Multicenter Double Blind, Parallel-group Phase 2/3 Trial, to Study Raloxifene in Adult COVID-19 Patients.

NCT ID: NCT05172050

Last Updated: 2023-12-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-22
• Study Completion Date: 2021-06-12

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.

Conditions

SARS CoV 2 Infection

Keywords

COVID-19; SARS-CoV-2; severe pneumonia; pneumonia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Raloxifene

Intervention Type: DRUG

Raloxifene was administered as 60 mg hard gelatine capsule(s) once a day. Starting from day 2 of treatment: one single capsule (plus one of placebo to guarantee the blinding) containing 60 mg raloxifene was administered in Group 1, and 2 capsules 60 mg each for a total of 120 mg in Group 2.

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.

Group Type: EXPERIMENTAL

Raloxifene

Intervention Type: DRUG

Raloxifene was administered as 60 mg hard gelatine capsule(s) once a day. Starting from day 2 of treatment: one single capsule (plus one of placebo to guarantee the blinding) containing 60 mg raloxifene was administered in Group 1, and 2 capsules 60 mg each for a total of 120 mg in Group 2.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo was administered orally once a day as 2 capsules (for maintaining the blinding design)

Interventions

Raloxifene

Raloxifene was administered as 60 mg hard gelatine capsule(s) once a day. Starting from day 2 of treatment: one single capsule (plus one of placebo to guarantee the blinding) containing 60 mg raloxifene was administered in Group 1, and 2 capsules 60 mg each for a total of 120 mg in Group 2.

Intervention Type: DRUG

Placebo

Placebo was administered orally once a day as 2 capsules (for maintaining the blinding design)

Intervention Type: OTHER

Other Intervention Names

control

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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dompé Farmaceutici S.p.A

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francesco Sergio, MD, PhD

Role: STUDY_DIRECTOR

Dompé Farmaceutici

Locations

CHU Amiens

Amiens, , France

Clinique de l'infirmerie protestante de Lyon

Caluire-et-Cuire, , France

CH Emile Roux le Puy en Velay

Le Puy-en-Velay, , France

Centre Hospitalier de Troyes

Troyes, , France

Humanitas Gavazzeni

Bergamo, , Italy

Ospedale San Salvatore

L’Aquila, , Italy

AO dei Colli (Ospedale Monaldi)

Napoli, , Italy

INMI Lazzaro Spallanzani

Roma, , Italy

Istituto Clinico Humanitas

Rozzano, , Italy

A.O.U. Città della Salute e della Scienza

Torino, , Italy

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Countries

France; Italy; Spain

References

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.

Reference Type: DERIVED

PMID: 35582123 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-003936-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RLX0120

Identifier Type: -

Identifier Source: org_study_id