Erythropoietic Protoporphyria (EPP)
Conditions
Brief summary
The purpose of this study is to investigate the efficacy and safety of MT-7117 on sunlight exposure duration without symptoms and tolerance in subjects with EPP.
Detailed description
This is a Phase 2, randomized, double-blind, placebo controlled study to assess the efficacy, tolerability, and safety of MT-7117 in subjects with EPP. The study consists of a 2 week screening period, a 16 week double-blind treatment period, and a 6 week follow-up period at Week 22. The total participation period is approximately 24 weeks.
Interventions
DRUGPlacebo
Placebo QD, oral, 16 weeks
DRUGMT-7117 low dose
MT-7117 low dose QD, oral, 16 weeks
MT-7117 high dose QD, oral, 16 weeks
Sponsors
Tanabe Pharma America, 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 75 Years
Healthy volunteers
No
Inclusion criteria
Additional screening criteria check may apply for qualification. Inclusion Criteria: * 1\. Subjects provided written informed consent to participate. * 2\. Male and female subjects with a confirmed diagnosis of EPP based on medical history, aged 18 years to 75 years, inclusive, at Screening. * 3\. Subjects are willing and able to travel to the study sites for all scheduled visits. * 4\. In the Investigator's opinion, subject is able to understand the nature of the study and any risks involved in participation, and willing to cooperate and comply with the protocol restrictions and requirements (including travel).
Exclusion criteria
* 1\. History or presence of photodermatoses other than EPP. * 2\. Subjects who are unwilling or unable to go outside during daylight hours (e.g., between 1 hour post sunrise and 1 hour pre-sunset) during the study. * 3\. Presence of clinically significant hepatobiliary disease based on LFT values at Screening. * 4\. Subjects with AST, ALT, ALP ≥3.0 × upper limit of normal (ULN) or total bilirubin \>1.5 × ULN at Screening. * 5\. Subjects with or having a history (in the last 2 years) of excessive alcohol intake in the opinion of the Investigator. * 6\. History or presence of melanoma and/or atypical nevus at Screening. * 7\. History of familial melanoma (defined as having 2 or more first-degree relatives, such as parents, sibling and/or child). * 8\. History or presence of pre-malignant skin lesion squamous cell carcinoma, basal cell carcinoma, or other malignant skin lesions. * 9\. History or presence of psychiatric disease judged to be clinically significant by the Investigator and which may interfere with the study evaluation and/or safety of the subjects. * 10\. Presence of clinically significant acute or chronic renal disease based upon the subject's medical records including hemodialysis; and a serum creatinine level of greater than 1.2 mg/dL or a glomerular filtration rate (GFR) \<60 ml/min. * 11\. Presence of any clinically significant disease or laboratory abnormality which, in the opinion of the Investigator, can interfere with the study objectives and/or safety of the subjects. * 12\. Pregnancy or lactation. * 13\. Females of child bearing potential and male subjects with partners of child-bearing potential unwilling to use adequate contraception measures as described in the protocol. * 14\. Treatment with phototherapy within 3 months before Randomization (Visit 2). * 15\. Treatment with afamelanotide within 3 months before Randomization (Visit 2). * 16\. Treatment with cimetidine within 4 weeks before Randomization (Visit 2). * 17\. Treatment with antioxidant agents at doses which, in the opinion of the Investigator, may affect study endpoints (including but not limited to beta-carotene, cysteine, pyridoxine) within 4 weeks before Randomization (Visit 2). * 18\. Chronic treatment with prescription-based analgesic agents including but not limited to opioids and opioid derivatives such as morphine, hydrocodone, oxycodone or their combination with other analgesics or non-steroidal anti-inflammatory drug (NSAID, as Percocet and Vicodin-like prescription drugs) within 4 weeks before Randomization (Visit 2). * 19\. Treatment with any drugs or supplements which, in the opinion of the Investigator, can interfere with the objectives of the study or safety of the subjects. * 20\. Previous exposure to MT 7117. * 21\. Previous treatment with any investigational agent within 12 weeks before Screening OR 5 half-lives of the investigational product (whichever is longer).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average Daily Time (Minutes) to First Prodromal Symptom Associated With Sunlight Exposure Between Hour Post Sunrise and 1 Hour Pre-Sunset at Week 16. | Baseline (Week 0) and Week 16 | Duration in minutes, of sunlight exposure between 1 hour post sunrise and 1 hour pre-sunset. The average Duration in minutes, of sunlight exposure before the first prodromal symptom between 1 hour post sunrise and 1 hour pre-sunset. The average duration means that average of daily durations in 14-day windows before Day 1 (or week 16 Day) applied. |
| Change From Baseline in Average Daily Duration (Minutes) of Sunlight Exposure Between 1 Hour Post Sunrise and 1 Hour Pre-Sunset Without Prodromal Symptoms at Week 16 | Baseline (Week 0), and Week 16 | Change from baseline to week 16 in Average Daily Duration (Minutes) of Sunlight Exposure sums any sunlight exposure time excluding any overlapped time with prodromal symptoms, including if the patients go out multiple times on the same day after the prodromal symptom had previously ended. |
| Change From Baseline in Average Daily Mean Duration (Minutes) of Sunlight Exposure Between 1 Hour Post Sunrise and 1 Hour Pre-Sunset Without Prodromal Symptoms at Week 16 | Baseline (Week 0), and Week 16 | Change from baseline to week 16 in Average Daily Mean Duration (Minutes) of Sunlight Exposure without prodromal symptoms divided by the number of sunlight exposures periods applicable that day. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average Daily Duration (Minutes) of Prodromal Symptoms at 16-Week Double-Blind Treatment Period | Baseline (Week 0), and Week 16 | — |
| Percent Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16. | Baseline (Week 0), Week 8, and Week 16 | — |
| Total Number of Pain Events During 16-Week Double-Blind Treatment Period | Week 16 | — |
| Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16. | Baseline (Week 0), Week 8, and Week 16 | Pigmentation will be assessed in melanin density which are numeric scores measured by spectrophotometer on 6 skin segments (forehead, left cheek, right inside upper arm, left medial forearm, right-hand side of abdomen, and left-hand side of buttock). |
| Total Number of Sunlight Exposure Episodes With Prodromal Symptoms During 16-Week Double-Blind Treatment Period | Week 16 | — |
| Change From Baseline in Average Daily Mean Intensity of Prodromal Symptoms During 16-week Double-blind Treatment Period in 11-point Likert Scale | Baseline (Week 0), and Week 16 | The Intensity of Prodromal Symptoms is measured by 11-point Likert scale ranges from 0 (no symptom) to 10 (greatest severity of symptom). |
Other
| Measure | Time frame |
|---|---|
| Total Number of Sunlight Exposure Episodes | Baseline (Week 0) and Week 16 |
| The Quality of Life as Measured by the Patient Reported Outcomes Measurement Information System (PROMIS) 57 | Baseline (Week 0) and Week 16 |
| Change in Pigmentation as Measured by Melanin Density | Baseline (Week 0) and Week 16 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MT-7117 Low Dose MT-7117 low dose: MT-7117 low dose QD, oral, 16 weeks | 33 |
| MT-7117 High Dose MT-7117 high dose: MT-7117 high dose QD, oral, 16 weeks | 34 |
| Placebo Placebo: Placebo QD, oral, 16 weeks | 35 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 0 |
| Overall Study | CS Adverse Findings from Post- Baseline Nevi Evaluation | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 4 |
Baseline characteristics
| Characteristic | MT-7117 Low Dose | MT-7117 High Dose | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 41.8 years STANDARD_DEVIATION 12.8 | 41.9 years STANDARD_DEVIATION 14 | 38.1 years STANDARD_DEVIATION 12.6 | 40.6 years STANDARD_DEVIATION 13.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 32 Participants | 34 Participants | 98 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 33 Participants | 33 Participants | 32 Participants | 98 Participants |
| Sex: Female, Male Female | 15 Participants | 25 Participants | 13 Participants | 53 Participants |
| Sex: Female, Male Male | 18 Participants | 9 Participants | 22 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 35 | 0 / 34 |
| other Total, other adverse events | 31 / 33 | 34 / 35 | 31 / 34 |
| serious Total, serious adverse events | 1 / 33 | 0 / 35 | 0 / 34 |
Outcome results
Primary
Change From Baseline in Average Daily Duration (Minutes) of Sunlight Exposure Between 1 Hour Post Sunrise and 1 Hour Pre-Sunset Without Prodromal Symptoms at Week 16
Change from baseline to week 16 in Average Daily Duration (Minutes) of Sunlight Exposure sums any sunlight exposure time excluding any overlapped time with prodromal symptoms, including if the patients go out multiple times on the same day after the prodromal symptom had previously ended.
Time frame: Baseline (Week 0), and Week 16
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-7117 Low Dose | Change From Baseline in Average Daily Duration (Minutes) of Sunlight Exposure Between 1 Hour Post Sunrise and 1 Hour Pre-Sunset Without Prodromal Symptoms at Week 16 | 72.6 Minutes | Standard Deviation 76.2 |
| MT-7117 High Dose | Change From Baseline in Average Daily Duration (Minutes) of Sunlight Exposure Between 1 Hour Post Sunrise and 1 Hour Pre-Sunset Without Prodromal Symptoms at Week 16 | 86.1 Minutes | Standard Deviation 83.9 |
| Placebo | Change From Baseline in Average Daily Duration (Minutes) of Sunlight Exposure Between 1 Hour Post Sunrise and 1 Hour Pre-Sunset Without Prodromal Symptoms at Week 16 | 19.9 Minutes | Standard Deviation 63.2 |
Primary
Change From Baseline in Average Daily Mean Duration (Minutes) of Sunlight Exposure Between 1 Hour Post Sunrise and 1 Hour Pre-Sunset Without Prodromal Symptoms at Week 16
Change from baseline to week 16 in Average Daily Mean Duration (Minutes) of Sunlight Exposure without prodromal symptoms divided by the number of sunlight exposures periods applicable that day.
Time frame: Baseline (Week 0), and Week 16
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-7117 Low Dose | Change From Baseline in Average Daily Mean Duration (Minutes) of Sunlight Exposure Between 1 Hour Post Sunrise and 1 Hour Pre-Sunset Without Prodromal Symptoms at Week 16 | 70.2 Minutes | Standard Deviation 73.4 |
| MT-7117 High Dose | Change From Baseline in Average Daily Mean Duration (Minutes) of Sunlight Exposure Between 1 Hour Post Sunrise and 1 Hour Pre-Sunset Without Prodromal Symptoms at Week 16 | 59.3 Minutes | Standard Deviation 85.2 |
| Placebo | Change From Baseline in Average Daily Mean Duration (Minutes) of Sunlight Exposure Between 1 Hour Post Sunrise and 1 Hour Pre-Sunset Without Prodromal Symptoms at Week 16 | 12.8 Minutes | Standard Deviation 46.9 |
Primary
Change From Baseline in Average Daily Time (Minutes) to First Prodromal Symptom Associated With Sunlight Exposure Between Hour Post Sunrise and 1 Hour Pre-Sunset at Week 16.
Duration in minutes, of sunlight exposure between 1 hour post sunrise and 1 hour pre-sunset. The average Duration in minutes, of sunlight exposure before the first prodromal symptom between 1 hour post sunrise and 1 hour pre-sunset. The average duration means that average of daily durations in 14-day windows before Day 1 (or week 16 Day) applied.
Time frame: Baseline (Week 0) and Week 16
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-7117 Low Dose | Change From Baseline in Average Daily Time (Minutes) to First Prodromal Symptom Associated With Sunlight Exposure Between Hour Post Sunrise and 1 Hour Pre-Sunset at Week 16. | 74.7 Minutes | Standard Deviation 76.8 |
| MT-7117 High Dose | Change From Baseline in Average Daily Time (Minutes) to First Prodromal Symptom Associated With Sunlight Exposure Between Hour Post Sunrise and 1 Hour Pre-Sunset at Week 16. | 92.4 Minutes | Standard Deviation 100 |
| Placebo | Change From Baseline in Average Daily Time (Minutes) to First Prodromal Symptom Associated With Sunlight Exposure Between Hour Post Sunrise and 1 Hour Pre-Sunset at Week 16. | 21.0 Minutes | Standard Deviation 63.4 |
Secondary
Change From Baseline in Average Daily Duration (Minutes) of Prodromal Symptoms at 16-Week Double-Blind Treatment Period
Time frame: Baseline (Week 0), and Week 16
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-7117 Low Dose | Change From Baseline in Average Daily Duration (Minutes) of Prodromal Symptoms at 16-Week Double-Blind Treatment Period | 55.3 Minutes | Standard Deviation 321 |
| MT-7117 High Dose | Change From Baseline in Average Daily Duration (Minutes) of Prodromal Symptoms at 16-Week Double-Blind Treatment Period | 111.0 Minutes | Standard Deviation 466.1 |
| Placebo | Change From Baseline in Average Daily Duration (Minutes) of Prodromal Symptoms at 16-Week Double-Blind Treatment Period | 83.3 Minutes | Standard Deviation 267.2 |
Secondary
Change From Baseline in Average Daily Mean Intensity of Prodromal Symptoms During 16-week Double-blind Treatment Period in 11-point Likert Scale
The Intensity of Prodromal Symptoms is measured by 11-point Likert scale ranges from 0 (no symptom) to 10 (greatest severity of symptom).
Time frame: Baseline (Week 0), and Week 16
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MT-7117 Low Dose | Change From Baseline in Average Daily Mean Intensity of Prodromal Symptoms During 16-week Double-blind Treatment Period in 11-point Likert Scale | Baseline | 2.0 score on a scale | Standard Deviation 1.1 |
| MT-7117 Low Dose | Change From Baseline in Average Daily Mean Intensity of Prodromal Symptoms During 16-week Double-blind Treatment Period in 11-point Likert Scale | Week 16 | 1.7 score on a scale | Standard Deviation 1.1 |
| MT-7117 High Dose | Change From Baseline in Average Daily Mean Intensity of Prodromal Symptoms During 16-week Double-blind Treatment Period in 11-point Likert Scale | Baseline | 2.1 score on a scale | Standard Deviation 0.9 |
| MT-7117 High Dose | Change From Baseline in Average Daily Mean Intensity of Prodromal Symptoms During 16-week Double-blind Treatment Period in 11-point Likert Scale | Week 16 | 2.4 score on a scale | Standard Deviation 1.7 |
| Placebo | Change From Baseline in Average Daily Mean Intensity of Prodromal Symptoms During 16-week Double-blind Treatment Period in 11-point Likert Scale | Baseline | 2.0 score on a scale | Standard Deviation 1.1 |
| Placebo | Change From Baseline in Average Daily Mean Intensity of Prodromal Symptoms During 16-week Double-blind Treatment Period in 11-point Likert Scale | Week 16 | 2.4 score on a scale | Standard Deviation 1.4 |
Secondary
Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16.
Pigmentation will be assessed in melanin density which are numeric scores measured by spectrophotometer on 6 skin segments (forehead, left cheek, right inside upper arm, left medial forearm, right-hand side of abdomen, and left-hand side of buttock).
Time frame: Baseline (Week 0), Week 8, and Week 16
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MT-7117 Low Dose | Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16. | Change from Baseline at Week 8 | 1.4635 unitless | Standard Deviation 3.1644 |
| MT-7117 Low Dose | Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16. | Change from Baseline at Week 16 | 1.1413 unitless | Standard Deviation 0.7285 |
| MT-7117 High Dose | Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16. | Change from Baseline at Week 8 | 1.6557 unitless | Standard Deviation 2.2099 |
| MT-7117 High Dose | Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16. | Change from Baseline at Week 16 | 1.5307 unitless | Standard Deviation 0.6881 |
| Placebo | Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16. | Change from Baseline at Week 8 | 0.1390 unitless | Standard Deviation 0.3376 |
| Placebo | Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16. | Change from Baseline at Week 16 | 0.1639 unitless | Standard Deviation 0.3939 |
Secondary
Percent Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16.
Time frame: Baseline (Week 0), Week 8, and Week 16
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MT-7117 Low Dose | Percent Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16. | % Change from Baseline at Week 8 | 30.4135 percent change | Standard Deviation 32.8302 |
| MT-7117 Low Dose | Percent Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16. | % Change from Baseline at Week 16 | 44.0135 percent change | Standard Deviation 43.7325 |
| MT-7117 High Dose | Percent Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16. | % Change from Baseline at Week 8 | 42.5543 percent change | Standard Deviation 38.839 |
| MT-7117 High Dose | Percent Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16. | % Change from Baseline at Week 16 | 56.2871 percent change | Standard Deviation 41.066 |
| Placebo | Percent Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16. | % Change from Baseline at Week 8 | 4.2394 percent change | Standard Deviation 11.9435 |
| Placebo | Percent Change From Baseline in Pigmentation as Measured by Melanin Density for Average of 6 Skin Segments at Week 8 and Week 16. | % Change from Baseline at Week 16 | 7.4214 percent change | Standard Deviation 16.7074 |
Secondary
Total Number of Pain Events During 16-Week Double-Blind Treatment Period
Time frame: Week 16
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-7117 Low Dose | Total Number of Pain Events During 16-Week Double-Blind Treatment Period | 4.0 pain events | Standard Deviation 6.4 |
| MT-7117 High Dose | Total Number of Pain Events During 16-Week Double-Blind Treatment Period | 3.3 pain events | Standard Deviation 2.8 |
| Placebo | Total Number of Pain Events During 16-Week Double-Blind Treatment Period | 5.4 pain events | Standard Deviation 4.9 |
Secondary
Total Number of Sunlight Exposure Episodes With Prodromal Symptoms During 16-Week Double-Blind Treatment Period
Time frame: Week 16
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MT-7117 Low Dose | Total Number of Sunlight Exposure Episodes With Prodromal Symptoms During 16-Week Double-Blind Treatment Period | 8.6 sunlight exposure episodes | Standard Deviation 9.3 |
| MT-7117 High Dose | Total Number of Sunlight Exposure Episodes With Prodromal Symptoms During 16-Week Double-Blind Treatment Period | 7.7 sunlight exposure episodes | Standard Deviation 6.6 |
| Placebo | Total Number of Sunlight Exposure Episodes With Prodromal Symptoms During 16-Week Double-Blind Treatment Period | 11.1 sunlight exposure episodes | Standard Deviation 13.3 |
Other Pre-specified
Change in Pigmentation as Measured by Melanin Density
Time frame: Baseline (Week 0) and Week 16
Other Pre-specified
The Quality of Life as Measured by the Patient Reported Outcomes Measurement Information System (PROMIS) 57
Time frame: Baseline (Week 0) and Week 16
Other Pre-specified
Total Number of Sunlight Exposure Episodes
Time frame: Baseline (Week 0) and Week 16