Trial Outcomes & Findings for Phase III Confirmatory Study in Erythropoietic Protoporphyria (NCT NCT01605136)
NCT ID: NCT01605136
Last Updated: 2019-09-19
Results Overview
The amount of direct sunlight exposure between 10:00 and 18:00 hours on days when no pain was experienced (e.g.11-point Likert pain score of 0). Time was recorded in a patient diary 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
PHASE3
93 participants
Daily for 6 months
2019-09-19
Participant Flow
Participant milestones
| Measure |
Afamelanotide
One 16mg subcutaneous implant every 2 months for 6 months.
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months.
|
Placebo
One placebo subcutaneous implant every 2 months for 6 months.
Placebo: One placebo subcutaneous implant every 2 months for 6 months
|
|---|---|---|
|
Study Period
STARTED
|
48
|
45
|
|
Study Period
COMPLETED
|
45
|
42
|
|
Study Period
NOT COMPLETED
|
3
|
3
|
|
Safety Follow-Up Period
STARTED
|
45
|
42
|
|
Safety Follow-Up Period
COMPLETED
|
44
|
40
|
|
Safety Follow-Up Period
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Afamelanotide
One 16mg subcutaneous implant every 2 months for 6 months.
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months.
|
Placebo
One placebo subcutaneous implant every 2 months for 6 months.
Placebo: One placebo subcutaneous implant every 2 months for 6 months
|
|---|---|---|
|
Study Period
Withdrawal by Subject
|
2
|
0
|
|
Study Period
Physician Decision
|
1
|
1
|
|
Study Period
Lost to Follow-up
|
0
|
2
|
|
Safety Follow-Up Period
Withdrawal by Subject
|
1
|
2
|
Baseline Characteristics
Phase III Confirmatory Study in Erythropoietic Protoporphyria
Baseline characteristics by cohort
| Measure |
Afamelanotide
n=48 Participants
One 16mg subcutaneous implant every 2 months for 6 months.
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months.
|
Placebo
n=45 Participants
One placebo subcutaneous implant every 2 months for 6 months.
Placebo: One placebo subcutaneous implant every 2 months for 6 months
|
Total
n=93 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.5 years
n=5 Participants
|
35 years
n=7 Participants
|
37 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
49 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Daily for 6 monthsPopulation: Number of subjects (ITT population, from Patient Diary Card)
The amount of direct sunlight exposure between 10:00 and 18:00 hours on days when no pain was experienced (e.g.11-point Likert pain score of 0). Time was recorded in a patient diary 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=46 Participants
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months.
|
Placebo
n=43 Participants
Placebo: One placebo subcutaneous implant every 2 months for 6 months
|
|---|---|---|
|
Duration of Direct Sunlight Exposure Between 10:00 and 18:00 Hours on Days When no Pain Was Experienced (Pain Score of 0).
|
69.4 hours
Interval 0.0 to 650.5
|
40.8 hours
Interval 0.25 to 224.0
|
SECONDARY outcome
Timeframe: Daily for 6 monthsPopulation: Number of subjects (ITT population, from Patient Diary Card)
Time in direct sunlight exposure between 10:00 and 18:00 hours on days when no or mild pain was experienced (Likert scores of 0 to 3). 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=46 Participants
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months.
|
Placebo
n=43 Participants
Placebo: One placebo subcutaneous implant every 2 months for 6 months
|
|---|---|---|
|
Combined Sun Exposure and Phototoxic Pain
|
80.0 hours
Interval 0.5 to 825.0
|
51.0 hours
Interval 1.25 to 251.0
|
SECONDARY outcome
Timeframe: Daily for 6 monthsPopulation: Number of subjects (ITT population, from Patient Diary Card)
Duration of direct sunlight exposure between 10:00 and 18:00 hours during the study.
Outcome measures
| Measure |
Afamelanotide
n=46 Participants
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months.
|
Placebo
n=43 Participants
Placebo: One placebo subcutaneous implant every 2 months for 6 months
|
|---|---|---|
|
Sun Exposure
|
83.50 hours
Interval 0.5 to 825.0
|
65.25 hours
Interval 3.5 to 278.5
|
SECONDARY outcome
Timeframe: Day 60, Day 120, and Day 180 or early termination.Population: The number of participants analyzed differs from the overall number of participants analyzed because the data was either incomplete and/or missing. Only data from those who completed the Quality of Life assessments are included at each time point.
The Quality of life of participant is measured using DLQI and EPP QoL. The Dermatology Life Quality Index (DLQI) is a simple practical measure for routine clinical use. The DLQI ranges from 0 (no impact on life) to 30 (significant impact on life) . The Erthropoietic protoporphyria quality of life measure (EPP-QoL) scores range from 0 (worst imaginable QoL) to 100 (best possible QoL).
Outcome measures
| Measure |
Afamelanotide
n=47 Participants
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months.
|
Placebo
n=43 Participants
Placebo: One placebo subcutaneous implant every 2 months for 6 months
|
|---|---|---|
|
Quality of Life Score
DLQI - Day 0 (baseline)
|
10.0 units on a scale
Interval 0.0 to 26.0
|
11.0 units on a scale
Interval 0.0 to 22.0
|
|
Quality of Life Score
DLQI - Day 60
|
2.0 units on a scale
Interval 0.0 to 21.0
|
4.0 units on a scale
Interval 0.0 to 21.0
|
|
Quality of Life Score
DLQI - Day 120
|
0.5 units on a scale
Interval 0.0 to 16.0
|
2.5 units on a scale
Interval 0.0 to 19.0
|
|
Quality of Life Score
DLQI - Day 180/Early Termination
|
1.0 units on a scale
Interval 0.0 to 16.0
|
1.0 units on a scale
Interval 0.0 to 14.0
|
|
Quality of Life Score
EPP QOL - Day 0 (baseline)
|
19.4 units on a scale
Interval 0.0 to 83.0
|
22.2 units on a scale
Interval 3.0 to 81.0
|
|
Quality of Life Score
EPP QOL - Day 60
|
77.8 units on a scale
Interval 0.0 to 100.0
|
55.6 units on a scale
Interval 6.0 to 97.0
|
|
Quality of Life Score
EPP QOL - Day 120
|
81.9 units on a scale
Interval 17.0 to 100.0
|
61.1 units on a scale
Interval 6.0 to 97.0
|
|
Quality of Life Score
EPP QOL - Day 180/Early Termination
|
86.1 units on a scale
Interval 6.0 to 100.0
|
69.4 units on a scale
Interval 11.0 to 100.0
|
SECONDARY outcome
Timeframe: Day 0, Day 30, Day 60, Day 90 and Day 120.A subset of subjects was photoprovoked on the dorsal surface of the hand (predilection place) and lower back and the minimum symptom dose (MSD) determined on Days 0, 30, 60, 90 and 120. The amount of radiation required to provoke the first clinical symptom was recorded.
Outcome measures
| Measure |
Afamelanotide
n=10 Participants
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months.
|
Placebo
n=10 Participants
Placebo: One placebo subcutaneous implant every 2 months for 6 months
|
|---|---|---|
|
Photoprovocation
Day 0: dorsal surface of the hand
|
48.9 J/cm^2
Interval 2.3 to 172.0
|
21.0 J/cm^2
Interval 1.1 to 200.0
|
|
Photoprovocation
Change at Day 30: dorsal surface of the hand
|
197.5 J/cm^2
Interval 6.4 to 291.0
|
75.6 J/cm^2
Interval -42.7 to 292.0
|
|
Photoprovocation
Change at Day 60: dorsal surface of the hand
|
128.3 J/cm^2
Interval -62.8 to 298.0
|
36.3 J/cm^2
Interval -1.5 to 157.0
|
|
Photoprovocation
Change at Day 90: dorsal surface of the hand
|
208.3 J/cm^2
Interval 41.6 to 298.0
|
13.9 J/cm^2
Interval -51.3 to 289.0
|
|
Photoprovocation
Change at Day 120: dorsal surface of the hand
|
162.1 J/cm^2
Interval 22.9 to 291.0
|
1.9 J/cm^2
Interval -54.3 to 289.0
|
|
Photoprovocation
Day 0: lower back
|
32.0 J/cm^2
Interval 2.1 to 157.0
|
24.1 J/cm^2
Interval 3.7 to 300.0
|
|
Photoprovocation
Change at Day 30: lower back
|
237.1 J/cm^2
Interval 9.1 to 285.0
|
44.8 J/cm^2
Interval -103.8 to 294.0
|
|
Photoprovocation
Change at Day 60: lower back
|
50.7 J/cm^2
Interval -56.4 to 285.0
|
4.3 J/cm^2
Interval -210.3 to 124.0
|
|
Photoprovocation
Change at Day 90: lower back
|
227.5 J/cm^2
Interval 96.0 to 298.0
|
-2.4 J/cm^2
Interval -132.6 to 124.0
|
|
Photoprovocation
Change at Day 120: lower back
|
82.5 J/cm^2
Interval 10.0 to 271.0
|
12.1 J/cm^2
Interval -187.4 to 124.0
|
SECONDARY outcome
Timeframe: Daily for 6 monthsThe phototoxicity - phototoxic pain secondary endpoint has been divided into two secondary outcome measures. 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=46 Participants
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months.
|
Placebo
n=43 Participants
Placebo: One placebo subcutaneous implant every 2 months for 6 months
|
|---|---|---|
|
Maximum Severity of Phototoxic Reaction Experienced by Participants
|
4.0 score on a scale
Interval 0.0 to 8.0
|
5.0 score on a scale
Interval 0.0 to 9.0
|
SECONDARY outcome
Timeframe: Daily for 6 monthsThe phototoxicity - phototoxic pain secondary endpoint has been divided into two secondary outcome measures. The number of episodes was the endpoint. 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=46 Participants
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months.
|
Placebo
n=43 Participants
Placebo: One placebo subcutaneous implant every 2 months for 6 months
|
|---|---|---|
|
Total Number Phototoxic Reactions Experienced by Participants
|
4 episodes
Interval 0.0 to 196.0
|
6 episodes
Interval 0.0 to 507.0
|
Adverse Events
Afamelanotide
Placebo
Serious adverse events
| Measure |
Afamelanotide
n=48 participants at risk
One 16mg subcutaneous implant every 2 months for 6 months.
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months.
|
Placebo
n=45 participants at risk
One placebo subcutaneous implant every 2 months for 6 months.
Placebo: One placebo subcutaneous implant every 2 months for 6 months
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
2.1%
1/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
0.00%
0/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
2.1%
1/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
0.00%
0/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma in situ
|
0.00%
0/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
2.2%
1/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
2.2%
1/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
Skin and subcutaneous tissue disorders
Melanocytic naevus
|
2.1%
1/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
0.00%
0/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
Other adverse events
| Measure |
Afamelanotide
n=48 participants at risk
One 16mg subcutaneous implant every 2 months for 6 months.
Afamelanotide: One 16mg subcutaneous implant every 2 months for 6 months.
|
Placebo
n=45 participants at risk
One placebo subcutaneous implant every 2 months for 6 months.
Placebo: One placebo subcutaneous implant every 2 months for 6 months
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
18.8%
9/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
17.8%
8/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
General disorders
Pain
|
8.3%
4/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
8.9%
4/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
Infections and infestations
Nasopharyngitis
|
12.5%
6/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
22.2%
10/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.4%
5/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
4.4%
2/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
Nervous system disorders
Headache
|
39.6%
19/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
28.9%
13/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
Gastrointestinal disorders
Abdominal pain
|
2.1%
1/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
6.7%
3/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
General disorders
Implant site discolouration
|
18.8%
9/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
0.00%
0/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
2.1%
1/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
6.7%
3/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
Gastrointestinal disorders
Diarrhoea
|
4.2%
2/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
6.7%
3/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
Gastrointestinal disorders
Dyspepsia
|
6.2%
3/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
6.7%
3/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
General disorders
Fatigue
|
6.2%
3/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
0.00%
0/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
6.7%
3/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
Infections and infestations
Influenza
|
4.2%
2/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
15.6%
7/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
Infections and infestations
Sinusitis
|
6.2%
3/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
6.7%
3/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
12.5%
6/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
13.3%
6/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.2%
3/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
2.2%
1/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.2%
3/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
2.2%
1/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
|
Nervous system disorders
Migraine
|
6.2%
3/48 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
6.7%
3/45 • Visit 1 (Day 0) - Visit 4 (Day 180)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place