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Trial record 1 of 1 for:    APL-9
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A Study of APL-9 in Adults With Mild to Moderate ARDS Due to COVID-19

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ClinicalTrials.gov Identifier: NCT04402060
Recruitment Status : Completed
First Posted : May 26, 2020
Results First Posted : March 23, 2022
Last Update Posted : March 23, 2022
Sponsor:
Information provided by (Responsible Party):
Apellis Pharmaceuticals, Inc.

Brief Summary:

The purpose of this study is to evaluate the safety and effectiveness of APL-9 in adults with mild to moderate ARDS (acute respiratory distress syndrome) caused by COVID-19 who are hospitalized and require supplemental oxygen therapy with or without mechanical ventilation.

It is thought that COVID-19 activates the complement system, part of the immune system that responds to infection or tissue damage, and increases inflammation in the lungs. APL-9 has been designed to inhibit or block activation of part of the complement pathway, and potentially reduce inflammation in the lungs.

Part 1 of the study is open-label to evaluate safety; all participants will receive APL-9 plus standard of care. Part 2 of the study is double-blind, randomized; participants will receive either APL-9 or the vehicle-control plus standard of care.


Condition or disease Intervention/treatment Phase
COVID Covid-19 Coronavirus Coronavirus Infection Severe Acute Respiratory Syndrome Severe Acute Respiratory Syndrome Coronavirus 2 Sars-CoV2 Ards Acute Respiratory Distress Syndrome Drug: APL-9 Other: Vehicle Control Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blinded, Vehicle-Controlled, Multicenter, Parallel-Group Study of APL-9 in Mild to Moderate Acute Respiratory Distress Syndrome Due to COVID-19
Actual Study Start Date : May 28, 2020
Actual Primary Completion Date : February 13, 2021
Actual Study Completion Date : February 13, 2021


Arm Intervention/treatment
Experimental: 180 mg APL-9 IV plus SOC Drug: APL-9
Complement (C3) Inhibitor

Placebo Comparator: Isotonic saline plus SOC Other: Vehicle Control
Normal saline of equal volume to active arm




Primary Outcome Measures :
  1. Number of Subjects Who Experienced Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [ Time Frame: From the first dose of study drug and up to 30 (+7) days after the last dose of study drug. Part 1: Day 1 up to Day 44; Part 2: Day 1 up to Day 58 ]
    TEAEs were defined as those adverse events that developed or worsened in severity after initiation of the first dose of study drug and up to 30 (+7) days beyond the last dose of study drug. A serious TEAE was any TEAE or suspected adverse reaction that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes: death; is life threatening; inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; or a congenital anomaly/birth defect.


Secondary Outcome Measures :
  1. Hospital Length of Stay [ Time Frame: Part 2: Day 1 up to Day 58 ]
    Hospital length of stay was defined as randomization date to hospital discharge. For subjects with death of any cause or withdrawal of study participation, hospital length of stay was imputed with the longest hospital length of stay observed in the study. Median hospital length of stay was estimated using the Kaplan-Meier method.

  2. Overall Survival [ Time Frame: Part 2: Day 1 up to Day 58 (until the safety follow-up assessment 30 days after last study treatment [+7 days]) ]
    Overall survival was defined as randomization date to death of any cause, censored at the last day known to be alive. Median overall survival was estimated using the Kaplan-Meier method.

  3. Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score Over Time [ Time Frame: Part 2: Baseline (Day 1) and Days 3, 5, 7, 11, 15 and end of treatment (EOT) visit (up to Day 21) ]
    The SOFA score is an aggregate score based on objective measures of 6 organ systems: respiratory, coagulation, hepatic, cardiovascular, neurologic, and renal. The minimum value is 0 and maximum value is 24. Higher scores indicate worse outcomes. A subject with a SOFA score of zero was defined as being free of organ failure.

  4. Total Duration of Mechanical Ventilation [ Time Frame: Part 2: Day 1 up to Day 58 ]
    Total duration of mechanical ventilation was calculated from the randomization date and was defined as days on mechanical ventilation during the study participation. For subjects with death of any cause (or withdrawal of study participation), total duration of mechanical ventilation was imputed with the longest duration observed in the study. Any subject who was not on mechanical ventilation at the randomization date was excluded. Median total duration of mechanical ventilation was estimated using the Kaplan-Meier method.

  5. Total Duration of Oxygen Therapy [ Time Frame: Part 2: Day 1 up to Day 58 ]
    Total duration of oxygen therapy was calculated from randomization date and was defined as days on mechanical ventilation or supplemental oxygen during the study participation. For subjects with death of any cause (or withdrawal of study participation), total duration of oxygen therapy was imputed with the longest duration observed in the study. Any subject who was not on mechanical ventilation or supplemental oxygen at the randomization date was excluded. Median total duration of oxygen therapy was estimated using the Kaplan-Meier method.

  6. Serum Concentration of APL-9 Over Time [ Time Frame: Part 1: Day 1 (pre- and post-dose) and Days 3, 5 and 7 (including EOT visit); Part 2: Day 1 (pre- and post-dose) and Days 3, 5, 7, 11, 15 and EOT visit (up to Day 21) ]
    To evaluate pharmacokinetics (PK), blood samples were collected at pre-specified timepoints and serum concentrations of APL-9 were determined. Blood was collected 3 times on Day 1: prior to the initial infusion, as soon as possible following the initial infusion (within 5-10 minutes) prior to the continuous infusion, and at 2 hours after the beginning of the continuous infusion. Blood was then collected once daily between 1-2 hours after the first dose on Days 3, 5, 7, 11 (if treatment was ongoing), Day 15 (if treatment was ongoing) and at the EOT visit.

  7. Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3 and C4 [ Time Frame: Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) ]
    To evaluate pharmacodynamic (PD) parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarkers C3 and C4.

  8. Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Components C3a, C4a, C5a and Terminal Complement Complex (TCC) [ Time Frame: Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) ]
    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarkers C3a, C4a, C5a and TCC.

  9. Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Complement Bb [ Time Frame: Part 1: Baseline (Day 1) and EOT visit (up to Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) ]
    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarker Bb, a marker of alternative pathway activation.

  10. Change From Baseline at EOT Visit in Biomarkers of Complement Activation: Alternative Complement Pathway Hemolytic Activity (AH50) [ Time Frame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) ]
    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for complement biomarker AH50.

  11. Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Reticulocytes [ Time Frame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) ]
    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker reticulocytes. Percentage (%) of reticulocytes was calculated as (Number of Reticulocytes / Number of Red Blood Cells) X 100.

  12. Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Schistocytes [ Time Frame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) ]
    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker schistocytes.

  13. Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Lactate Dehydrogenase [ Time Frame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) ]
    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarker lactate dehydrogenase.

  14. Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: D-Dimer and Ferritin [ Time Frame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) ]
    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarkers D-dimer and ferritin.

  15. Change From Baseline at EOT Visit in Biomarkers of Coagulopathy: Haptoglobin and Fibrinogen [ Time Frame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) ]
    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the coagulation biomarkers haptoglobin and fibrinogen.

  16. Change From Baseline at EOT Visit in Biomarkers of Inflammation: C-reactive Protein (CRP) [ Time Frame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) ]
    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the inflammatory cytokine CRP.

  17. Change From Baseline at EOT Visit in Biomarkers of Inflammation: Tumor Necrosis Factor Alpha (TNFα), Interleukin-1-beta (IL-1β) and Interleukin-6 (IL-6) [ Time Frame: Part 1: Baseline (Day 1) and EOT visit (Day 7); Part 2: Baseline (Day 1) and EOT visit (up to Day 21) ]
    To evaluate PD parameters, blood samples were collected at pre-specified timepoints. Results are presented for change from baseline to EOT visit for the inflammatory cytokines TNFα, IL-1β and IL-6.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Be at least 18 years of age at time of informed consent
  • Diagnosis of active SARS CoV 2 infection using viral RNA or viral antigen within 7 days of screening
  • Respiratory failure requiring oxygen supplementation or either invasive or noninvasive mechanical ventilation with PaO2/FiO2 ratio >100 mm Hg. Respiratory failure cannot be fully explained by cardiac failure or fluid overload.

Exclusion Criteria:

  • Treatment with immune checkpoint inhibitors, or other immunomodulators within 3 months prior to study enrollment (however, treatment with convalescent plasma, steroids, IL-6 inhibitors, and antiviral agents is NOT excluded)
  • Active bacterial, fungal, or parasitic infection
  • History of neuromuscular degenerative disease (eg, amyotrophic lateral sclerosis, Duchenne muscular dystrophy, or multiple sclerosis)
  • Current participation in an interventional clincial trial
  • Subjects who have, at screening, been on mechanical ventilation for >7 days Have evidence of kidney and liver failure at screening
  • Have a hereditary complement deficiency
  • Pregnancy or breastfeeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04402060


Locations
Show Show 24 study locations
Sponsors and Collaborators
Apellis Pharmaceuticals, Inc.
  Study Documents (Full-Text)

Documents provided by Apellis Pharmaceuticals, Inc.:
Study Protocol  [PDF] November 9, 2020
Statistical Analysis Plan  [PDF] May 11, 2021

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Responsible Party: Apellis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04402060    
Other Study ID Numbers: APL9-COV-201
First Posted: May 26, 2020    Key Record Dates
Results First Posted: March 23, 2022
Last Update Posted: March 23, 2022
Last Verified: March 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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COVID-19
Coronavirus Infections
Severe Acute Respiratory Syndrome
Respiratory Distress Syndrome
Respiratory Distress Syndrome, Newborn
Acute Lung Injury
Syndrome
Disease
Pathologic Processes
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury