Clinical trial NCT04794803: Reparixin in COVID-19 Pneumonia - Efficacy and Safety
Official title: Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients With COVID-19 Pneumonia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Severe Pneumonia
Keywords: COVID-19
Lead sponsor: Dompé Farmaceutici S.p.A
Sponsor class: INDUSTRY
First posted: 2021-03-12
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: * Phase 2 Study Objectives: efficacy and safety of of Reparixin treatment as compared to the control arm in adult patients with severe COVID-19 pneumonia
* Phase 3 Study Objectives: efficacy and safety of Reparixin treatment as compared to the control arm in adult patients with moderate or severe COVID-19 pneumonia

Detailed description: This clinical trial is an adaptive phase 2/3, randomized, controlled multicenter study on the efficacy and safety of Reparixin in the treatment of hospitalized patients with COVID-19 pneumonia. 48 patients are planned to be enrolled in Phase 2 and an estimated total of 111 patients are planned to be enrolled up to the end of Phase 3, with a randomization 2:1 Reparixin vs Control (Standard of care).

In the phase 2 segment of this study, patients are randomized 2:1 to Reparixin oral tablets 1200 mg (Group 1, active treatment) or standard of care (Group 2, control arm). In case of worsening (e.g. need of ICU and/or mechanical ventilation) after the first 24hrs, patients are offered a rescue medication with no restriction from the sponsor and fully based on their physicians' judgement.

In the phase 3 segment of this study, it is planned that patients are randomized 2:1 to Reparixin or standard of care. The Phase 3 design will be reassessed and decided based on the results of the Phase 2.

Eligibility criteria: Inclusion Criteria:

* Phase 2 Inclusion Criteria:

  1. Age 18 to 90.
  2. Confirmed COVID-19 diagnosis
  3. At least one of the following: # Respiratory distress, RR ≥ 30 breaths/min without oxygen; # Partial arterial oxygen pressure (PaO2) / Fraction of inspiration O2 (FiO2) \>100 \<300mmHg

  (1mmHg = 0.133kPa). 4. Chest imaging confirms lung involvement and inflammation. 5. Inflammatory status as documented by at least one of the following: Lactate dehydrogenase (LDH) \> normal range, C-reactive protein (CRP) ≥ 100mg/L or IL-6 ≥ 40pg/mL, serum ferritin ≥ 900ng/mL, XDP \>20mcg/mL.
* Phase 3 Inclusion Criteria: Same as above; other criteria TBD based on Phase 2 outcomes.

Exclusion Criteria:

• Phase 2/3 Exclusion Criteria:

1. Cannot obtain informed consent.
2. Severe hepatic dysfunction (Child Pugh score ≥ C, or AST\> 5 times the upper limit); Severe renal dysfunction (estimated glomerular filtration rate ≤ 30mL / min / 1.73 m2) or receive continuous renal replacement therapy, hemodialysis, or peritoneal dialysis.
3. Patients with hypersensitivity to ibuprofen or to more than one non steroidal anti-inflammatory drug or to more than one medication belonging to the class of sulfonamides (e.g. sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib; hypersensitivity to sulphanilamide antibiotics alone, e.g. sulfamethoxazole, does not qualify for exclusion)
4. Severe, active bleeding such as hemoptysis, gastrointestinal bleeding, central nervous system bleeding, and nosebleeds within 1 month before enrollment.
5. Pregnant and lactating women and those planning to get pregnant.
6. Participated in other interventional clinical trials with investigational medicinal products, not considered suitable for this study by the researchers.
7. At the time of enrollment, patients not in a clinical condition compatible with the oral administration of the study drug.

Primary outcomes:
measure: Phase 2 - Percentage of Participants With Composite Endpoint of Clinical Events
timeFrame: Up to Day 1
Secondary outcomes:
measure: Phase 2 - Percentage of Patients With Improvement in Clinical Severity Score (as Recommended by WHO for COVID Studies) of at Least Two Points
timeFrame: At day 1, day 2, week 1, day 21(end of treatment, EOT), EOS (end of study, i.e. 7±3 days after EOT)
measure: Phase 2 - Percentage of Improved Subjects in Dyspnea Severity, Assessed by Liker Scale
timeFrame: Baseline, day 1, day 2, week 1, day 21(end of treatment, EOT), 7±3 days after treatment period (end of study, EOS)
measure: Phase 2 - Change From Baseline in Dyspnea Severity, Assessed by VAS Scale
timeFrame: Baseline, day 1, day 2, week 1, day 21(end of treatment, EOT), 7±3 days after treatment period (end of study, EOS)
measure: Changes From Baseline in Body Temperature to Any Post-baseline Timepoints
timeFrame: Baseline, Day 1, Day 2, Week 1, EOT and EOS
measure: Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to PaO2/FiO2
timeFrame: At day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
measure: Phase 2 - Percentage of Subjects Worsened, During Supplemental Oxygen Treatment, From Randomization According to Oxygen Delivery System Classification
timeFrame: day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
measure: Phase 2 - Oxygen Cumulative Duration During the Study
timeFrame: Week 1, EOT, EOS
measure: Phase 2 - Oxygen Cumulative Quantity During the Study
timeFrame: Week 1, EOT and EOS
measure: Phase 2 - Percentage of Subjects Requiring Mechanical Ventilation Use, Overall
timeFrame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
measure: Phase 2 - Cumulative Duration of Mechanical Ventilation Use, Overall
timeFrame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
measure: Phase 2 - Percentage of Subjects With Intensive Care Unit (ICU) Admission Need
timeFrame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
measure: Phase 2 - Cumulative ICU Stay
timeFrame: Day 1, Day 2, Week 1, EOT, EOS
measure: Phase 2 - Lung Damage Extension by Severity and by Timepoint
timeFrame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
measure: Phase 2 - Lung Exudation by Severity and by Timepoint
timeFrame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
measure: Phase 2 - Change From Baseline in Partial Arterial Oxygen Pressure (PaO2)
timeFrame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
measure: Phase 2 - Change From Baseline in Oxygen Saturation (SpO2)
timeFrame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
measure: Phase 2 - Partial Arterial Oxygen Pressure (PaO2) to Fraction of Inspiration O2 (FiO2) Ratio [PaO2/FiO2 Ratio]
timeFrame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
measure: Phase 2 - Change From Baseline in Reactive Protein (CRP)
timeFrame: Baseline, day 1, day 2, week 1, day 21(end of treatment), follow-up (FU) (7±3 days after treatment period)
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina de São Paulo
city: Milan
country: Italy
facility: Ospedale San Paolo
state: Lombardy
city: Milan
country: Italy
facility: Ospedale San Raffaele
state: Lombardy
city: Varese
country: Italy
facility: Ospedale di Varese
state: Lombardy
Study officials:
affiliation: Ospedale San Raffaele
name: Lorenzo Piemonti, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale San Raffaele
name: Alberto Zangrillo, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Landoni G, Piemonti L, Monforte AD, Grossi P, Zangrillo A, Bucci E, Allegretti M, Goisis G, Gavioli EM, Patel N, De Pizzol M, Pasedis G, Mantelli F. A Multicenter Phase 2 Randomized Controlled Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients with COVID-19 Pneumonia. Infect Dis Ther. 2022 Aug;11(4):1559-1574. doi: 10.1007/s40121-022-00644-6. Epub 2022 May 26.