Trial Outcomes & Findings for Double Blind, Placebo Controlled Study of Safety and Efficacy of Leronlimab in Patients With "Long" COVID-19 (NCT NCT04678830)

Last Updated: 2024-04-11

Results Overview

Changes in common COVID-19-related symptoms were evaluated daily by the patient using a patient diary between start and end of treatment. The diary is shown in Appendix 17.1 in the protocol and covers patient-reported changes for symptoms (ranked as none = 0, mild = 1, moderate = 2 or severe = 3) of cough, sore throat, stuffy or runny nose, difficulty breathing, feeling tightness in chest, feeling fast heartbeat, fatigue, exertional malaise, muscle aches and cramps, muscle weakness, joint pain and swelling, shivering and chills, feeling hot or feverish, difficulty concentrating, insomnia, headache, dizziness, anxiety, tingling or numbness, nausea, vomiting, diarrhea, sense of smell, sense of taste. Maximum score could be 70 (22 parameters with scores up to 3, two parameters with scores up to 2), lowest score could be 0. A negative value shows improvement in symptoms. The lower the value, the greater the improvement (i.e., a score of -16 is greater improvement than a score of -8).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

56 participants

Primary outcome timeframe

Changes in COVID-19 related symptoms from baseline (start of treatment) and day 56 (end of treatment)

Results posted on

2024-04-11

Participant Flow

Fifty six (56) subjects were enrolled in the study with 28 subjects in each treatment arm. All patients were enrolled under protocol version 3.0 (effective date 25-Feb-2021). The study was performed between 01 March 2021 and 01 July 2021.

Participant milestones

Participant milestones
Measure	Placebo Syringes containing normal saline for injection were prepared by an unblinded pharmacist at the clinical sites for use as the placebo. Placebos: Placebos	700mg Leronlimab Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections Leronlimab (700mg): Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)
Overall Study STARTED	28	28
Overall Study COMPLETED	26	27
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Syringes containing normal saline for injection were prepared by an unblinded pharmacist at the clinical sites for use as the placebo. Placebos: Placebos	700mg Leronlimab Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections Leronlimab (700mg): Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)
Overall Study Lack of Efficacy	2	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Double Blind, Placebo Controlled Study of Safety and Efficacy of Leronlimab in Patients With "Long" COVID-19

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	700mg Leronlimab n=28 Participants Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections Leronlimab (700mg): Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)	Placebo n=28 Participants Syringes containing normal saline for injection were prepared by an unblinded pharmacist at the clinical sites for use as the placebo. Placebos: Placebos	Total n=56 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	26 Participants n=5 Participants	23 Participants n=7 Participants	49 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Age, Continuous	45.5 years STANDARD_DEVIATION 12.8 • n=5 Participants	51.6 years STANDARD_DEVIATION 13.2 • n=7 Participants	48.6 years STANDARD_DEVIATION 13.24 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants n=5 Participants	27 Participants n=7 Participants	52 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants	27 Participants n=7 Participants	55 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	28 participants n=5 Participants	28 participants n=7 Participants	56 participants n=5 Participants
Baseline COVID-19 Related Symptom Score	32.5 units on a scale STANDARD_DEVIATION 9.96 • n=5 Participants	26.9 units on a scale STANDARD_DEVIATION 10.19 • n=7 Participants	29.4 units on a scale STANDARD_DEVIATION 10.64 • n=5 Participants

PRIMARY outcome

Timeframe: Changes in COVID-19 related symptoms from baseline (start of treatment) and day 56 (end of treatment)

Population: The Modified Intent-to-Treat (mITT) population was defined as the set of subjects who received at least one dose of leronlimab (PRO 140) or placebo. This population was to be used for the analysis of efficacy parameters or measurements. Fifty six (56) patients received at least one dose of leronlimab or placebo.

Outcome measures

Outcome measures
Measure	700mg Leronlimab n=28 Participants Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections Leronlimab (700mg): Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)	Placebo n=28 Participants Syringes containing normal saline for injection were prepared by an unblinded pharmacist at the clinical sites for use as the placebo. Placebos: Placebos
Changes From Baseline in Daily COVID-19-related Symptom Severity Score Through Day 56.	-16.3 units on a scale Standard Deviation 13.14	-8.1 units on a scale Standard Deviation 12.27

SECONDARY outcome

Timeframe: Duration of symptoms from baseline (day 0, start of treatment) and day 56 (end of treatment)

Population: mITT

Number of days when any symptoms scored as moderate or severe at baseline (Day 0) are still scored as moderate or severe through day 56 (end of treatment) or symptoms scored as mild or absent at baseline are scored as mild or worse at day 56 (end of treatment).

Outcome measures

Outcome measures
Measure	700mg Leronlimab n=28 Participants Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections Leronlimab (700mg): Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)	Placebo n=28 Participants Syringes containing normal saline for injection were prepared by an unblinded pharmacist at the clinical sites for use as the placebo. Placebos: Placebos
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of cough	14.9 days Standard Deviation 18.8	7.8 days Standard Deviation 12.8
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of sore throat	10.6 days Standard Deviation 15.7	9.4 days Standard Deviation 13.4
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of Stuff/Runny Nose	19.3 days Standard Deviation 23.0	20.7 days Standard Deviation 20.9
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of shortness of breath	11.5 days Standard Deviation 17.4	13.9 days Standard Deviation 17.4
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of tightness of chest	10.3 days Standard Deviation 14.8	12.3 days Standard Deviation 17.1
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of fast heartbeat	14.8 days Standard Deviation 18.7	16.0 days Standard Deviation 15.6
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of fatigue	6.5 days Standard Deviation 14.0	10.6 days Standard Deviation 18.4
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of exertional malaise	12.7 days Standard Deviation 18.8	10.6 days Standard Deviation 15.3
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) muscle aches / cramps	16.5 days Standard Deviation 19.6	17.7 days Standard Deviation 16.6
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of Muscle Weakness	17.1 days Standard Deviation 19.4	20.8 days Standard Deviation 17.9
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) joint pain/swelling	15.9 days Standard Deviation 16.7	18.3 days Standard Deviation 18.6
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of chills or shivering	6.6 days Standard Deviation 11.1	3.9 days Standard Deviation 7.7
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of feeling hot or feverish	10.5 days Standard Deviation 13.6	9.9 days Standard Deviation 16.2
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of difficulty in concentration	15.6 days Standard Deviation 20.3	11.8 days Standard Deviation 17.7
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of sleep disturbance	13.3 days Standard Deviation 17.2	14.4 days Standard Deviation 17.5
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of headache	16.0 days Standard Deviation 16.6	17.8 days Standard Deviation 18.0
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of dizziness	11.8 days Standard Deviation 17.6	16.9 days Standard Deviation 18.6
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of anxiety	16.8 days Standard Deviation 22.3	15.1 days Standard Deviation 17.4
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of tingling or numbness	14.0 days Standard Deviation 19.3	18.3 days Standard Deviation 19.4
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of nausea	6.8 days Standard Deviation 9.8	8.5 days Standard Deviation 12.5
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of vomiting	0.3 days Standard Deviation 0.7	0.6 days Standard Deviation 1.6
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of diarrhea	8.5 days Standard Deviation 13.7	7.1 days Standard Deviation 9.5
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) of change to sense of smell	16.8 days Standard Deviation 21.2	8.5 days Standard Deviation 15.5
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Duration (days) in change of sense of taste	13.5 days Standard Deviation 18.3	8.6 days Standard Deviation 17.0

SECONDARY outcome

Timeframe: Between start of treatment (day0) and day 56 (end of treatment)

Population: mITT

Symptom-free days are defined as number of days when any symptoms scored as mild, moderate or severe at baseline are scored as absent (or none) through Day 56 (end of treatment) using a self-assessment diary.

Outcome measures

Outcome measures
Measure	700mg Leronlimab n=28 Participants Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections Leronlimab (700mg): Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)	Placebo n=28 Participants Syringes containing normal saline for injection were prepared by an unblinded pharmacist at the clinical sites for use as the placebo. Placebos: Placebos
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free of chills or shivering	12.6 Days Standard Deviation 19.4	16.6 Days Standard Deviation 21.6
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free from anxiety	5.1 Days Standard Deviation 11.0	12.4 Days Standard Deviation 16.4
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free from tingling or numbness	16.5 Days Standard Deviation 20.1	9.0 Days Standard Deviation 15.8
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free of cough	16.8 Days Standard Deviation 19.4	11.3 Days Standard Deviation 17.1
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free of sore throat	4.9 Days Standard Deviation 9.8	11.5 Days Standard Deviation 18.5
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free of stuffy or runny nose	8.7 Days Standard Deviation 13.2	12.8 Days Standard Deviation 17.7
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free of shortness of breath	8.2 Days Standard Deviation 12.0	15.0 Days Standard Deviation 17.0
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free of tightness of chest	10.3 Days Standard Deviation 16.1	13.4 Days Standard Deviation 19.0
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free of fast heartbeat	12.8 Days Standard Deviation 16.5	16.4 Days Standard Deviation 18.8
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free of fatigue	3.9 Days Standard Deviation 7.5	5.4 Days Standard Deviation 10.9
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free of exertional malaise	7.2 Days Standard Deviation 10.5	11.1 Days Standard Deviation 15.0
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free of muscle aches and cramps	9.1 Days Standard Deviation 13.7	14.2 Days Standard Deviation 15.5
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free of muscle weakness	9.5 Days Standard Deviation 14.7	12.0 Days Standard Deviation 16.1
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free of joint pain/swelling	10.5 Days Standard Deviation 17.8	5.1 Days Standard Deviation 12.7
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free of being hot or feverish	14.8 Days Standard Deviation 20.4	14.5 Days Standard Deviation 18.2
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free from difficulty concentrating	4.6 Days Standard Deviation 9.1	7.4 Days Standard Deviation 13.3
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free from sleep disturbance	10.3 Days Standard Deviation 12.1	13.6 Days Standard Deviation 15.7
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free from headache	15.4 Days Standard Deviation 16.2	12.5 Days Standard Deviation 16.4
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free from dizziness	11.0 Days Standard Deviation 18.5	9.9 Days Standard Deviation 15.3
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free from nausea	14.0 Days Standard Deviation 19.8	13.9 Days Standard Deviation 18.1
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free from diarrhea	8.3 Days Standard Deviation 15.0	13.6 Days Standard Deviation 18.3
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free from change in sense of smell	7.8 Days Standard Deviation 14.2	6.9 Days Standard Deviation 15.3
Number of Days Free of Symptoms Associated With COVID-19 That Were Present at the Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary. Days free from change in sense of taste	8.8 Days Standard Deviation 16.3	8.0 Days Standard Deviation 16.9

SECONDARY outcome

Timeframe: Between start of treatment (day0) and day 56 (end of treatment)

Population: mITT

Progression or worsening of symptoms is defined as number of days when any symptoms scored as 2 at baseline scored as 3 through day 56 or 1 at baseline are scored as 2 or 3 through day 56 or scored 0 at study entry scored as 1, 2 or 3 through day 56. No change in symptoms would give a score of 0, symptom progression would give a positive number, symptom improvement would a negative number. Minimum baseline symptom score for eligibility for the study was 6. Maximum symptom score is 70, therefore if all symptoms progressed to the severest level the change in score would be +64. If all patients had a severe score for all symptoms at baseline and all improved to no symptoms at day 56, the maximum improvement in score would be -70.

Outcome measures

Outcome measures
Measure	700mg Leronlimab n=23 Participants Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections Leronlimab (700mg): Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)	Placebo n=25 Participants Syringes containing normal saline for injection were prepared by an unblinded pharmacist at the clinical sites for use as the placebo. Placebos: Placebos
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Shortness of breath	-0.8 score on a scale Standard Deviation 1.0	-0.6 score on a scale Standard Deviation 0.9
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Tightness of chest	-0.6 score on a scale Standard Deviation 0.9	-0.3 score on a scale Standard Deviation 0.9
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Cough	-0.6 score on a scale Standard Deviation 0.8	-0.4 score on a scale Standard Deviation 0.9
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Sore throat	-0.1 score on a scale Standard Deviation 0.7	-0.2 score on a scale Standard Deviation 0.8
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Stuffy or runny nose	-0.7 score on a scale Standard Deviation 0.8	-0.1 score on a scale Standard Deviation 0.8
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Fast heartbeat	-0.8 score on a scale Standard Deviation 0.8	-0.5 score on a scale Standard Deviation 1.0
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Fatigue	-1.1 score on a scale Standard Deviation 0.9	-1.1 score on a scale Standard Deviation 1.0
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Exertional Malaise	-1.1 score on a scale Standard Deviation 1.1	-0.9 score on a scale Standard Deviation 1.0
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Muscle aches and cramps	-0.9 score on a scale Standard Deviation 0.9	-0.7 score on a scale Standard Deviation 0.9
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Muscle weakness	-0.9 score on a scale Standard Deviation 1.1	-0.5 score on a scale Standard Deviation 0.8
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Joint Pain/swelling	-0.8 score on a scale Standard Deviation 0.7	-0.3 score on a scale Standard Deviation 0.9
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Chills and shivering	-0.6 score on a scale Standard Deviation 0.6	-0.5 score on a scale Standard Deviation 0.8
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Hot or feverish	-0.5 score on a scale Standard Deviation 0.8	-0.6 score on a scale Standard Deviation 1.1
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Difficulty in concentrating	-1.0 score on a scale Standard Deviation 1.0	-1.1 score on a scale Standard Deviation 1.0
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Sleep disturbance	-1.2 score on a scale Standard Deviation 0.9	-1.1 score on a scale Standard Deviation 1.0
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Headache	-1.0 score on a scale Standard Deviation 1.0	-0.7 score on a scale Standard Deviation 1.0
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Dizziness	-0.7 score on a scale Standard Deviation 1.0	-0.4 score on a scale Standard Deviation 0.9
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Anxiety	-0.7 score on a scale Standard Deviation 0.9	-0.8 score on a scale Standard Deviation 0.8
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Tingling or numbness	-0.8 score on a scale Standard Deviation 1.0	-0.3 score on a scale Standard Deviation 0.9
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Nausea	-0.6 score on a scale Standard Deviation 0.9	-0.5 score on a scale Standard Deviation 0.9
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Vomiting	0.0 score on a scale Standard Deviation 0.1	0.0 score on a scale Standard Deviation 0.1
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Diarrhea	-0.0 score on a scale Standard Deviation 0.6	-0.6 score on a scale Standard Deviation 1.0
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Sense of Smell	-0.3 score on a scale Standard Deviation 0.5	-0.2 score on a scale Standard Deviation 0.4
Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline. Sense of taste	-0.3 score on a scale Standard Deviation 0.5	-0.2 score on a scale Standard Deviation 0.4

SECONDARY outcome

Timeframe: Between Baseline (day 0), Visit 4 (day 7), Visit 6 (day 14), Visit 8 (day 21) Visit 10 (day 28), Visit 12 (day 35), Visit 14 (day 42), Visit 16 (Day 56) and Visit 17 (day 56, end of treatment).

Population: mITT

Change from baseline in physical and psychological fatigue measured using the PROMIS® scale. A decrease in the score compared to baseline shows an improvement in the symptom. PROMIS definition - Patient-Reported Outcomes Measurement Information System. The Fatigue Short Form (4a) was used (Section 17.3 Appendix 3 of protocol). Raw fatigue scores range from 4 to 20 and are converted to a T-score metric where the response from the general population is set at 50 with standard deviations at 10; a score of greater than 60 would be one std dev greater than the general population, meaning more fatigue. A link to the fatigue score maps is provided in the hyperlinks section. The minimum fatigue T-score is 33.7 (with a std error of 4.9) and a maximum score of 75.8 (with a std error of 3.9). The higher the score, the more fatigue. A decrease in the fatigue score from baseline to day 28 and day 56 would indicate decrease in fatigue.

Outcome measures

Outcome measures
Measure	700mg Leronlimab n=28 Participants Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections Leronlimab (700mg): Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)	Placebo n=28 Participants Syringes containing normal saline for injection were prepared by an unblinded pharmacist at the clinical sites for use as the placebo. Placebos: Placebos
Change From Baseline in PROMIS® Fatigue Score at Days 7,14, 21, 28, 35, 42 and End of Treatment (Day 56). change from baseline to visit 16 (day 49)	-11.8 Units on a scale Standard Deviation 12.9	-11.0 Units on a scale Standard Deviation 11.5
Change From Baseline in PROMIS® Fatigue Score at Days 7,14, 21, 28, 35, 42 and End of Treatment (Day 56). Baseline score (day 0)	68.4 Units on a scale Standard Deviation 6.5	66.6 Units on a scale Standard Deviation 7.1
Change From Baseline in PROMIS® Fatigue Score at Days 7,14, 21, 28, 35, 42 and End of Treatment (Day 56). Change from baseline to visit 4 (day 7)	-5.3 Units on a scale Standard Deviation 9.9	-6.1 Units on a scale Standard Deviation 8.5
Change From Baseline in PROMIS® Fatigue Score at Days 7,14, 21, 28, 35, 42 and End of Treatment (Day 56). Change from baseline to visit 6 (day 14)	-7.6 Units on a scale Standard Deviation 10.7	-7.6 Units on a scale Standard Deviation 8.5
Change From Baseline in PROMIS® Fatigue Score at Days 7,14, 21, 28, 35, 42 and End of Treatment (Day 56). Change from baseline to visit 8 (day 21)	-8.4 Units on a scale Standard Deviation 14.6	-10.2 Units on a scale Standard Deviation 10.1
Change From Baseline in PROMIS® Fatigue Score at Days 7,14, 21, 28, 35, 42 and End of Treatment (Day 56). Change from baseline to visit 10 (day 28)	-8.8 Units on a scale Standard Deviation 12.1	-7.5 Units on a scale Standard Deviation 10.5
Change From Baseline in PROMIS® Fatigue Score at Days 7,14, 21, 28, 35, 42 and End of Treatment (Day 56). Change from baseline to Visit 12 (day 25)	-11.1 Units on a scale Standard Deviation 13.4	-8.6 Units on a scale Standard Deviation 10.8
Change From Baseline in PROMIS® Fatigue Score at Days 7,14, 21, 28, 35, 42 and End of Treatment (Day 56). Change from baseline to visit 14 (day 42)	-11.0 Units on a scale Standard Deviation 14.0	-8.1 Units on a scale Standard Deviation 11.2
Change From Baseline in PROMIS® Fatigue Score at Days 7,14, 21, 28, 35, 42 and End of Treatment (Day 56). Change from baseline to end of treatment (day 56)	-11.1 Units on a scale Standard Deviation 11.9	-10.2 Units on a scale Standard Deviation 10.8

SECONDARY outcome

Timeframe: Baseline (start of treatment), day 28 and day 56 (end of treatment)

Population: mITT

Change in cognitive function score between baseline, day 28 and day 56 were measured using the PROMIS Cognitive Function Assessment Short Form 4a. Higher scores on the PROMIS Cognitive Function Assessment indicate better perceived cognitive functioning. Answers to 4 questions with scores ranging from 1 (very often - several times a day) to 5 (never) provide raw scores that are then normalized T scores. A T score of 50 is the mean of the general population, with std devs of 10, therefore a score of 40 is one std dev lower than that of the general population. The lowest raw score (4) converts to a T score of 24.99 while the highest raw score (20) converts to a T score of 61.13. A link to the PROMIS scoring maps is provided in the hyperlinks section. An increase in score for cognitive function assessment represents an increase in cognitive function

Outcome measures

Outcome measures
Measure	700mg Leronlimab n=28 Participants Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections Leronlimab (700mg): Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)	Placebo n=28 Participants Syringes containing normal saline for injection were prepared by an unblinded pharmacist at the clinical sites for use as the placebo. Placebos: Placebos
Change From Baseline in PROMIS® Cognitive Function Score at Days 7, 14, 21, 28, 35, 42, 49 and End of Treatment (d56) Baseline (day 0)	29.6 units on a scale Standard Deviation 5.5	34.6 units on a scale Standard Deviation 9.5
Change From Baseline in PROMIS® Cognitive Function Score at Days 7, 14, 21, 28, 35, 42, 49 and End of Treatment (d56) Change from baseline to visit 4 (day 7)	5.1 units on a scale Standard Deviation 8.9	2.7 units on a scale Standard Deviation 8.2
Change From Baseline in PROMIS® Cognitive Function Score at Days 7, 14, 21, 28, 35, 42, 49 and End of Treatment (d56) Change from baseline to visit 6 (day 14)	7.4 units on a scale Standard Deviation 9.6	4.9 units on a scale Standard Deviation 9.5
Change From Baseline in PROMIS® Cognitive Function Score at Days 7, 14, 21, 28, 35, 42, 49 and End of Treatment (d56) Change from baseline to visit 8 (day 21)	7.4 units on a scale Standard Deviation 10.0	4.6 units on a scale Standard Deviation 7.9
Change From Baseline in PROMIS® Cognitive Function Score at Days 7, 14, 21, 28, 35, 42, 49 and End of Treatment (d56) Change from baseline to visit 10 (day 28)	9.0 units on a scale Standard Deviation 8.9	4.1 units on a scale Standard Deviation 8.0
Change From Baseline in PROMIS® Cognitive Function Score at Days 7, 14, 21, 28, 35, 42, 49 and End of Treatment (d56) Change from baseline to visit 12 (day 35)	10.1 units on a scale Standard Deviation 9.4	6.2 units on a scale Standard Deviation 9.1
Change From Baseline in PROMIS® Cognitive Function Score at Days 7, 14, 21, 28, 35, 42, 49 and End of Treatment (d56) Change from baseline to visit 14 (day 42)	10.8 units on a scale Standard Deviation 11.2	6.2 units on a scale Standard Deviation 8.6
Change From Baseline in PROMIS® Cognitive Function Score at Days 7, 14, 21, 28, 35, 42, 49 and End of Treatment (d56) Change from baseline to visit 16 (day 49)	10.3 units on a scale Standard Deviation 10.8	7.4 units on a scale Standard Deviation 9.7
Change From Baseline in PROMIS® Cognitive Function Score at Days 7, 14, 21, 28, 35, 42, 49 and End of Treatment (d56) Change from baseline to end of treatment (day 56)	10.9 units on a scale Standard Deviation 10.8	6.3 units on a scale Standard Deviation 8.8

SECONDARY outcome

Population: mITT

Assessment of change in sleep disturbance between baseline, day 28 and day 56 used the PROMIS® Sleep Disturbance Short Form (see Appendix 5 in Section 17 of the protocol). Four questions are scored between 1 (best score for good quality sleep) and 5 (worst score) such that the lower the score, the better the sleep. Raw scores are converted to a T-score with a mean of 50 and a standard deviation (SD) of 10 for the general population. T-scores of 60 are one SD worse than average (worse quality sleep). By comparison, Sleep Disturbance T-scores of 40 are one SD better than average. The PROMIS Sleep Disturbance scoring manual shows the lowest sleep disturbance score of 4 converting to a T score of 32 with a std error of 5.2, while the highest score of 20 converts to a T score of 73.3 with a std error of 4.6. The change from baseline is based on patients with paired values.

Outcome measures

Outcome measures
Measure	700mg Leronlimab n=28 Participants Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections Leronlimab (700mg): Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)	Placebo n=28 Participants Syringes containing normal saline for injection were prepared by an unblinded pharmacist at the clinical sites for use as the placebo. Placebos: Placebos
Change From Baseline in PROMIS® Sleep Disturbance Score at Days 7,14, 21, 28, 35, 42, 49 and End of Treatment (Day 56). Change from baseline visit 8 (day 21)	-7.7 score on a scale Standard Deviation 10.2	-5.1 score on a scale Standard Deviation 7.1
Change From Baseline in PROMIS® Sleep Disturbance Score at Days 7,14, 21, 28, 35, 42, 49 and End of Treatment (Day 56). Baseline score (day 0)	60.2 score on a scale Standard Deviation 8.0	58.3 score on a scale Standard Deviation 8.5
Change From Baseline in PROMIS® Sleep Disturbance Score at Days 7,14, 21, 28, 35, 42, 49 and End of Treatment (Day 56). Change from baseline to visit 4 (day 7)	-4.1 score on a scale Standard Deviation 8.6	-1.9 score on a scale Standard Deviation 6.2
Change From Baseline in PROMIS® Sleep Disturbance Score at Days 7,14, 21, 28, 35, 42, 49 and End of Treatment (Day 56). Change from baseline to visit 6 (day 14)	-5.3 score on a scale Standard Deviation 9.6	-3.4 score on a scale Standard Deviation 8.0
Change From Baseline in PROMIS® Sleep Disturbance Score at Days 7,14, 21, 28, 35, 42, 49 and End of Treatment (Day 56). Change from baseline to visit 10 (day 28)	-7.2 score on a scale Standard Deviation 8.9	-5.7 score on a scale Standard Deviation 9.2
Change From Baseline in PROMIS® Sleep Disturbance Score at Days 7,14, 21, 28, 35, 42, 49 and End of Treatment (Day 56). Change from baseline to visit 12 (day 35)	-8.3 score on a scale Standard Deviation 10.8	-4.2 score on a scale Standard Deviation 6.5
Change From Baseline in PROMIS® Sleep Disturbance Score at Days 7,14, 21, 28, 35, 42, 49 and End of Treatment (Day 56). Change from baseline to visit 14 (day 42)	-7.7 score on a scale Standard Deviation 10.7	-5.3 score on a scale Standard Deviation 7.9
Change From Baseline in PROMIS® Sleep Disturbance Score at Days 7,14, 21, 28, 35, 42, 49 and End of Treatment (Day 56). Change from baseline to visit 16 (day 49)	-7.6 score on a scale Standard Deviation 9.5	-6.0 score on a scale Standard Deviation 10.4
Change From Baseline in PROMIS® Sleep Disturbance Score at Days 7,14, 21, 28, 35, 42, 49 and End of Treatment (Day 56). Change from baseline to end of treatment (day 56)	-8.3 score on a scale Standard Deviation 9.4	-5.5 score on a scale Standard Deviation 9.4

SECONDARY outcome

Timeframe: Between baseline (start of treatment) and day 56 (end of treatment)

Population: mITT

Number of participants who required hospitalization during the treatment phase.

Outcome measures

Outcome measures
Measure	700mg Leronlimab n=28 Participants Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections Leronlimab (700mg): Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)	Placebo n=28 Participants Syringes containing normal saline for injection were prepared by an unblinded pharmacist at the clinical sites for use as the placebo. Placebos: Placebos
Number of Participants Requiring Hospitalization During the Treatment Phase	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Between baseline (start of treatment) and day 56 (end of treatment)

Population: mITT

Duration (in days) of hospitalization required during treatment phase

Outcome measures

Outcome measures
Measure	700mg Leronlimab n=28 Participants Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections Leronlimab (700mg): Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)	Placebo n=28 Participants Syringes containing normal saline for injection were prepared by an unblinded pharmacist at the clinical sites for use as the placebo. Placebos: Placebos
Duration (Days) of Hospitalization During the Treatment Phase	0 days	0 days

Adverse Events

700mg Leronlimab

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	700mg Leronlimab n=28 participants at risk Each vial of active contains 350mg of leronlimab at a concentration of 175mg/ml (nominal 2mL fill volume) in formulation buffer containing histidine, glycine, sodium chloride, sorbitol, polysorbate 20 and sterile water for injections Leronlimab (700mg): Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)	Placebo n=28 participants at risk Syringes containing normal saline for injection were prepared by an unblinded pharmacist at the clinical sites for use as the placebo. Placebos: Placebos
Nervous system disorders Seizures and seizure disorders	0.00% 0/28 • Adverse event data was collected between start of treatment (baseline, day 0) and 28 days after end of treatment. First dose was administered on Day 0, last dose (dose 8) was administered on day 49, End of Treatment (EOT) was 7 days after last dose (day 56) and follow-up was for the 28 day period after the EOT visit.	3.6% 1/28 • Number of events 1 • Adverse event data was collected between start of treatment (baseline, day 0) and 28 days after end of treatment. First dose was administered on Day 0, last dose (dose 8) was administered on day 49, End of Treatment (EOT) was 7 days after last dose (day 56) and follow-up was for the 28 day period after the EOT visit.

Other adverse events

Additional Information

Bernie Cunningham, PhD

CytoDyn Inc.

Phone: (360) 980-8524

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place