Fibromyalgia
Conditions
Keywords
Pain, Sleep, Fibromyalgia, FM
Brief summary
This is a Phase 3, 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 daily at bedtime for the treatment of fibromyalgia.
Interventions
DRUGTNX-102 SL Tablet, 5.6 mg
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
* The patient is male or female 18 to 65 years of age, inclusive. * The patient has a diagnosis of primary FM as defined by the 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria (American College of Rheumatology Preliminary Diagnostic Criteria)
Exclusion criteria
* The patient has been diagnosed with infectious or inflammatory arthritis (e.g., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis), systemic lupus erythematosus, untreated or active gout (ie, any acute attacks within past 2 years is exclusionary), or meets criteria for other type of systemic autoimmune disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to the Week 14 Endpoint in the Diary NRS Weekly Average of Daily Self Reported Average Pain Severity Scores. | Baseline (Day -7 to Day -1), Week 14 | Change from Baseline to the Week 14 endpoint in the diary Numerical Rating Scale (NRS) weekly average of daily self-reported average pain severity scores. Scores range from 0 to 10 where a higher score means worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Fibromyalgia Impact Questionnaire - Revised (FIQ-R) Symptoms Domain Score at the Week 14 Endpoint | Day 1, Week 14 | Change from Baseline in the FIQ-R Symptoms domain score at the Week 14 endpoint. Scores on the symptoms domain range from 0 to 90 where a higher score means worse outcome. |
| Change From Baseline in the FIQ-R Function Domain Score at the Week 14 Endpoint | Day 1, Week 14 | The FIQ-R is a validated questionnaire. Scores on the function domain range from 0 to 90 where a higher score means worse outcome. |
| Proportion of Patients With a Patient's Global Impression of Change (PGIC) Rating of Very Much Improved or Much Improved at the Week 14 Endpoint | Week 14 | The PGIC is a fibromyalgia specific validated instrument on a scale of 1 to 7, where a score of 1 indicates the highest level of improvement and a score of 7 indicates a much worse outcome. |
| Change From Baseline in the PROMIS Score for Fatigue at the Week 14 Endpoint | Day 1, Week 14 | The PROMIS fatigue short form 8a consists of 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. |
| Change From Baseline in the Weekly Average of the Daily Diary Assessment of Sleep Quality at the Week 14 Endpoint | Baseline (Day -7 to Day -1), Week 14 | Patients provide a daily numeric assessment of their sleep quality for the previous night, via an electronic diary, using an 11-point NRS. Scores range from 0 (best possible sleep) to 10 (worst possible sleep). |
| Change From Baseline in the Patient Reported Outcomes Measurement Information System (PROMIS) Score for Sleep Disturbance at the Week 14 Endpoint | Day 1, Week 14 | The PROMIS Sleep disturbance short form 8a consists of 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. | 231 |
| 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. | 226 |
| Total | 457 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 14 | 8 |
| Overall Study | Lack of Efficacy | 2 | 8 |
| Overall Study | Lost to Follow-up | 10 | 10 |
| Overall Study | Non-Compliance | 3 | 2 |
| Overall Study | Patient should not have been randomized due to ongoing unstable medical condition | 0 | 1 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Withdrawal by Subject | 14 | 16 |
Baseline characteristics
| Characteristic | Placebo SL Tablet | Total | TNX-102 SL Tablet, 5.6 mg |
|---|---|---|---|
| Age, Continuous | 49.5 years STANDARD_DEVIATION 11.2 | 49.4 years STANDARD_DEVIATION 10.88 | 49.3 years STANDARD_DEVIATION 10.45 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 35 Participants | 71 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 190 Participants | 385 Participants | 195 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 6 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 27 Participants | 59 Participants | 32 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 2 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 | 192 Participants | 386 Participants | 194 Participants |
| Sex: Female, Male Female | 212 Participants | 436 Participants | 224 Participants |
| Sex: Female, Male Male | 14 Participants | 21 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 231 | 0 / 226 |
| other Total, other adverse events | 78 / 231 | 4 / 226 |
| serious Total, serious adverse events | 2 / 231 | 3 / 226 |
Outcome results
Primary
Change From Baseline to the Week 14 Endpoint in the Diary NRS Weekly Average of Daily Self Reported Average Pain Severity Scores.
Change from Baseline to the Week 14 endpoint in the diary Numerical Rating Scale (NRS) weekly average of daily self-reported average pain severity scores. Scores range from 0 to 10 where a higher score means worse outcome.
Time frame: Baseline (Day -7 to Day -1), Week 14
Population: Intention-To-Treat (ITT) population: all patients who were randomized. This is the primary population for efficacy analyses, and patients will be analyzed based on their randomized treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TNX-102 SL Tablet, 5.6 mg | Change From Baseline to the Week 14 Endpoint in the Diary NRS Weekly Average of Daily Self Reported Average Pain Severity Scores. | -1.8 score on a scale |
| Placebo SL Tablet | Change From Baseline to the Week 14 Endpoint in the Diary NRS Weekly Average of Daily Self Reported Average Pain Severity Scores. | -1.2 score on a scale |
Secondary
Change From Baseline in the Fibromyalgia Impact Questionnaire - Revised (FIQ-R) Symptoms Domain Score at the Week 14 Endpoint
Change from Baseline in the FIQ-R Symptoms domain score at the Week 14 endpoint. Scores on the symptoms domain range from 0 to 90 where a higher score means worse outcome.
Time frame: Day 1, Week 14
Population: Intention-To-Treat (ITT) population: all patients who were randomized. This is the primary population for efficacy analyses, and patients will be analyzed based on their randomized treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TNX-102 SL Tablet, 5.6 mg | Change From Baseline in the Fibromyalgia Impact Questionnaire - Revised (FIQ-R) Symptoms Domain Score at the Week 14 Endpoint | -16.0 score on a scale |
| Placebo SL Tablet | Change From Baseline in the Fibromyalgia Impact Questionnaire - Revised (FIQ-R) Symptoms Domain Score at the Week 14 Endpoint | -8.4 score on a scale |
Secondary
Change From Baseline in the FIQ-R Function Domain Score at the Week 14 Endpoint
The FIQ-R is a validated questionnaire. Scores on the function domain range from 0 to 90 where a higher score means worse outcome.
Time frame: Day 1, Week 14
Population: Intention-To-Treat (ITT) population: all patients who were randomized. This is the primary population for efficacy analyses, and patients will be analyzed based on their randomized treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TNX-102 SL Tablet, 5.6 mg | Change From Baseline in the FIQ-R Function Domain Score at the Week 14 Endpoint | -12.2 score on a scale |
| Placebo SL Tablet | Change From Baseline in the FIQ-R Function Domain Score at the Week 14 Endpoint | -6.8 score on a scale |
Secondary
Change From Baseline in the Patient Reported Outcomes Measurement Information System (PROMIS) Score for Sleep Disturbance at the Week 14 Endpoint
The PROMIS Sleep disturbance short form 8a consists of 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: Day 1, Week 14
Population: Intention-To-Treat (ITT) population: all patients who were randomized. This is the primary population for efficacy analyses, and patients will be analyzed based on their randomized treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TNX-102 SL Tablet, 5.6 mg | Change From Baseline in the Patient Reported Outcomes Measurement Information System (PROMIS) Score for Sleep Disturbance at the Week 14 Endpoint | -8.4 T-score |
| Placebo SL Tablet | Change From Baseline in the Patient Reported Outcomes Measurement Information System (PROMIS) Score for Sleep Disturbance at the Week 14 Endpoint | -4.2 T-score |
Secondary
Change From Baseline in the PROMIS Score for Fatigue at the Week 14 Endpoint
The PROMIS fatigue short form 8a consists of 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: Day 1, Week 14
Population: Intention-To-Treat (ITT) population: all patients who were randomized. This is the primary population for efficacy analyses, and patients will be analyzed based on their randomized treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TNX-102 SL Tablet, 5.6 mg | Change From Baseline in the PROMIS Score for Fatigue at the Week 14 Endpoint | -7.2 T-score |
| Placebo SL Tablet | Change From Baseline in the PROMIS Score for Fatigue at the Week 14 Endpoint | -4.2 T-score |
Secondary
Change From Baseline in the Weekly Average of the Daily Diary Assessment of Sleep Quality at the Week 14 Endpoint
Patients provide a daily numeric assessment of their sleep quality for the previous night, via an electronic diary, using an 11-point NRS. Scores range from 0 (best possible sleep) to 10 (worst possible sleep).
Time frame: Baseline (Day -7 to Day -1), Week 14
Population: Intention-To-Treat (ITT) population: all patients who were randomized. This is the primary population for efficacy analyses, and patients will be analyzed based on their randomized treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TNX-102 SL Tablet, 5.6 mg | Change From Baseline in the Weekly Average of the Daily Diary Assessment of Sleep Quality at the Week 14 Endpoint | -1.8 score on a scale |
| Placebo SL Tablet | Change From Baseline in the Weekly Average of the Daily Diary Assessment of Sleep Quality at the Week 14 Endpoint | -1.2 score on a scale |
Secondary
Proportion of Patients With a Patient's Global Impression of Change (PGIC) Rating of Very Much Improved or Much Improved at the Week 14 Endpoint
The PGIC is a fibromyalgia specific validated instrument on a scale of 1 to 7, where a score of 1 indicates the highest level of improvement and a score of 7 indicates a much worse outcome.
Time frame: Week 14
Population: Intention-To-Treat (ITT) population: all patients who were randomized. This is the primary population for efficacy analyses, and patients will be analyzed based on their randomized treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TNX-102 SL Tablet, 5.6 mg | Proportion of Patients With a Patient's Global Impression of Change (PGIC) Rating of Very Much Improved or Much Improved at the Week 14 Endpoint | 66 Participants |
| Placebo SL Tablet | Proportion of Patients With a Patient's Global Impression of Change (PGIC) Rating of Very Much Improved or Much Improved at the Week 14 Endpoint | 34 Participants |