NCT04432298

Study of the Efficacy and Safety of Intravenous Pamrevlumab, in Hospitalized Participants With Acute COVID-19 Disease

Terminated Phase 2 Results posted Last updated 18 July 2022

What this trial tests

Phase 2 trial testing Pamrevlumab in COVID-19 in 22 participants. Terminated before completion.

Timeline

20 June 2020

Primary endpoint
22 March 2021

22 March 2021

Quick facts

Lead sponsor	Kyntra Bio
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	22
Start date	20 June 2020
Primary completion	22 March 2021
Estimated completion	22 March 2021
Sites	4 locations across United States

Drugs / interventions tested

• Pamrevlumab — full drug profile →
• Placebo

Conditions studied

• COVID-19 — all drugs for COVID-19 →

Sponsor

Kyntra Bio — full company profile →

Who can join

Adults 40 to 85, any sex, with COVID-19. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Alive Who Never Received Mechanical Ventilation and/or Extracorporeal Membrane Oxygenation (ECMO) at Day 28 Primary · Day 28

Group	Value	95% CI
Pamrevlumab	8
Placebo	9

Number of Participants Alive, Discharged Home, and Not on Supplemental Oxygen at Day 28 Secondary · Day 28

Group	Value	95% CI
Pamrevlumab	6
Placebo	7

Number of Participants Alive Who Never Received Mechanical Ventilation and/or ECMO at Day 14 Secondary · Day 14

Group	Value	95% CI
Pamrevlumab	8
Placebo	9

Time to Recovery as Based on a Modified 8-Point Ordinal Scale Secondary · Day 28

Recovery was defined as the first day on which the participant satisfied 1 of the following 3 categories from the 8-point ordinal scale: (1) hospitalized, not requiring supplemental oxygen; (2) Not hospitalized (discharged), but with limitation on activities and/or requiring home supplemental oxygen; (3) Not hospitalized (discharged), with no limitations on activities and not requiring supplemental oxygen).

Group	Value	95% CI
Pamrevlumab	11	± 10
Placebo	11	± 12

Days in Intensive Care Unit/Critical Care Unit (ICU/CCU) (Either on or Off Mechanical Ventilation and/or ECMO) Secondary · up to Day 28

Days in ICU/CCU was calculated as Event end date/time - Event start data/time + 1. Participants who died in ICU/CCU before Day 28, days in ICU/CCU is calculated up to the death date. Days in ICU/CCU were censored after Day 28.

Group	Value	95% CI
Pamrevlumab	16	± 14
Placebo	12	± 17

Days on Mechanical Ventilation and/or ECMO Secondary · up to Day 28

Days on Mechanical Ventilation and/or ECMO was calculated as Event end date/time - Event start data/time. Participants who died on MV/ECMO before Day 28, days on MV/ECMO is calculated up to the death date. Days on MV/ECMO are censored after Day 28.

Group	Value	95% CI
Pamrevlumab	20.5	± 0.0
Placebo	8.7	± 11.1

Time to Mechanical Ventilation/ECMO or All-cause Mortality Secondary · up to Day 28

Time (number of days) from randomization to mechanical ventilation/ECMO or all-cause mortality by Day 28. Participants without the event are not included in the calculation.

Group	Value	95% CI
Pamrevlumab	14	± 11
Placebo	14	± 1

Number of Participants With All-cause Mortality Secondary · up to Day 28

Group	Value	95% CI
Pamrevlumab	2
Placebo	1

Time to Death From Any Cause Secondary · up to Day 28

Time (number of days) from randomization to death from any cause by Day 28. Participants without the event are not included in the calculation.

Group	Value	95% CI
Pamrevlumab	17	± 15
Placebo	13	± NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to Day 28. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pamrevlumab

Serious: 5/9 (56%)

Deaths: 3/11

Placebo

Serious: 2/11 (18%)

Deaths: 2/11

Serious adverse events (8 terms)

Reaction	System	Pamrevlumab	Placebo
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	—	—
Angina pectoris	Cardiac disorders	—	—
Diabetic ketoacidosis	Metabolism and nutrition disorders	—	—
Metabolic acidosis	Metabolism and nutrition disorders	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—
Shock	Vascular disorders	—	—
Peripheral artery thrombosis	Vascular disorders	—	—
Peripheral ischaemia	Vascular disorders	—	—

Other adverse events (48 terms — click to expand)

Reaction	System	Pamrevlumab	Placebo
Leukocytosis	Blood and lymphatic system disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Platelet count decreased	Investigations	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—
Polycythaemia	Blood and lymphatic system disorders	—	—
Bradycardia	Cardiac disorders	—	—
Supraventricular tachycardia	Cardiac disorders	—	—
Adrenal mass	Endocrine disorders	—	—
Vision blurred	Eye disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Rectal haemorrhage	Gastrointestinal disorders	—	—
Oedema	General disorders	—	—
Oedema peripheral	General disorders	—	—
Hyperbilirubinaemia	Hepatobiliary disorders	—	—
Pneumonia	Infections and infestations	—	—
Clostridium difficile infection	Infections and infestations	—	—
Septic shock	Infections and infestations	—	—
Urinary tract infection	Infections and infestations	—	—
Transaminases increased	Investigations	—	—
Blood glucose increased	Investigations	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—
Hyperkalaemia	Metabolism and nutrition disorders	—	—
Hypernatraemia	Metabolism and nutrition disorders	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—
Hypophosphataemia	Metabolism and nutrition disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	—	—
Dizziness	Nervous system disorders	—	—
Sciatica	Nervous system disorders	—	—
Anxiety	Psychiatric disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	—	—
Atelectasis	Respiratory, thoracic and mediastinal disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Hypoxia	Respiratory, thoracic and mediastinal disorders	—	—
Pneumomediastinum	Respiratory, thoracic and mediastinal disorders	—	—
Pneumothorax	Respiratory, thoracic and mediastinal disorders	—	—

Most-reported serious reactions: Acute respiratory distress syndrome, Angina pectoris, Diabetic ketoacidosis, Metabolic acidosis, Respiratory failure, Shock, Peripheral artery thrombosis, Peripheral ischaemia.

Data from ClinicalTrials.gov NCT04432298 adverse events section.

Sponsor's own description

This study evaluates the efficacy and safety of intravenous (IV) infusions of pamrevlumab when compared with placebo in participants who are hospitalized with acute COVID-19 disease.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. An update to monoclonal antibody as therapeutic option against COVID-19.
   Deb P, Molla MMA, Saif-Ur-Rahman KM. · · 2021 · cited 91× · PMID 33585808 · DOI 10.1016/j.bsheal.2021.02.001
2. Pulmonary fibrosis from molecular mechanisms to therapeutic interventions: lessons from post-COVID-19 patients.
   Giacomelli C, Piccarducci R, Marchetti L, Romei C, et al · · 2021 · cited 48× · PMID 34687672 · DOI 10.1016/j.bcp.2021.114812
3. Recent updates in the clinical trials of therapeutic monoclonal antibodies targeting cytokine storm for the management of COVID-19.
   Patel S, Saxena B, Mehta P. · · 2021 · cited 39× · PMID 33553708 · DOI 10.1016/j.heliyon.2021.e06158
4. Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants.
   Strohl WR, Ku Z, An Z, Carroll SF, et al · · 2022 · cited 31× · PMID 35476216 · DOI 10.1007/s40259-022-00529-7
5. Communication Between Cardiomyocytes and Fibroblasts During Cardiac Ischemia/Reperfusion and Remodeling: Roles of TGF-β, CTGF, the Renin Angiotensin Axis, and Non-coding RNA Molecules.
   Flores-Vergara R, Olmedo I, Aránguiz P, Riquelme JA, et al · · 2021 · cited 24× · PMID 34539441 · DOI 10.3389/fphys.2021.716721
6. Humoral immune mechanisms involved in protective and pathological immunity during COVID-19.
   Widjaja G, Turki Jalil A, Sulaiman Rahman H, Abdelbasset WK, et al · · 2021 · cited 24× · PMID 34229864 · DOI 10.1016/j.humimm.2021.06.011
7. Recent advances in antibody-based immunotherapy strategies for COVID-19.
   Esmaeilzadeh A, Rostami S, Yeganeh PM, Tahmasebi S, et al · · 2021 · cited 24× · PMID 34160093 · DOI 10.1002/jcb.30017
8. An update to "novel therapeutic approaches for treatment of COVID-19".
   Hossein-Khannazer N, Shokoohian B, Shpichka A, Aghdaei HA, et al · · 2021 · cited 21× · PMID 33392632 · DOI 10.1007/s00109-020-02027-1