Aura Migraine, Chronic Migraine, Chronic Migraine, Headache, Chronic Migraine Without Aura
Conditions
Keywords
Migraine, Chronic Migraine, Headache, Chronic Migraine Without Aura, Aura Migraine
Brief summary
This is a phase 2, double-blind, randomized, multicenter, placebo-controlled, three arm parallel study to evaluate the efficacy and safety of two different dosages (30 IU daily and 60 IU daily) of TNX-1900 in patients with chronic migraine.
Interventions
DRUGTNX-1900
Patients will spray TNX-1900 once into each nostril.
DRUGPlacebo Nasal Spray
Patients will spray placebo nasal spray once into each nostril.
Sponsors
Premier
Tonix Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
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: * Men and women aged 18 to 65 years, inclusive, at the time of Visit 1. * History of migraine with or without aura for at least 1 year and onset at \< 50 years of age. Patient must also have a history of chronic migraine \> 3 months prior to Visit 1 as defined by IHS ICHD-3 * Patients can be on stable ≤ 1 preventive medication and any number of abortive migraine medications for 90 days prior to Screening and during the study. All treatments, other than the study drug, thought to have preventive efficacy in migraine should not be started or discontinued during the entire study period. Note: Up to approximately 30% of the patients randomized into the study can be on 1 preventative medication. Once this category is filled, only patients who are not on any preventative medications can be randomized into the study. Major
Exclusion criteria
* History of cluster headache. * Presence of headaches more than 26 days a month on average for the 6 months prior to Screening. * Failed to benefit from an adequate dose and duration, in the investigator's judgment (eg, one month of β-blocker), of 3 or more migraine preventive medications. * Use of opiates or barbiturates more than 4 days per month for more than 3 consecutive months prior to Visit 1 and during the study. * Use of over-the-counter (OTC) nasal products (ie, saline spray, Neti-Pot, Naväge® etc.) during the study. * Any use of intranasal corticosteroid medications or conditions in which use of intranasal corticosteroids may be indicated during the study, eg, unstable allergic rhinitis that has previously required intranasal corticosteroids. Intranasal corticosteroid use is not allowed within 28 days of Baseline/Randomization/Visit 2 and during the treatment phase or follow-up period of the study. * Patients who recently discontinued treatment with an anti-calcitonin-gene-related peptide (CGRP) or participated in anti-CGRP clinical study must be at least 4 months from the last drug administration prior to Visit 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in the Number of Monthly Migraine Headache Days | Last 28 days before Visit 2 (Day 1) and last 28 days before Visit 5 (Week 12) | Mean change in the number of monthly migraine headache days from the last 28 days of Baseline to the last 28 days of treatment (ie, month 3). A migraine headache day is any calendar day (0:00 to 23:59) in which the patient records in the e-diary: * An attack lasting 4 hours or more and meeting the ICHD-3 criteria for migraine without aura, or * A migraine with aura, or * An attack that meets ICHD-3 criteria for probable migraine, (a migraine subtype fulfilling all but one criteria (B-D) for migraine without aura), or * An attack of any duration that was believed by the patient to be a migraine and was relieved by a triptan, ergot derivative, or other migraine-specific abortive medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in the Number of Days Using Rescue Medication | Last 28 days before Visit 2 (Day 1) treatment and last 28 days before Visit 5 (Week 12) | Mean change in the number of days using rescue medication (triptan, ergot derivative, or other migraine-specific acute medication) from the last 28 days of Baseline to the last 28 days of treatment. |
| Patient Global Impression of Change (PGIC) | Visit 5 (Week 12) | Proportion of patients with a Patient Global Impression of Change (PGIC) of 1, very much improved, or 2, much improved, at Week 12. Scores range from 1 to 7. Lower scores indicate more improvement. |
| Proportion of Patients Experiencing a ≥ 50% Reduction in the Number of Migraine Headache Days | Last 28 days before Visit 2 (Day 1) treatment and last 28 days before Visit 5 (Week 12) | Proportion of patients experiencing a ≥ 50% reduction in the number of migraine headache days from the last 28 days of Baseline to the last 28 days of treatment in each treatment group |
| Mean Change in the Number of Migraine Headache Days | Last 28 days before Visit 2 (Day 1) and average per 28 days over 12-week Treatment Period | Mean change in the number of migraine headache days from the last 28 days of Baseline to average number per 28 days over the entire 12-week duration of Treatment Period. |
| Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire | Visit 2 (Day 1) and Visit 5 (Week 12) | Mean change from Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ v2.1) at Week 12. Scores range from 0 to 100. Higher scores indicate better quality of life. |
| Mean Change in the Number of Moderate or Severe Headache Days | Last 28 days before Visit 2 (Day 1) and last 28 days before Visit 5 (Week 12) | Mean change in the number of moderate or severe headache days from the last 28 days of Baseline to the last 28 days of treatment. A moderate or severe headache day is defined as any calendar day wherein a patient records a headache or migraine of moderate or severe peak intensity in the e-diary. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo taken intranasally twice daily.
Placebo Nasal Spray: Patients will spray placebo nasal spray once into each nostril. | 27 |
| TNX-1900 Low Dose 30 IU oxytocin taken intranasally once daily. Placebo taken intranasally once daily.
TNX-1900: Patients will spray TNX-1900 once into each nostril.
Placebo Nasal Spray: Patients will spray placebo nasal spray once into each nostril. | 31 |
| TNX-1900 High Dose 30 IU oxytocin taken intranasally twice daily.
TNX-1900: Patients will spray TNX-1900 once into each nostril. | 30 |
| Total | 88 |
Baseline characteristics
| Characteristic | Placebo | Total | TNX-1900 High Dose | TNX-1900 Low Dose |
|---|---|---|---|---|
| Age, Continuous | 42.2 years STANDARD_DEVIATION 10.61 | 42.1 years STANDARD_DEVIATION 11.02 | 44.1 years STANDARD_DEVIATION 11.43 | 40.0 years STANDARD_DEVIATION 10.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 12 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 76 Participants | 28 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 14 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 24 Participants | 68 Participants | 22 Participants | 22 Participants |
| Region of Enrollment United States | 27 participants | 88 participants | 30 participants | 31 participants |
| Sex: Female, Male Female | 6 Participants | 12 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 21 Participants | 76 Participants | 28 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 31 | 0 / 30 |
| other Total, other adverse events | 6 / 27 | 10 / 31 | 5 / 30 |
| serious Total, serious adverse events | 0 / 27 | 0 / 31 | 0 / 30 |
Outcome results
Primary
Mean Change in the Number of Monthly Migraine Headache Days
Mean change in the number of monthly migraine headache days from the last 28 days of Baseline to the last 28 days of treatment (ie, month 3). A migraine headache day is any calendar day (0:00 to 23:59) in which the patient records in the e-diary: * An attack lasting 4 hours or more and meeting the ICHD-3 criteria for migraine without aura, or * A migraine with aura, or * An attack that meets ICHD-3 criteria for probable migraine, (a migraine subtype fulfilling all but one criteria (B-D) for migraine without aura), or * An attack of any duration that was believed by the patient to be a migraine and was relieved by a triptan, ergot derivative, or other migraine-specific abortive medication.
Time frame: Last 28 days before Visit 2 (Day 1) and last 28 days before Visit 5 (Week 12)
Population: Data is reported for the mITT population, which includes all randomized patients who received at least one dose of study drug and had at least one post-Baseline evaluable month (that is, at least one of the three 28-day periods has at least 14 non-missing e-diary entries).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change in the Number of Monthly Migraine Headache Days | -8.17 number of days | Standard Error 1.366 |
| TNX-1900 Low Dose | Mean Change in the Number of Monthly Migraine Headache Days | -7.78 number of days | Standard Error 1.246 |
| TNX-1900 High Dose | Mean Change in the Number of Monthly Migraine Headache Days | -5.77 number of days | Standard Error 1.301 |
Secondary
Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire
Mean change from Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ v2.1) at Week 12. Scores range from 0 to 100. Higher scores indicate better quality of life.
Time frame: Visit 2 (Day 1) and Visit 5 (Week 12)
Population: Data is reported for the mITT population, which includes all randomized patients who received at least one dose of study drug and had at least one post-Baseline evaluable month (that is, at least one of the three 28-day periods has at least 14 non-missing e-diary entries).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire | 26.07 units on a scale | Standard Error 4.154 |
| TNX-1900 Low Dose | Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire | 28.98 units on a scale | Standard Error 3.727 |
| TNX-1900 High Dose | Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire | 21.10 units on a scale | Standard Error 3.928 |
Secondary
Mean Change in the Number of Days Using Rescue Medication
Mean change in the number of days using rescue medication (triptan, ergot derivative, or other migraine-specific acute medication) from the last 28 days of Baseline to the last 28 days of treatment.
Time frame: Last 28 days before Visit 2 (Day 1) treatment and last 28 days before Visit 5 (Week 12)
Population: Data is reported for the mITT population, which includes all randomized patients who received at least one dose of study drug and had at least one post-Baseline evaluable month (that is, at least one of the three 28-day periods has at least 14 non-missing e-diary entries).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change in the Number of Days Using Rescue Medication | -3.16 days | Standard Error 0.749 |
| TNX-1900 Low Dose | Mean Change in the Number of Days Using Rescue Medication | -4.09 days | Standard Error 0.687 |
| TNX-1900 High Dose | Mean Change in the Number of Days Using Rescue Medication | -2.07 days | Standard Error 0.715 |
Secondary
Mean Change in the Number of Migraine Headache Days
Mean change in the number of migraine headache days from the last 28 days of Baseline to average number per 28 days over the entire 12-week duration of Treatment Period.
Time frame: Last 28 days before Visit 2 (Day 1) and average per 28 days over 12-week Treatment Period
Population: Data is reported for the mITT population, which includes all randomized patients who received at least one dose of study drug and had at least one post-Baseline evaluable month (that is, at least one of the three 28-day periods has at least 14 non-missing e-diary entries).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change in the Number of Migraine Headache Days | -7.09 days | Standard Error 1.208 |
| TNX-1900 Low Dose | Mean Change in the Number of Migraine Headache Days | -6.67 days | Standard Error 1.063 |
| TNX-1900 High Dose | Mean Change in the Number of Migraine Headache Days | -5.24 days | Standard Error 1.146 |
Secondary
Mean Change in the Number of Moderate or Severe Headache Days
Mean change in the number of moderate or severe headache days from the last 28 days of Baseline to the last 28 days of treatment. A moderate or severe headache day is defined as any calendar day wherein a patient records a headache or migraine of moderate or severe peak intensity in the e-diary.
Time frame: Last 28 days before Visit 2 (Day 1) and last 28 days before Visit 5 (Week 12)
Population: Data is reported for the mITT population, which includes all randomized patients who received at least one dose of study drug and had at least one post-Baseline evaluable month (that is, at least one of the three 28-day periods has at least 14 non-missing e-diary entries).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change in the Number of Moderate or Severe Headache Days | -8.39 days | Standard Error 1.372 |
| TNX-1900 Low Dose | Mean Change in the Number of Moderate or Severe Headache Days | -8.17 days | Standard Error 1.236 |
| TNX-1900 High Dose | Mean Change in the Number of Moderate or Severe Headache Days | -5.00 days | Standard Error 1.304 |
Secondary
Patient Global Impression of Change (PGIC)
Proportion of patients with a Patient Global Impression of Change (PGIC) of 1, very much improved, or 2, much improved, at Week 12. Scores range from 1 to 7. Lower scores indicate more improvement.
Time frame: Visit 5 (Week 12)
Population: Data is reported for the mITT population, which includes all randomized patients who received at least one dose of study drug and had at least one post-Baseline evaluable month (that is, at least one of the three 28-day periods has at least 14 non-missing e-diary entries).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Patient Global Impression of Change (PGIC) | 12 Participants |
| TNX-1900 Low Dose | Patient Global Impression of Change (PGIC) | 16 Participants |
| TNX-1900 High Dose | Patient Global Impression of Change (PGIC) | 14 Participants |
Secondary
Proportion of Patients Experiencing a ≥ 50% Reduction in the Number of Migraine Headache Days
Proportion of patients experiencing a ≥ 50% reduction in the number of migraine headache days from the last 28 days of Baseline to the last 28 days of treatment in each treatment group
Time frame: Last 28 days before Visit 2 (Day 1) treatment and last 28 days before Visit 5 (Week 12)
Population: Data is reported for the mITT population, which includes all randomized patients who received at least one dose of study drug and had at least one post-Baseline evaluable month (that is, at least one of the three 28-day periods has at least 14 non-missing e-diary entries).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Proportion of Patients Experiencing a ≥ 50% Reduction in the Number of Migraine Headache Days | 15 Participants |
| TNX-1900 Low Dose | Proportion of Patients Experiencing a ≥ 50% Reduction in the Number of Migraine Headache Days | 15 Participants |
| TNX-1900 High Dose | Proportion of Patients Experiencing a ≥ 50% Reduction in the Number of Migraine Headache Days | 10 Participants |