Clinical trial NCT05172050: Multicenter Double Blind, Parallel-group Phase 2/3 Trial, to Study Raloxifene in Adult COVID-19 Patients.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: SARS CoV 2 Infection
Keywords: COVID-19
SARS-CoV-2
severe pneumonia
pneumonia
Lead sponsor: Dompé Farmaceutici S.p.A
Sponsor class: INDUSTRY
First posted: 2021-12-29
Enrollment: 61
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, adaptive, double-blind, randomized, placebo controlled, double blind, parallelgroup, to study efficacy and safety, with the following adaptive components:

* Parallel multi-arms (2 interventional arms and 1 placebo control arm);
* A 2-stage sequential design (1 interim analysis + 1 final analysis);
* Sample size re-calculation at interim stage;
* Stopping rule for efficacy or futility at interim stage.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Subject autonomously provides informed consent prior to initiation of any study procedures
2. Males and females ≥ 40 years old
3. 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
4. Agrees to the collection of nasopharyngeal swabs and venous blood samples per protocol
5. Has laboratory-confirmed SARS-CoV-2 infection as determined by an approved molecular test (PCR) in Europe within 10 days at the screening time
6. 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
7. No need of supplemental oxygen therapy, mechanical ventilation
8. 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:

   1. Hormonal contraception, systemic, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit until 30 days after final visit
   2. 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
   3. A male sexual partner who agrees to use a male condom with spermicide
   4. A sterile sexual partner

Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year will be admitted. For all female subjects, with child-bearing potential, pregnancy test result must be negative before first drug intake on T7 and T14.

Exclusion Criteria:

1. Being totally asymptomatic at the screening time
2. Requires supplemental oxygen therapy or mechanical ventilation
3. Being already under raloxifene or other SERM treatment for another medical condition at the time of randomization
4. 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)
5. Clinically significant abnormal physical findings which could interfere with the objectives of the study
6. Diseases:

   1. history of stroke and/or venous thromboembolism;
   2. known moderate / severe renal impairment: Chronic Kidney Disease (CKD) stage 3 or higher;
   3. known liver disease (Child-Pugh Class A or higher);
   4. presence of known hypoalbuminemia;
   5. endometrial bleeding;
   6. signs or symptoms of endometrial cancer
7. Autoimmune diseases receiving therapy at the time of randomization
8. Risk of venous thrombosis or any condition/disease that could bring to an extended period of immobilization
9. Ascertained or presumptive hypersensitivity to the active principles (raloxifene) and/or excipients or allergic reactions in general, which the Investigator considers may affect the outcome of the study
10. Medications: in particular cholestyramine (or any ion exchange resin), medications used in treatment of early or advanced breast cancer (including adjuvant therapy), warfarin, any drug that cannot be coadministered with the experimental compound
11. Pregnancy:

    1. positive or missing pregnancy test before first drug intake or day 1;
    2. pregnant or lactating women;
12. Women of childbearing potential and fertile men who does not agree to use at least one primary form of contraception for the duration of the study.

Primary outcomes:
measure: Number of Participants With Undetectable SARS-CoV-2 at PCR at Day 7 After Randomization in the FAS
timeFrame: At Day 7
measure: Number of Participants Not Requiring Oxygen Therapy and/or Mechanical Ventilation at Day 14 After Randomization in the FAS
timeFrame: At Day 14
Secondary outcomes:
measure: Number of Participants With Undetectable SARS-CoV-2 at PCR at Days 14 and 28 After Randomization in the FAS
timeFrame: At days 14 and 28 after randomization
measure: Number of Participants Not Requiring Oxygen Therapy and/or Mechanical Ventilation at Day 7 an d at Day 28 in the FAS
timeFrame: At days 7 and 28
measure: Number of Patients in Each National Early Warning Score (NEWS) Category in the FAS
timeFrame: At days 7, 14, 28
measure: Mean Value of National Early Warning Score (NEWS) Category in the FAS
timeFrame: At days 7, 14, 28 after randomization
measure: Number of Hospitalized Participants Who at the Beginning of the Study Were at Domicile Isolation After Randomization in the FAS
timeFrame: At days 7, 14, 28
measure: Number of Participants Admitted to Intensive Care After Randomization in the FAS
timeFrame: At days 7,14 ,28
measure: Number of Survivors in the FAS
timeFrame: At days 7, 14, 28
measure: Quality of Life Questionnaire (EQ-5D-5L) at 3 Months After Randomization - EQ-5D Descriptive System
timeFrame: At month 3 After Randomization
measure: Quality of Life Questionnaire (EQ-5D-5L) at 3 Months After Randomization - EQ VAS
timeFrame: At month 3 After Randomization
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
city: Caluire-et-Cuire
country: France
facility: Clinique de l'infirmerie protestante de Lyon
city: Le Puy-en-Velay
country: France
facility: CH Emile Roux le Puy en Velay
city: Troyes
country: France
facility: Centre Hospitalier de Troyes
city: Bergamo
country: Italy
facility: Humanitas Gavazzeni
city: L'Aquila
country: Italy
facility: Ospedale San Salvatore
city: Napoli
country: Italy
facility: AO dei Colli (Ospedale Monaldi)
city: Roma
country: Italy
facility: INMI Lazzaro Spallanzani
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
Study officials:
affiliation: Dompé Farmaceutici
name: Francesco Sergio, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Nicastri E, Marinangeli F, Pivetta E, Torri E, Reggiani F, Fiorentino G, Scorzolini L, Vettori S, Marsiglia C, Gavioli EM, Beccari AR, Terpolilli G, De Pizzol M, Goisis G, Mantelli F, Vaia F, Allegretti M; Raloxifene Territorial Health COVID19 STUDY GROUP. A phase 2 randomized, double-blinded, placebo-controlled, multicenter trial evaluating the efficacy and safety of raloxifene for patients with mild to moderate COVID-19. EClinicalMedicine. 2022 Jun;48:101450. doi: 10.1016/j.eclinm.2022.101450. Epub 2022 May 12.