Multicenter, Adaptive, Randomized, Placebo-controlled, Double Blind, Parallel-group Phase 2/3 Trial, to Study Efficacy and Safety of Two Doses of Raloxifene in Adult Paucisymptomatic COVID-19 Patients.
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Dompé Farmaceutici S.p.A
- Enrollment
- 61
- Locations
- 11
- Primary Endpoint
- Number of Participants Not Requiring Oxygen Therapy and/or Mechanical Ventilation at Day 14 After Randomization in the FAS
Overview
Brief Summary
The objective of the study is to evaluate the efficacy and safety of two different doses of raloxifene orally administered compared to placebo in patients with early diagnosis of paucisymptomatic COVID-19.
Primary objectives:
- Evaluation of the effectiveness of therapy in reducing the proportion of subjects who still have viruses in the upper airways after 7 days of therapy
- Evaluation of the effectiveness of therapy in reducing the proportion of subjects who requires supplemental oxygen therapy and/or mechanical ventilation within 14 days of starting therapy
Secondary objectives:
- Evaluation of the effectiveness of therapy in reducing the proportion of subjects who still have viruses in the upper airways after 14 and 28 days of therapy
- Evaluation of the effectiveness of therapy in reducing the proportion of subject patients who requires supplemental oxygen therapy and/or mechanical ventilation within 7 or 28 days of starting therapy
- 7, 14 and 28 days drug safety and tolerability profile
- Assessment of body temperature, blood and biochemical parameters between T0 and T28
Detailed Description
The study is a phase 2/3, multicenter, adaptive, randomized, placebo-controlled, double blind, parallel-group study to evaluate efficacy and safety of two doses of raloxifene in adult paucisymptomatic COVID-19 patients.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Masking Description
Appearance, including packaging and labelling, of the investigational medicinal product (IMP, capsules, packaging) will not allow to recognize actual treatment (either raloxifene or placebo).
Eligibility Criteria
- Ages
- 40 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subject autonomously provides informed consent prior to initiation of any study procedures
- •Males and females ≥ 40 years old
- •Understands and agrees to comply with planned study procedures, has the availability of an email address as well as an Internet connection at domicile location
- •Agrees to the collection of nasopharyngeal swabs and venous blood samples per protocol
- •Has laboratory-confirmed SARS-CoV-2 infection as determined by an approved molecular test (PCR) in Europe within 10 days at the screening time
- •Patient paucisymptomatic who complains at the screening time at least one of the following symptoms mild to moderate: fever, dyspnea, headache, cough, dysgeusia, conjunctivitis, vomiting, diarrhea, anosmia, muscle or body aches or other symptoms which in the opinion of the Investigator are part of the COVID-19 clinical picture
- •No need of supplemental oxygen therapy, mechanical ventilation
- •Females of child-bearing potential and with an active sexual life must not wish to get pregnant within 30 days after the end of the study and must be using at least one of the following reliable methods of contraception:
- •Hormonal contraception, systemic, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit until 30 days after final visit
- •A non-hormonal intrauterine device \[IUD\] or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit until 30 days after final visit
Exclusion Criteria
- •Being totally asymptomatic at the screening time
- •Requires supplemental oxygen therapy or mechanical ventilation
- •Being already under raloxifene or other SERM treatment for another medical condition at the time of randomization
- •Being concurrently involved in another trial with IP or participation in any clinical trial with IP for 1 months before this study. The 1-month interval is calculated as the time between the last visit of the previous study and the first day of the present study (date of the informed consent signature)
- •Clinically significant abnormal physical findings which could interfere with the objectives of the study
- •history of stroke and/or venous thromboembolism;
- •known moderate / severe renal impairment: Chronic Kidney Disease (CKD) stage 3 or higher;
- •known liver disease (Child-Pugh Class A or higher);
- •presence of known hypoalbuminemia;
- •endometrial bleeding;
Arms & Interventions
Group 1: Raloxifene 60 mg
After an administration of two oral doses in the first day of treatment (one dose in the morning and one dose in the evening, each dose administered with 2 capsules containing 60 mg of the active substance or placebo), a single daily oral dose of raloxifene 60 mg was administered; the treatment was taken by the patients for two weeks.
Intervention: Raloxifene (Drug)
Group 2: Raloxifene 120 mg
After an administration of two oral doses in the first day of treatment (one dose in the morning and one dose in the evening, each dose administered with 2 capsules containing 60 mg of the active substance or placebo), a single daily oral dose of raloxifene 120 mg was administered; the treatment was taken by the patients for two weeks.
Intervention: Raloxifene (Drug)
Group 3: Placebo.
After an administration of two oral doses in the first day of treatment (one dose in the morning and one dose in the evening, each dose administered with 2 capsules containing placebo), a single daily oral dose of placebo (2 capsules guarantee the blinding design) was administered; the treatment was taken by the patients for two weeks.
Intervention: Placebo (Other)
Outcomes
Primary Outcomes
Number of Participants Not Requiring Oxygen Therapy and/or Mechanical Ventilation at Day 14 After Randomization in the FAS
Time Frame: At Day 14
Proportion of participants who does not require supplemental oxygen therapy (NEWS ≤ 2) and/or mechanical ventilation. NEWS is a system for scoring the physiological measurements that are routinely recorded at the patient's bedside. NEWS uses six physiological measurements. An additional two points are added if the patient is receiving oxygen therapy. The total possible score ranges from 0 to 20. If collected NEWS score \> 2 or mechanical ventilation with result "Yes" then the response was considered as "Required". If collected NEWS score ≤ 2 and mechanical ventilation with result "No" then the response was considered as "Not Required" (if both NEWS score and mechanical ventilation were missing, patient was considered as missing).
Number of Participants With Undetectable SARS-CoV-2 at PCR at Day 7 After Randomization in the FAS
Time Frame: At Day 7
Number of participants who, after an approved molecular test (PCR), were not detected as SARS-CoV2 positive. Based on Approved molecular test (PCR) result at day 7, the responses were considered as "detectable" if PCR result was "Positive" otherwise "undetectable" if PCR result was "Negative" .
Secondary Outcomes
- Number of Hospitalized Participants Who at the Beginning of the Study Were at Domicile Isolation After Randomization in the FAS(At days 7, 14, 28)
- Number of Participants With Undetectable SARS-CoV-2 at PCR at Days 14 and 28 After Randomization in the FAS(At days 14 and 28 after randomization)
- Number of Patients in Each National Early Warning Score (NEWS) Category in the FAS(At days 7, 14, 28)
- Mean Value of National Early Warning Score (NEWS) Category in the FAS(At days 7, 14, 28 after randomization)
- Number of Participants Not Requiring Oxygen Therapy and/or Mechanical Ventilation at Day 7 an d at Day 28 in the FAS(At days 7 and 28)
- Number of Participants Admitted to Intensive Care After Randomization in the FAS(At days 7,14 ,28)
- Number of Survivors in the FAS(At days 7, 14, 28)
- Quality of Life Questionnaire (EQ-5D-5L) at 3 Months After Randomization - EQ-5D Descriptive System(At month 3 After Randomization)
- Quality of Life Questionnaire (EQ-5D-5L) at 3 Months After Randomization - EQ VAS(At month 3 After Randomization)