digoxin.
12. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 65 Years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04584710
• Other Study ID Numbers: RTB101-211; 3R01AG064802-02S1 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Restorbio Inc.
• Study Sponsor: Restorbio Inc.
• Collaborators: National Institute on Aging (NIA)

Investigators

• Study Director: Medical Monitor; Restorbio Inc.

• PRS Account: Restorbio Inc.
• Verification Date: February 2021