Trial Outcomes & Findings for Phase II Confirmatory Study in Erythropoietic Protoporphyria (EPP) (NCT NCT01097044)
NCT ID: NCT01097044
Last Updated: 2019-10-28
Results Overview
The amount of direct sunlight exposure between 10:00 and 15:00 hours on days when no pain was experienced (e.g. 11-point Likert pain score of 0). Time was recorded in a patient dairy using 15 minute time blocks. The pain score is measured by the 11-point Likert Pain scale with minimum of 0 and maximum of 10. Likert Pain scale of 0 represents no pain and 10 represents worst imaginable pain.
COMPLETED
PHASE2
77 participants
Daily for 6 months
2019-10-28
Participant Flow
Study Recruitment period: April2010 - July2010 Study site location: Mt. Sinai, New York Carolinas Medical Center, North Carolina University of Alabama at Birmingham, Alabama University of Utah, Utah University of Texas Medical Branch, Texas University of California, San Francisco, California
Participant milestones
| Measure |
Afamelanotide
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
Placebo
Placebo: One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
|---|---|---|
|
Overall Study
STARTED
|
39
|
38
|
|
Overall Study
COMPLETED
|
34
|
33
|
|
Overall Study
NOT COMPLETED
|
5
|
5
|
Reasons for withdrawal
| Measure |
Afamelanotide
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
Placebo
Placebo: One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
4
|
4
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Withdrawal by Sponsor
|
0
|
1
|
Baseline Characteristics
Phase II Confirmatory Study in Erythropoietic Protoporphyria (EPP)
Baseline characteristics by cohort
| Measure |
Afamelanotide
n=39 Participants
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
Placebo
n=38 Participants
Placebo: One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
Total
n=77 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.1 years
STANDARD_DEVIATION 14.5 • n=93 Participants
|
42.6 years
STANDARD_DEVIATION 15.7 • n=4 Participants
|
40.3 years
STANDARD_DEVIATION 15.2 • n=27 Participants
|
|
Age, Categorical
<=18 years
|
3 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
35 Participants
n=93 Participants
|
36 Participants
n=4 Participants
|
71 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=93 Participants
|
18 Participants
n=4 Participants
|
34 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=93 Participants
|
20 Participants
n=4 Participants
|
43 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
39 participants
n=93 Participants
|
38 participants
n=4 Participants
|
77 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Daily for 6 monthsPopulation: One active participant and one placebo participant withdrew after Baseline assessment and no data was provided for the analysis of this endpoint. The overall number of participants analyzed differs from the total number of study participants because the data was either incomplete and/or missing.
The amount of direct sunlight exposure between 10:00 and 15:00 hours on days when no pain was experienced (e.g. 11-point Likert pain score of 0). Time was recorded in a patient dairy using 15 minute time blocks. The pain score is measured by the 11-point Likert Pain scale with minimum of 0 and maximum of 10. Likert Pain scale of 0 represents no pain and 10 represents worst imaginable pain.
Outcome measures
| Measure |
Afamelanotide
n=38 Participants
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
Placebo
n=37 Participants
Placebo: One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
|---|---|---|
|
Time in Direct Sunlight Between 10:00-15:00 on Pain-free Days
|
8.25 Hours
Interval 0.0 to 48.3
|
0.75 Hours
Interval 0.0 to 71.3
|
SECONDARY outcome
Timeframe: Daily for 6 monthsPopulation: One active participant and one placebo participant withdrew after Baseline assessment and no data was provided for the analysis of this endpoint. The overall number of participants analyzed differs from the total number of study participants because the data was either incomplete and/or missing.
The days on which the participant experienced pain as a result of phototoxic reactions (caused by exposure to natural light) was recorded in a study diary. On each day such a reaction occurred, the participant scored the level of pain using an 11-point Likert pain scale, with minimum of 0 and maximum of 10. The 11-point Likert pain scale with a value of 0 represents no pain and 10 represents worst imaginable pain. The maximum severity of a phototoxic reaction was determined by the highest daily 11-point Likert scale score that occurred during that phototoxic reaction.
Outcome measures
| Measure |
Afamelanotide
n=38 Participants
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
Placebo
n=37 Participants
Placebo: One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
|---|---|---|
|
Maximum Severity of Phototoxic Reaction Experienced by Participants
|
5.0 score on a scale
Interval 0.0 to 8.0
|
5.0 score on a scale
Interval 0.0 to 10.0
|
SECONDARY outcome
Timeframe: Day 0, Day 60, Day 120, Day 180Population: One active participant and one placebo participant withdrew after Baseline assessment and no data was provided for the analysis of this endpoint. The overall number of participants analyzed differs from the total number of study participants because the data was either incomplete and/or missing.
Erythropoietic Protoporphyria Quality of Life Measure (EPP-QoL) is used to measure the quality of life of participants. The total EPP-QoL score ranges from 0 to 100, with a score of 0 as the worst quality of life and score of 100 as the best quality of life.
Outcome measures
| Measure |
Afamelanotide
n=38 Participants
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
Placebo
n=37 Participants
Placebo: One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
|---|---|---|
|
Quality of Life Measured by Participant Completed Questionnaire
Day 120
|
84.7 units on a scale
Interval 6.0 to 100.0
|
55.6 units on a scale
Interval 6.0 to 100.0
|
|
Quality of Life Measured by Participant Completed Questionnaire
Day 180
|
88.9 units on a scale
Interval 56.0 to 100.0
|
63.9 units on a scale
Interval 0.0 to 100.0
|
|
Quality of Life Measured by Participant Completed Questionnaire
Day 0
|
34.7 units on a scale
Interval 3.0 to 67.0
|
22.2 units on a scale
Interval 3.0 to 78.0
|
|
Quality of Life Measured by Participant Completed Questionnaire
Day 60
|
73.6 units on a scale
Interval 17.0 to 100.0
|
44.4 units on a scale
Interval 6.0 to 94.0
|
SECONDARY outcome
Timeframe: Baseline, Day 60, Day 120, Day 180Population: One active participant and one placebo participant withdrew after Baseline assessment and no data was provided for the analysis of this endpoint. The overall number of participants analyzed differs from the total number of study participants because the data was either incomplete and/or missing.
This was an exploratory assessment only to analyze whether afamelanotide-induced change in sun exposure would result in a reduction of protoporphyrin IX. The changes of the Total Protoporphyrin IX Level (μg/dL) from Screening Visit (ITT Population) were measured between the two groups. The Protoporphyrin IX level is a laboratory parameter that is measured in specialist labs.
Outcome measures
| Measure |
Afamelanotide
n=38 Participants
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
Placebo
n=37 Participants
Placebo: One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
|---|---|---|
|
Change of Total Protoporphyrin IX Level in Participants
Day 60
|
-471.3 mcg/dL
Standard Deviation 505.4
|
-628.5 mcg/dL
Standard Deviation 837.5
|
|
Change of Total Protoporphyrin IX Level in Participants
Day 120
|
-511.8 mcg/dL
Standard Deviation 595.3
|
-619.9 mcg/dL
Standard Deviation 1022.3
|
|
Change of Total Protoporphyrin IX Level in Participants
Day 180
|
-92.7 mcg/dL
Standard Deviation 549.1
|
-369.2 mcg/dL
Standard Deviation 1265.6
|
SECONDARY outcome
Timeframe: Daily for 6 monthsPopulation: One active participant and one placebo participant withdrew after Baseline assessment and no data was provided for the analysis of this endpoint. The overall number of participants analyzed differs from the total number of study participants because the data was either incomplete and/or missing.
The number of participants who experienced phototoxic reactions with Likert severity scores ≥ 4 and severity scores ≥7 were recorded. A derived endpoint was used. The number of participants who reported at least one phototoxic reaction with a Likert severity score of ≥ 4 was recorded. For severity scores ≥ 7, the number of patients who reported at least one phototoxic reaction with a Likert severity score of ≥ 7 was recorded. The 11-point Likert pain scale ranges from minimum of 0 to maximum of 10. The 11-point Likert pain scale with a value of 0 represents no pain and 10 represents worst imaginable pain.
Outcome measures
| Measure |
Afamelanotide
n=38 Participants
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
Placebo
n=37 Participants
Placebo: One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
|---|---|---|
|
Number of Participants With Phototoxic Reactions With Likert Severity Scores ≥ 4 and ≥ 7
Severity Likert score of ≥ 4
|
26 Count of Participants
|
24 Count of Participants
|
|
Number of Participants With Phototoxic Reactions With Likert Severity Scores ≥ 4 and ≥ 7
Severity Likert score of ≥ 7
|
7 Count of Participants
|
14 Count of Participants
|
SECONDARY outcome
Timeframe: Daily for 6 monthsPopulation: One active participant and one placebo participant withdrew after Baseline assessment and no data was provided for the analysis of this endpoint. The overall number of participants analyzed differs from the total number of study participants because the data was either incomplete and/or missing.
The days on which the participant experienced pain as a result of phototoxic reactions (caused by exposure to natural light) was recorded in a study diary. On each day such a reaction occurred, the participant scored the level of pain using an 11-point Likert pain scale, with minimum of 0 and maximum of 10. The 11-point Likert pain scale with a value of 0 represents no pain and 10 represents worst imaginable pain. The number of phototoxic reactions was determined by counting the number of episodes on which participants report a 11-point Likert scale score of 4 or more for one or more consecutive days.
Outcome measures
| Measure |
Afamelanotide
n=38 Participants
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
Placebo
n=37 Participants
Placebo: One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
|---|---|---|
|
Number of Phototoxic Reactions Experienced by Participants
|
2.0 Episodes
Interval 0.0 to 25.0
|
1.0 Episodes
Interval 0.0 to 13.0
|
SECONDARY outcome
Timeframe: Daily for 6 months.Population: One active participant and one placebo participant withdrew after Baseline assessment and no data was provided for the analysis of this endpoint. The overall number of participants analyzed differs from the total number of study participants because the data was either incomplete and/or missing.
The days on which the participant experienced pain as a result of phototoxic reactions (caused by exposure to natural light) was recorded in a study diary. On each day such a reaction occurred, the participant scored the level of pain using an 11-point Likert pain scale, with minimum of 0 and maximum of 10. The 11-point Likert Pain scale with a value of 0 represents no pain and 10 represents worst imaginable pain. The total severity of phototoxic reactions was determined by the sum of daily 11-point Likert scale scores that occurred during phototoxic reactions. The overall sum of the severity per participant over the entire study was analyzed. The theoretical minimum score is 0 and the maximum possible score is 1800.
Outcome measures
| Measure |
Afamelanotide
n=38 Participants
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
Placebo
n=37 Participants
Placebo: One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
|---|---|---|
|
Total Severity of Phototoxic Reactions Experienced by Participants Over the Entire Study
|
27.9 units on a scale
Standard Deviation 43.1
|
37.2 units on a scale
Standard Deviation 102.6
|
Adverse Events
Afamelanotide
Placebo
Serious adverse events
| Measure |
Afamelanotide
n=39 participants at risk
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
Placebo
n=38 participants at risk
Placebo: One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
|---|---|---|
|
Gastrointestinal disorders
CRAMPY ABDOMINAL PAIN
|
2.6%
1/39 • 6 months (180 days)
|
0.00%
0/38 • 6 months (180 days)
|
|
Nervous system disorders
DIZZINESS
|
0.00%
0/39 • 6 months (180 days)
|
2.6%
1/38 • 6 months (180 days)
|
|
Cardiac disorders
Low Pulse Rate
|
0.00%
0/39 • 6 months (180 days)
|
2.6%
1/38 • 6 months (180 days)
|
|
Gastrointestinal disorders
RECURRENT RECTAL BLEEDING
|
2.6%
1/39 • 6 months (180 days)
|
0.00%
0/38 • 6 months (180 days)
|
Other adverse events
| Measure |
Afamelanotide
n=39 participants at risk
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
Placebo
n=38 participants at risk
Placebo: One placebo subcutaneous implant every 2 months for 6 months. (3 implants in total)
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
20.5%
8/39 • 6 months (180 days)
|
5.3%
2/38 • 6 months (180 days)
|
|
Gastrointestinal disorders
Abdominal discomfort
|
7.7%
3/39 • 6 months (180 days)
|
5.3%
2/38 • 6 months (180 days)
|
|
General disorders
Fatigue
|
7.7%
3/39 • 6 months (180 days)
|
2.6%
1/38 • 6 months (180 days)
|
|
General disorders
Implant Site Pain
|
2.6%
1/39 • 6 months (180 days)
|
13.2%
5/38 • 6 months (180 days)
|
|
General disorders
Pyrexia
|
7.7%
3/39 • 6 months (180 days)
|
2.6%
1/38 • 6 months (180 days)
|
|
Infections and infestations
Nasopharyngitis
|
17.9%
7/39 • 6 months (180 days)
|
5.3%
2/38 • 6 months (180 days)
|
|
Infections and infestations
Sinusitis
|
2.6%
1/39 • 6 months (180 days)
|
7.9%
3/38 • 6 months (180 days)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.7%
3/39 • 6 months (180 days)
|
10.5%
4/38 • 6 months (180 days)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.7%
3/39 • 6 months (180 days)
|
13.2%
5/38 • 6 months (180 days)
|
|
Nervous system disorders
Headache
|
12.8%
5/39 • 6 months (180 days)
|
26.3%
10/38 • 6 months (180 days)
|
Additional Information
Dr. Dennis Wright, Acting Chief Scientific Officer
Clinuvel Pharmaceuticals Limited
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place