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

NCT05172050 | Completed Phase 2 Results

• 2 other identifiers: RLX01202020-003936-25
• Study Type: interventional
• Target: 61
• Locations: 3 countries
• Sites: 11

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

Conditions

SARS CoV 2 Infection

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Undetectable SARS-CoV-2 at PCR at Day 7 After Randomization in the FAS

  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" .

  At Day 7

• Number of Participants Not Requiring Oxygen Therapy and/or Mechanical Ventilation at Day 14 After Randomization in the FAS

  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).

  At Day 14

Secondary Outcomes (9)

• 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 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 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 Hospitalized Participants Who at the Beginning of the Study Were at Domicile Isolation After Randomization in the FAS

  At days 7, 14, 28

Study Arms (3)

Group 1: Raloxifene 60 mg

EXPERIMENTAL

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.

Drug: Raloxifene

Group 2: Raloxifene 120 mg

EXPERIMENTAL

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.

Drug: Raloxifene

Group 3: Placebo.

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

Raloxifene 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 1: Raloxifene 60 mg; Group 2: Raloxifene 120 mg

Placebo OTHER

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

Also known as: control

Group 3: Placebo.

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• A male sexual partner who agrees to use a male condom with spermicide
• 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.

You may not qualify if:

• 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
• Diseases:
• 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;
• signs or symptoms of endometrial cancer
• Autoimmune diseases receiving therapy at the time of randomization
• Risk of venous thrombosis or any condition/disease that could bring to an extended period of immobilization
• 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

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead

Study Sites (11)

CHU Amiens

Amiens, France

Location

Clinique de l'infirmerie protestante de Lyon

Caluire-et-Cuire, France

Location

CH Emile Roux le Puy en Velay

Le Puy-en-Velay, France

Location

Centre Hospitalier de Troyes

Troyes, France

Location

Humanitas Gavazzeni

Bergamo, Italy

Location

Ospedale San Salvatore

L’Aquila, Italy

Location

AO dei Colli (Ospedale Monaldi)

Napoli, Italy

Location

INMI Lazzaro Spallanzani

Roma, Italy

Location

Istituto Clinico Humanitas

Rozzano, Italy

Location

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

Torino, Italy

Location

Hospital Universitario Virgen de la Victoria

Málaga, Spain

Location

Related Publications (1)

• 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.

  PMID: 35582123 DERIVED

MeSH Terms

Conditions

COVID-19; Pneumonia

Interventions

Raloxifene Hydrochloride

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Tamoxifen; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Clinical Development & Operations
• Organization: Dompé Farmaceutici SpA

clinical.trials@dompe.com

+39 02 583831

Study Officials

• Francesco Sergio, MD, PhD

  Dompé Farmaceutici

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Appearance, including packaging and labelling, of the investigational medicinal product (IMP, capsules, packaging) will not allow to recognize actual treatment (either raloxifene or placebo).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 23, 2021
• First Posted: December 29, 2021
• Study Start: January 22, 2021
• Primary Completion: June 12, 2021
• Study Completion: June 12, 2021
• Last Updated: December 26, 2023
• Results First Posted: December 14, 2023

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4); IT (6); ES (1)