Clazakizumab vs. Placebo - COVID-19 Infection

Phase 2

• Conditions: COVID-19 Infection
• Interventions: Drug: Placebo; Drug: Clazakizumab

• Registration Number: NCT04494724
• Lead Sponsor: The Methodist Hospital Research Institute

Brief Summary

The purpose of this study is to investigate the effectiveness and safety of treatment with clazakizumab compared to a placebo (inactive substance). We are proposing to try this drug to treat coronavirus disease 2019 (COVID-19) infection. Patients with COVID-19 infection have been shown to have increases in certain inflammatory processes. Clazakizumab is an antibody (immune system protein) that blocks certain inflammatory processes. The treatment plan is to attempt to inhibit or block these inflammatory processes in order to try to limit the damage COVID-19 causes to the lungs.

Detailed Description

The purpose of this randomized, double-blind, placebo-controlled trial is to evaluate the safety and efficacy of clazakizumab vs placebo for the prevention of acute respiratory distress syndrome (ARDS) in patients with COVID-19 and pulmonary manifestations. The study will compare clazakizumab to placebo in a randomized, double-blind fashion followed by an open-label dose of clazakizumab if there is no improvement or a worsening of condition occurs after 24-hours or anytime during the first 14 days after the first dose of clazakizumab or placebo. We hypothesize that clazakizumab will be safely tolerated and will reduce the risk of progression of COVID-19 to acute respiratory distress syndrome.

Primary Objective:

• To evaluate the safety and tolerability of clazakizumab vs placebo for the treatment of patients with COVID-19 disease and signs of pulmonary involvement

Sixty adult patients with COVID-19 and signs of pulmonary involvement at Houston Methodist who are not in need of ventilator support at the time of enrollment.

Study Timeline

• Status Verified: 2020-07
• Study Start: 2020-07-13
• Study First Submitted: 2020-07-21
• Study First Submitted QC: 2020-07-30
• Last Update Submitted: 2020-07-30
• Study First Posted: 2020-07-31
• Last Update Posted: 2020-07-31
• Primary Completion: 2020-12-31
• Study Completion: 2021-07-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Age >18 at the time of screening.

2. Participant or legally authorized representative (LAR) must be able to understand and provide informed consent.

3. Hospitalized with coronavirus disease (COVID-19) confirmed by polymerase chain reaction (PCR) assay from any specimen (eg, respiratory, blood, urine, stool, other bodily fluid) within the prior 72 hours.

4. C-reactive protein (CRP) > 3.5 mg/dL

5. Evidence of pulmonary involvement with at least 2 of the following:

   1. oxygen saturation at rest in ambient air with peripheral capillary oxygen saturation (SpO2) ≤ 94%
   2. tachypnea with resting respiration rate > 25 breaths/minute
   3. Partial pressure of oxygen (PaO2)/initial fraction of inspired oxygen (FiO2) ≤ 300 mmHg
   4. Chest imaging (radiograph, CT, or ultrasound) with abnormalities consistent COVID-19 pneumonia

Exclusion Criteria

1. Previous hypersensitivity or allergic reactions to clazakizumab
2. Lactating or pregnant females
3. Patients with latent tuberculosis (TB) and who are not receiving treatment
4. Patients with active TB
5. Patients with known active inflammatory bowel disease, untreated diverticulitis, or gastrointestinal perforation
6. Requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
7. A significantly abnormal general serum screening lab result defined as a white blood cell (WBC) count < 3.0 X 10^3/mL, a hemoglobin (Hgb) < 8.0 g/dL, a platelet count < 50 X 10^3/mL, an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times upper limit normal
8. Participation in another clinical trial investigating COVID-19-aimed agents
9. Presence of any medical or psychosocial condition, which the investigator believes, would hinder adherence to the study requirements.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo - 50 mL 0.9% saline, IV infusion over 30 minutes.
Clazakizumab	Clazakizumab	Clazakizumab - 25mg in 50 milliliters (mL) of 0.9% saline, IV infusion over 30 minutes.

Primary Outcome Measures

Name	Time	Method
Primary Endpoint	24 hours	Proportion of participants who experience treatment-related adverse events (TEAE) ≥ Grade 3 (CTCAE v5.0) during the first 24 hours after infusion of clazakizumab or placebo

Secondary Outcome Measures

Name	Time	Method
Requirement for mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO)	14 days	Proportion of participants who need mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO) after the first dose of clazakizumab or placebo
Time in the hospital	60 days	Number of days in the hospital following the first dose of clazakizumab or placebo
Infusion-related reactions during 24 hours from the time of infusion	24 hours	Proportion of participants who experience infusion-related reactions during the first 24 hours after infusion of clazakizumab or placebo
Patient survival at 28 days	28 days	Proportion of participants alive at day 28 after the first dose of clazakizumab or placebo
Patient survival at 60 days	60 days	Proportion of participants alive at day 60 after the first dose of clazakizumab or placebo
Requirement for open-label clazakizumab	14 days	Proportion of participants who require an open-label dose of clazakizumab
Time in the intensive care unit (ICU)	60 days	Number of days in the ICU following the first dose of clazakizumab or placebo
Time to mechanical ventilation	60 days	Number of days from first dose of clazakizumab or placebo to requiring mechanical ventilation
Clinical status improvement assessed by the World Health Organization (WHO) Clinical Progression Scale at day 14	14 days	Difference in WHO Clinical Progression Scale between clazakizumab and placebo
Change in Radiologic Assessment of Lung Edema (RALE) at day 14	14 days	Difference in mean or median change in radiologic assessment of lung edema (RALE) score at day 14 from baseline between clazakizumab or placebo
Clinical status improvement assessed by World Health Organization (WHO) Clinical Progression Scale at day 28	28 days	Difference in WHO Clinical Progression Scale between clazakizumab and placebo
Change in Radiologic Assessment of Lung Edema (RALE) at day 28	28 days	Difference in mean or median change in radiologic assessment of lung edema (RALE) score at day 28 from baseline between clazakizumab or placebo

Trial Locations

Locations (1)

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States