Multicenter Study to Assess the Efficacy and Safety of Methyl Aminolevulinate Hydrochloride (MAL) 16.8% Cream (CD06809-41) Versus Vehicle Cream for Actinic Keratosis of the Face

• Sponsor: Galderma R&D (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04085367
• Collaborator: (none)
• Enrollment: 557
• Locations: 60
• Arms: 2
• Actual Duration (Months): 18.2
• Patients Per Site: 9.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

A Randomized, Double-Blind, Vehicle-Controlled, Multicenter Study to Assess the Efficacy and Safety of Methyl aminolevulinate hydrochloride (MAL) 16.8% cream (CD06809-41) versus vehicle cream in the treatment of thin and moderately thick, non-hyperkeratotic, non-pigmented actinic keratosis of the face and scalp when using daylight photodynamic therapy (DL-PDT).

Condition or Disease	Intervention/Treatment	Phase
Actinic Keratoses	Drug: MAL 16.8% cream; Drug: MAL Vehicle Cream	Phase 3

Detailed Description

This was a randomized, double-blind, vehicle-controlled, multicenter, parallel-group study in adult participants with clinically-confirmed mild to moderate AKs on the face and the balding scalp, to be conducted at approximately 60 clinical sites in the United States. Sites were selected to ensure that diverse daylight conditions represented in the study to understand the effects of latitude, elevation, and climate.

Study Design

• Study Type: Interventional
• Actual Enrollment: 557 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Vehicle-Controlled, Multicenter Study to Assess the Efficacy and Safety of Methyl Aminolevulinate Hydrochloride (MAL) 16.8% Cream (CD06809-41) Versus Vehicle Cream in the Treatment of Thin and Moderately Thick, Non-hyperkeratotic, Non-pigmented Actinic Keratosis (AK) of the Face and Scalp When Using Daylight Photodynamic Therapy (DL-PDT)
• Actual Study Start Date: Sep 30, 2019
• Actual Primary Completion Date: Mar 3, 2021
• Actual Study Completion Date: Apr 7, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MAL 16.8% Cream Participants received two treatment session at least 2 weeks apart. Investigator applied a thin layer of methyl aminolevulinate (MAL) hydrochloride 16.8% cream to each lesion during treatment. At 30 minutes after cream application, participants went outside in daylight for 2 hours (Daylight photodynamic therapy [DL-PDT]). After this time, the cream was removed by investigative site personnel by washing the skin with gentle skin cleanser.	Drug: MAL 16.8% cream; Day light photodynamic therapy with MAL 16.8% cream; Other Names: CD06809-41
Placebo Comparator: MAL Vehicle Cream Participants received two treatment session at least 2 weeks apart. Investigator applied a thin layer of vehicle cream to each lesion during treatment. At 30 minutes after cream application, participants went outside in daylight for 2 hours (DL-PDT). After this time, the cream was removed by investigative site personnel by washing the skin with gentle skin cleanser.	Drug: MAL Vehicle Cream; Day light photodynamic therapy with MAL vehicle cream

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Complete Response at Week 12 [Week 12]

   Complete response was defined as clearance of all AK lesion treated, at week 12 after the last Daylight photodynamic therapy (DL-PDT).

Secondary Outcome Measures

1. Percent Change From Baseline in Lesion Complete Response at Week 12 [Baseline, Week 12]

   Lesion complete response was defined as percent reduction from baseline in the number of cleared treated lesions, at 12 weeks after the last DL-PDT treatment. This outcome measure was analyzed as an intra-individual comparison between MAL cream and Vehicle cream.

2. Percentage of Participants With Partial Response at Week 12 [Week 12]

   Participants achieving partial response was defined as participants with 75% or greater reduction from baseline in the number of cleared treated lesions, at 12 weeks after the last DL-PDT treatment, comparing MAL cream with vehicle cream.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants aged ≥ 18 years at the Screening visit.

• Participants had at least 4, but no more than 12, clinically-confirmed thin or moderately thick, non-hyperkeratotic, non-pigmented AKs located on the face (e.g., forehead, cheek, chin), and balding scalp.

• Female Participants of non-childbearing potential.

• Participants fully understood and signed an ICF before any investigational procedure(s) are performed.

Exclusion Criteria:

• Participants with pigmented AK in the treatment areas.

• Female participants who were pregnant, nursing, or planning a pregnancy during the study.

• Participants with a clinical diagnosis of a skin disease other than AK.

• Immunocompromised participants.

• Participants with any condition that may be associated with a risk of poor protocol compliance.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Galderma Investigational Site (Site 8768)	Tucson	Arizona	United States	85718
2	Galderma Investigational Site (Site 8447)	Fort Smith	Arkansas	United States	72916-6103
3	Galderma Investigational Site (Site 8577)	Encinitas	California	United States	92024
4	Galderma Investigational Site (Site 8636)	Fountain Valley	California	United States	92708
5	Galderma Investigational Site (Site 8224)	Fremont	California	United States	94538
6	Galderma Investigational Site (Site 8114)	Fresno	California	United States	93720
7	Galderma Investigational Site (Site 8758)	San Diego	California	United States	92121
8	Galderma Investigational Site (Site 8608)	Santa Monica	California	United States	90404
9	Galderma Investigational Site (Site 8778)	Denver	Colorado	United States	80210
10	Galderma Investigational Site (Site 8440)	Greenwood Village	Colorado	United States	80111
11	Galderma Investigational Site (Site 8479)	Bradenton	Florida	United States	34209
12	Galderma Investigational Site (Site 8770)	Lehigh Acres	Florida	United States	33936
13	Galderma Investigational Site (Site 8656)	Miami	Florida	United States	33137
14	Galderma Investigational Site (Site 8765)	North Miami Beach	Florida	United States	33162
15	Galderma Investigation Site (Site 8769)	Palm Springs	Florida	United States	33461
16	Galderma Investigational Site (Site 8734)	Pembroke Pines	Florida	United States	33028
17	Galderma Investigational Site (Site 8529)	Sanford	Florida	United States	32771
18	Galderma Investigational Site (Site 8126)	West Palm Beach	Florida	United States	33401
19	Galderma Investigational Site (Site 8683)	Atlanta	Georgia	United States	30342-1418
20	Galderma Investigational Site (Site 8860)	Atlanta	Georgia	United States	30342
21	Galderma Investigational Site (Site 8667)	Columbus	Georgia	United States	31904
22	Galderma Investigational Site (Site 8755)	Boise	Idaho	United States	83704
23	Galderma Investigational Site (Site 8838)	Darien	Illinois	United States	60561
24	Galderma Investigational Site (Site 8724)	Louisville	Kentucky	United States	40241
25	Galderma Investigational Site (Site 8208)	Beverly	Massachusetts	United States	01915
26	Galderma Investigational Site (Site 8574)	Clarkston	Michigan	United States	48346-3198
27	Galderma Investigation Site (Site 8757)	Saint Joseph	Michigan	United States	49085
28	Galderma Investigational Site (Site 8762)	Edina	Minnesota	United States	55424-1200
29	Galderma Investigational Site (Site 8140)	New Brighton	Minnesota	United States	55112
30	Galderma Investigational Site (Site 8219)	Saint Louis	Missouri	United States	63141
31	Galderma Investigational Site (Site 8869)	Saint Louis	Missouri	United States	63141
32	Galderma Investigational Site (Site 8048)	Omaha	Nebraska	United States	68144
33	Galderma Investigational Site (Site 8420)	Portsmouth	New Hampshire	United States	03801
34	Galderma Investigational Site (Site 8759)	Albuquerque	New Mexico	United States	87102
35	Galderma Investigational Site (Site 8242)	Brooklyn	New York	United States	11203
36	Galderma Investigational Site (Site 8733)	New York	New York	United States	10022
37	Galderma Investigational Site (Site 8279)	New York	New York	United States	10075
38	Galderma Investigational Site (Site 8566)	Charlotte	North Carolina	United States	28277
39	Galderma Investigational Site (Site 8726)	Wilmington	North Carolina	United States	28405-3176
40	Galderma Investigational Site (Site 8595)	Dublin	Ohio	United States	43016
41	Galderma Investiational Site (Site 8212)	Portland	Oregon	United States	97210-2996
42	Galderma Investigational Site (Site 8255)	Philadelphia	Pennsylvania	United States	19103
43	Galderma Investigational Site (Site 8721)	Pittsburgh	Pennsylvania	United States	15213
44	Galderma Investigational Site (Site 8754)	Sugarloaf	Pennsylvania	United States	18249
45	Galderma Investigational Site (Site 8777)	Charleston	South Carolina	United States	29407
46	Galderma Investigational Site (Site 8207)	Nashville	Tennessee	United States	37215
47	Galderma Investigational Site (Site 8076)	Austin	Texas	United States	78759
48	Galderma Investigational Site (Site 8139)	College Station	Texas	United States	77845
49	Galderma Investigational Site (Site 8664)	Frisco	Texas	United States	75034
50	Galderma Investigational Site (Site # 8576)	Houston	Texas	United States	77056
51	Galderma Investigational Site (Site 8546)	Pflugerville	Texas	United States	78660-3519
52	Galderma Investigational Site (Site 8776)	Saint George	Utah	United States	84790
53	Galderma Investigational Site (Site 8672)	Salt Lake City	Utah	United States	84117
54	Galderma Investigational Site (Site 8761)	West Jordan	Utah	United States	84101
55	Galderma Investigational Site (Site 8057)	Lynchburg	Virginia	United States	24501
56	Galderma Investigational Site (Site 8779)	Burien	Washington	United States	98168
57	Galderma Investigational Site (Site 8039)	Spokane	Washington	United States	99202
58	Galderma Investigational Site (Site 8760)	Spokane	Washington	United States	99202
59	Galderma Investigational Site (Site 8725)	Morgantown	West Virginia	United States	26505
60	Galderma Investigational Site (Site 8231)	Aibonito		Puerto Rico	00705

Sponsors and Collaborators

• Galderma R&D

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jul 12, 2020
• Statistical Analysis Plan - Apr 6, 2021

More Information

Publications

None provided.

• Responsible Party: Galderma R&D
• ClinicalTrials.gov Identifier: NCT04085367
• Other Study ID Numbers: RD.06.SPR.112199
• First Posted: Sep 11, 2019
• Last Update Posted: Apr 1, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Keratosis, Actinic; Keratosis

Study Results

Participant Flow

Recruitment Details	A total of 557 participants were randomized in 2:1 ratio in two treatment group, MAL 16.8% cream and vehicle cream in study centers in the United States with diverse latitude, altitude, and climate characteristics.

Arm/Group Title	MAL 16.8% Cream	MAL Vehicle Cream
Arm/Group Description	Participants received two treatment session at least 2 weeks apart. Investigator applied a thin layer of methyl aminolevulinate (MAL) hydrochloride 16.8% cream to each lesion during treatment. At 30 minutes after cream application, participants went outside in daylight for 2 hours (Daylight photodynamic therapy [DL-PDT]). After this time, the cream was removed by investigative site personnel by washing the skin with gentle skin cleanser.	Participants received two treatment session at least 2 weeks apart. Investigator applied a thin layer of vehicle cream to each lesion during treatment. At 30 minutes after cream application, participants went outside in daylight for 2 hours (DL-PDT). After this time, the cream was removed by investigative site personnel by washing the skin with gentle skin cleanser.
Period Title: Overall Study
STARTED	364	193
COMPLETED	344	185
NOT COMPLETED	20	8

Baseline Characteristics

Arm/Group Title	MAL 16.8% Cream	MAL Vehicle Cream	Total
Arm/Group Description	Participants received two treatment session at least 2 weeks apart. Investigator applied a thin layer of methyl aminolevulinate (MAL) hydrochloride 16.8% cream to each lesion during treatment. At 30 minutes after cream application, participants went outside in daylight for 2 hours (Daylight photodynamic therapy [DL-PDT]). After this time, the cream was removed by investigative site personnel by washing the skin with gentle skin cleanser.	Participants received two treatment session at least 2 weeks apart. Investigator applied a thin layer of vehicle cream to each lesion during treatment. At 30 minutes after cream application, participants went outside in daylight for 2 hours (DL-PDT). After this time, the cream was removed by investigative site personnel by washing the skin with gentle skin cleanser.	Total of all reporting groups
Overall Participants	364	193	557
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.2 (8.75)	68.9 (9.00)	69.1 (8.83)
Sex: Female, Male (Count of Participants)
Female	98 26.9%	61 31.6%	159 28.5%
Male	266 73.1%	132 68.4%	398 71.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	33 9.1%	15 7.8%	48 8.6%
Not Hispanic or Latino	327 89.8%	177 91.7%	504 90.5%
Unknown or Not Reported	4 1.1%	1 0.5%	5 0.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 0.3%	0 0%	1 0.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 0.5%	0 0%	2 0.4%
White	359 98.6%	192 99.5%	551 98.9%
More than one race	1 0.3%	1 0.5%	2 0.4%
Unknown or Not Reported	1 0.3%	0 0%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Complete Response at Week 12
Description	Complete response was defined as clearance of all AK lesion treated, at week 12 after the last Daylight photodynamic therapy (DL-PDT).
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

ITT analysis population included all participants randomized in the study.

Arm/Group Title	MAL 16.8% Cream	MAL Vehicle Cream
Arm/Group Description	Participants received two treatment session at least 2 weeks apart. Investigator applied a thin layer of methyl aminolevulinate (MAL) hydrochloride 16.8% cream to each lesion. At 30 minutes after cream application, participants went outside in daylight for 2 hours (Daylight photodynamic therapy [DL-PDT]). After this time, the cream was removed by investigative site personnel by washing the skin with gentle skin cleanser.	Participants received two treatment session at least 2 weeks apart. Investigator applied a thin layer of vehicle cream to each lesion. At 30 minutes after cream application, participants went outside in daylight for 2 hours (DL-PDT). After this time, the cream was removed by investigative site personnel by washing the skin with gentle skin cleanser.
Measure Participants	364	193
Number [percentage of participants]	25.3 7%	23.0 11.9%

2. Secondary Outcome

Title	Percent Change From Baseline in Lesion Complete Response at Week 12
Description	Lesion complete response was defined as percent reduction from baseline in the number of cleared treated lesions, at 12 weeks after the last DL-PDT treatment. This outcome measure was analyzed as an intra-individual comparison between MAL cream and Vehicle cream.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

ITT analysis population included all participants randomized in the study.

Arm/Group Title	MAL 16.8% Cream	MAL Vehicle Cream
Arm/Group Description	Participants received two treatment session at least 2 weeks apart. Investigator applied a thin layer of methyl aminolevulinate (MAL) hydrochloride 16.8% cream to each lesion. At 30 minutes after cream application, participants went outside in daylight for 2 hours (Daylight photodynamic therapy [DL-PDT]). After this time, the cream was removed by investigative site personnel by washing the skin with gentle skin cleanser.	Participants received two treatment session at least 2 weeks apart. Investigator applied a thin layer of vehicle cream to each lesion. At 30 minutes after cream application, participants went outside in daylight for 2 hours (DL-PDT). After this time, the cream was removed by investigative site personnel by washing the skin with gentle skin cleanser.
Measure Participants	364	193
Mean (Standard Error) [percent change]	-61.1 (1.79)	-49.4 (2.45)

3. Secondary Outcome

Title	Percentage of Participants With Partial Response at Week 12
Description	Participants achieving partial response was defined as participants with 75% or greater reduction from baseline in the number of cleared treated lesions, at 12 weeks after the last DL-PDT treatment, comparing MAL cream with vehicle cream.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

ITT analysis population included all participants randomized in the study.

Arm/Group Title	MAL 16.8% Cream	MAL Vehicle Cream
Arm/Group Description	Participants received two treatment session at least 2 weeks apart. Investigator applied a thin layer of methyl aminolevulinate (MAL) hydrochloride 16.8% cream to each lesion. At 30 minutes after cream application, participants went outside in daylight for 2 hours (Daylight photodynamic therapy [DL-PDT]). After this time, the cream was removed by investigative site personnel by washing the skin with gentle skin cleanser.	Participants received two treatment session at least 2 weeks apart. Investigator applied a thin layer of vehicle cream to each lesion. At 30 minutes after cream application, participants went outside in daylight for 2 hours (DL-PDT). After this time, the cream was removed by investigative site personnel by washing the skin with gentle skin cleanser.
Measure Participants	364	193
Number [percentage of participants]	48.2 13.2%	35.1 18.2%

Adverse Events

Time Frame	Baseline up to Week 14
Adverse Event Reporting Description	Safety population consisted of all randomized participants who received at least 1 application of study drug.
Arm/Group Title	MAL 16.8% Cream		MAL Vehicle Cream
Arm/Group Description	Participants received two treatment session at least 2 weeks apart. Investigator was to apply a thin layer of methyl aminolevulinate (MAL) hydrochloride 16.8% cream to each lesion during treatment. At 30 minutes after cream application, participants were to go outside in daylight for 2 hours. After this time, the cream was to be removed by investigative site personnel by washing the skin with gentle skin cleanser.		Participants received two treatment session at least 2 weeks apart. Investigator was to apply a thin layer of vehicle cream to each lesion during treatment. At 30 minutes after cream application, participants were to go outside in daylight for 2 hours. After this time, the cream was to be removed by investigative site personnel by washing the skin with gentle skin cleanser.
All Cause Mortality
	MAL 16.8% Cream		MAL Vehicle Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/364 (0%)		0/193 (0%)
Serious Adverse Events
	MAL 16.8% Cream		MAL Vehicle Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/364 (1.4%)		1/193 (0.5%)
Cardiac disorders
Bradycardia	1/364 (0.3%)		0/193 (0%)
Infections and infestations
Streptococcal endocarditis	1/364 (0.3%)		0/193 (0%)
Injury, poisoning and procedural complications
Back injury	1/364 (0.3%)		0/193 (0%)
Hip fracture	1/364 (0.3%)		1/193 (0.5%)
Metabolism and nutrition disorders
Hyperkalaemia	1/364 (0.3%)		0/193 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/364 (0.3%)		0/193 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma metastatic	1/364 (0.3%)		0/193 (0%)
Other (Not Including Serious) Adverse Events
	MAL 16.8% Cream		MAL Vehicle Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	89/364 (24.5%)		41/193 (21.2%)
General disorders
Application site pain	11/364 (3%)		2/193 (1%)
Application site erythema	12/364 (3.3%)		0/193 (0%)
Application site dermatitis	7/364 (1.9%)		1/193 (0.5%)
Application site pruritus	5/364 (1.4%)		3/193 (1.6%)
Injury, poisoning and procedural complications
Post procedural haemorrhage	7/364 (1.9%)		3/193 (1.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	4/364 (1.1%)		4/193 (2.1%)
Skin and subcutaneous tissue disorders
Actinic keratosis	62/364 (17%)		30/193 (15.5%)
Skin lesion	4/364 (1.1%)		2/193 (1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.