COVID-19, Long COVID, Long Haul COVID, Post-Acute Sequelae of SARS-CoV-2 (PASC) Infection
Conditions
Keywords
Multi-site pain, Sleep disturbance, PASC, COVID-19, Long COVID, Coronavirus infections
Brief summary
This is a Phase 2, randomized, parallel-group, double-blind, placebo-controlled, 14-week study designed to evaluate the efficacy and safety of TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) taken once daily at bedtime for the management of multi-site pain associated with Long COVID.
Interventions
DRUGTNX-102 SL
Patients will take 1 tablet of randomly assigned study drug sublingually starting on Day 1 for 2 weeks. At the Week 2 visit, all patients will have the dose increased to 2 tablets for 12 weeks.
Patients will take 1 tablet of randomly assigned study drug sublingually starting on Day 1 for 2 weeks. At the Week 2 visit, all patients will have the dose increased to 2 tablets for 12 weeks.
Sponsors
Tonix Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Major Inclusion Criteria: * The patient is male or female, 18 to 65 years of age, inclusive. * The patient has a polymerase chain reaction (PCR) confirmed history of SARS-CoV-2 infection at least 3 months prior to enrollment, based on a documented written positive viral test at the time of active infection. * The patient has new onset or significant worsening of pain that coincides with a prior COVID-19 infection and has symptoms that have been generally present for at least 3 months but no longer than 18 months. Major
Exclusion criteria
* The patient has been diagnosed with infectious or inflammatory arthritis (eg, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis), systemic lupus erythematosus, untreated or active gout (ie, any acute attack within past 2 years is exclusionary), or meets criteria for another type of systemic autoimmune disease (eg, Sjogren's disease). * The patient has been diagnosed with a complex regional pain syndrome, fibromyalgia, failed back surgery syndrome, persistent or prevalent pain symptoms related to systemic disease (eg, diabetic peripheral neuropathy, post-herpetic neuropathy), untreated hyperparathyroidism, or a history of prior surgery, trauma, organ or tissue damage, or other source of pain that, in the Investigator's opinion, would confound or interfere with the assessment of the patient's symptoms or require excluded therapies during the patient's study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Daily Diary Pain NRS | Week 14 | Change from Baseline in the diary Numeric Rating Scale (NRS) weekly average of daily self-reported worst Long COVID pain intensity scores at the Week 14 endpoint. Scores range from 0 to 10 where a higher score means worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Daily Diary Sleep Quality NRS | Week 14 | Mean change from baseline in the weekly average of the daily diary numeric rating scale (NRS) assessment of sleep quality at the Week 14 endpoint. Scores range from 0 to 10 where a higher score means worse outcome. |
| PROMIS Fatigue -Short Form 8a | Week 14 | Change from Baseline in the Patient Reported Outcomes Measurement Information System (PROMIS) score for fatigue at the Week 14 endpoint. Subjects are asked to reflect on their fatigue symptoms in the past 7 days and respond to 8 questions on a 5 point scale (1 to 5) where a higher score indicates a worse outcome. The total score is reported on a range of 8 to 40. Raw scores are converted to T-scores based on US population with score of 50 as average with a standard deviation of 10. |
| PROMIS Cognitive Function - Abilities-Short Form 8a | Week 14 | Change from Baseline in the Patient Reported Outcomes Measurement Information System (PROMIS) score for cognitive function at the Week 14 endpoint. Subjects are asked to reflect on their cognitive function and abilities in the past 7 days and respond to 8 questions on a 5 point scale (1 to 5) where a higher score indicates a worse outcome. The total score is reported on a range of 8 to 40. Raw scores are converted to T-scores based on US population with score of 50 as average with a standard deviation of 10. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TNX-102 SL Tablet, 5.6 mg 1 x TNX-102 SL 2.8 mg Tablet taken sublingually each day at bedtime for 2 weeks, then 2 x TNX-102 SL 2.8 mg (5.6 mg) Tablet taken sublingually each day at bedtime for 12 weeks.
TNX-102 SL: Patients will take 1 tablet of randomly assigned study drug sublingually starting on Day 1 for 2 weeks. At the Week 2 visit, all patients will have the dose increased to 2 tablets for 12 weeks. | 32 |
| Placebo SL Tablet 1 x Placebo Tablet taken sublingually each day at bedtime for 2 weeks, then 2 x Placebo Tablet taken sublingually each day at bedtime for 12 weeks.
Placebo SL Tablet: Patients will take 1 tablet of randomly assigned study drug sublingually starting on Day 1 for 2 weeks. At the Week 2 visit, all patients will have the dose increased to 2 tablets for 12 weeks. | 31 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 3 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | TNX-102 SL Tablet, 5.6 mg | Placebo SL Tablet | Total |
|---|---|---|---|
| Age, Continuous | 48.6 years STANDARD_DEVIATION 8.8 | 51.4 years STANDARD_DEVIATION 10.01 | 50.0 years STANDARD_DEVIATION 9.45 |
| BMI | 29.78 kg/m^2 STANDARD_DEVIATION 4.067 | 29.49 kg/m^2 STANDARD_DEVIATION 4.439 | 29.64 kg/m^2 STANDARD_DEVIATION 4.222 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 5 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 21 Participants | 24 Participants | 45 Participants |
| Sex: Female, Male Female | 21 Participants | 25 Participants | 46 Participants |
| Sex: Female, Male Male | 11 Participants | 6 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 31 |
| other Total, other adverse events | 12 / 32 | 2 / 31 |
| serious Total, serious adverse events | 0 / 32 | 0 / 31 |
Outcome results
Primary
Daily Diary Pain NRS
Change from Baseline in the diary Numeric Rating Scale (NRS) weekly average of daily self-reported worst Long COVID pain intensity scores at the Week 14 endpoint. Scores range from 0 to 10 where a higher score means worse outcome.
Time frame: Week 14
Population: Intention-to-treat (ITT) population defined as all patients who were randomized and had at least one post-baseline daily diary entry.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TNX-102 SL Tablet, 5.6 mg | Daily Diary Pain NRS | -2.2 units on a scale | Standard Error 0.34 |
| Placebo SL Tablet | Daily Diary Pain NRS | -2.0 units on a scale | Standard Error 0.35 |
Secondary
Daily Diary Sleep Quality NRS
Mean change from baseline in the weekly average of the daily diary numeric rating scale (NRS) assessment of sleep quality at the Week 14 endpoint. Scores range from 0 to 10 where a higher score means worse outcome.
Time frame: Week 14
Population: Intention-to-treat (ITT) population defined as all patients who were randomized and had at least one post-baseline daily diary entry.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TNX-102 SL Tablet, 5.6 mg | Daily Diary Sleep Quality NRS | -2.1 units on a scale | Standard Error 0.38 |
| Placebo SL Tablet | Daily Diary Sleep Quality NRS | -1.6 units on a scale | Standard Error 0.39 |
Secondary
PROMIS Cognitive Function - Abilities-Short Form 8a
Change from Baseline in the Patient Reported Outcomes Measurement Information System (PROMIS) score for cognitive function at the Week 14 endpoint. Subjects are asked to reflect on their cognitive function and abilities in the past 7 days and respond to 8 questions on a 5 point scale (1 to 5) where a higher score indicates a worse outcome. The total score is reported on a range of 8 to 40. Raw scores are converted to T-scores based on US population with score of 50 as average with a standard deviation of 10.
Time frame: Week 14
Population: Intention-to-treat (ITT) population defined as all patients who were randomized and had at least one post-baseline daily diary entry.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TNX-102 SL Tablet, 5.6 mg | PROMIS Cognitive Function - Abilities-Short Form 8a | 5.4 T-score | Standard Error 1.55 |
| Placebo SL Tablet | PROMIS Cognitive Function - Abilities-Short Form 8a | 3.5 T-score | Standard Error 1.55 |
Secondary
PROMIS Fatigue -Short Form 8a
Change from Baseline in the Patient Reported Outcomes Measurement Information System (PROMIS) score for fatigue at the Week 14 endpoint. Subjects are asked to reflect on their fatigue symptoms in the past 7 days and respond to 8 questions on a 5 point scale (1 to 5) where a higher score indicates a worse outcome. The total score is reported on a range of 8 to 40. Raw scores are converted to T-scores based on US population with score of 50 as average with a standard deviation of 10.
Time frame: Week 14
Population: Intention-to-treat (ITT) population defined as all patients who were randomized and had at least one post-baseline daily diary entry.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| TNX-102 SL Tablet, 5.6 mg | PROMIS Fatigue -Short Form 8a | -8.0 T-score | Standard Error 1.65 |
| Placebo SL Tablet | PROMIS Fatigue -Short Form 8a | -3.2 T-score | Standard Error 1.68 |