The purpose of this study is to assess the safety and efficacy of leronlimab (PRO 140) administered as weekly subcutaneous injections in subjects experiencing prolonged symptoms (\> 12 weeks) of COVID-19.
This is a Phase 2, two-arm, randomized, double blind, placebo controlled multicenter study to evaluate the safety and efficacy of leronlimab (PRO 140) in patients with prolonged symptoms caused by Coronavirus Disease 2019 (COVID-19). Patients will be randomized to receive weekly doses of 700 mg leronlimab (PRO 140), or placebo. Leronlimab (PRO 140) and placebo will be administered via subcutaneous injection. The study will have three phases: Screening Period, Treatment Period, and Follow-Up Period. Total study duration is 91 days. The study will be conducted at up to 5 centers in the United States and planned number of subjects are 50 subjects. Visit schedule: Visit 1 - Screening assessment Visit 2 - baseline, first dose Visit 3 - no dose, baseline+3 days Visit 4 - second dose, baseline + 7 days Visit 5 - no dose, safety assessment/con med, baseline +10 days Visit 6 - third dose, baselines + 14 days Visit 7 - no dose, safety assessments, baseline + 17 days Visit 8 - fourth dose, baseline +21 days Visit 9 - no dose, safety assessment, baseline + 24 days Visit 10 - fifth dose, baseline + 28 days Visit 11 - no dose, safety assessment, baseline + 31 days Visit 12 - sixth dose, baseline + 35 days Visit 13 - no dose, safety assessment, baseline + 38 days Visit 14 - seventh dose, baseline + 42 days Visit 15 - no dose, safety assessment, baseline + 45 days Visit 16 - eighth and final dose, baseline + 49 days Visit 17 - End of treatment, baseline + 56 days
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
56
Placebos
Leronlimab (PRO) 140 is a humanized IgG4, monoclonal antibody (mAb) to the C-C chemokine receptor type 5 (CCR5)
Arthritis & Rheumatic Disease Specialties
Aventura, Florida, United States
Center for Advanced Research & Education (CARE)
Gainesville, Georgia, United States
Changes From Baseline in Daily COVID-19-related Symptom Severity Score Through Day 56.
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).
Time frame: Changes in COVID-19 related symptoms from baseline (start of treatment) and day 56 (end of treatment)
Duration of COVID-19 Associated Symptoms From Start of Study Treatment (Day 0) Based on Self-assessment Using Daily Symptom Diary.
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).
Time frame: Duration of symptoms from baseline (day 0, start of treatment) and day 56 (end of treatment)
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.
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.
Time frame: Between start of treatment (day0) and day 56 (end of treatment)
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Progression (or Worsening) of COVID-19-associated Symptoms Through Day 56 Compared to Baseline.
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.
Time frame: Between start of treatment (day0) and day 56 (end of treatment)
Change From Baseline in PROMIS® Fatigue Score at Days 7,14, 21, 28, 35, 42 and End of Treatment (Day 56).
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.
Time frame: 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).
Change From Baseline in PROMIS® Cognitive Function Score at Days 7, 14, 21, 28, 35, 42, 49 and End of Treatment (d56)
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
Time frame: Baseline (start of treatment), day 28 and day 56 (end of treatment)
Change From Baseline in PROMIS® Sleep Disturbance Score at Days 7,14, 21, 28, 35, 42, 49 and End of Treatment (Day 56).
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.
Time frame: 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).
Number of Participants Requiring Hospitalization During the Treatment Phase
Number of participants who required hospitalization during the treatment phase.
Time frame: Between baseline (start of treatment) and day 56 (end of treatment)
Duration (Days) of Hospitalization During the Treatment Phase
Duration (in days) of hospitalization required during treatment phase
Time frame: Between baseline (start of treatment) and day 56 (end of treatment)