A Multi-Center Study to Evaluate the Efficacy and Safety of KX2-391 Ointment 1% on Actinic Keratosis on Face or Scalp (AK004)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03285490 |
|
Recruitment Status :
Completed
First Posted : September 18, 2017
Results First Posted : March 10, 2021
Last Update Posted : March 10, 2021
|
Sponsor:
Almirall, S.A.
Collaborator:
Athenex, Inc.
Information provided by (Responsible Party):
Almirall, S.A.
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Brief Summary:
This Phase III study was designed to evaluate the efficacy and safety of KX2-391 Ointment 1% in adult participants when applied to an area of skin containing 4-8 stable, clinically typical actinic keratosis (AK) lesions on the face or scalp.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Actinic Keratosis | Drug: KX2-391 Ointment 1% Drug: Placebo | Phase 3 |
This study was a double-blinded, multicenter, efficacy, and safety study of KX2-391 ointment administered topically to the face or scalp of participants with AK.
The study consisted of Screening, Treatment, Follow-up, and Recurrence Follow-up Periods. Eligible participants received up to 5 consecutive days of topical treatment. Efficacy (lesion counts) and safety evaluations were performed.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 351 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | This study tested KX2-391 Ointment 1% against a placebo. |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Masking Description: | All Central Vendors and the sponsor were masked. The sponsor was unblind at the end of Day 57. |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3, Double-Blind, Vehicle-Controlled, Randomized, Parallel Group, Multicenter, Efficacy and Safety Study of KX2-391 Ointment 1% in Adult Subjects With Actinic Keratosis on the Face or Scalp |
| Actual Study Start Date : | September 15, 2017 |
| Actual Primary Completion Date : | May 7, 2018 |
| Actual Study Completion Date : | April 24, 2019 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: KX2-391 Ointment 1%
KX2-391 Ointment was applied once daily for 5 consecutive days on the face or scalp.
|
Drug: KX2-391 Ointment 1%
Dose: 1% (250 mg single-use packets); Dosage form: Ointment; Route of administration: Topical |
|
Placebo Comparator: Placebo
The Vehicle Ointment was applied once daily for 5 consecutive days on the face or scalp.
|
Drug: Placebo
Dosage form: Ointment; Route of administration: Topical |
Primary Outcome Measures :
- Percentage of Participants With Complete (100%) Clearance of Actinic Keratosis (AK) Lesions [ Time Frame: Day 57 ]Complete clearance rate was defined as the percentage of participants at Day 57 with no clinically visible AK lesions in the treatment area.
Secondary Outcome Measures :
- Percentage of Participants With Partial Clearance Rate of Actinic Keratosis Lesions at Day 57 [ Time Frame: Day 57 ]Partial clearance rate of AK lesions was defined as the percentage of participants with a greater than or equal to (>=) 75% reduction in the number of AK lesions identified at Baseline (Day 1 predose) in the treatment area.
- Overall Change From Baseline in Actinic Keratosis Lesion Counts at Days 8, 15, 29 and 57 [ Time Frame: Days 8, 15, 29 and 57 ]Overall the change from baseline in lesion count at each visit were summarized and reported using descriptive statistics by treatment location (face or scalp).
- Percentage of Participants With Recurrence of Actinic Keratosis Lesions Who Achieved Complete Clearance at Day 57 [ Time Frame: 3, 6, 9 and 12 months post-Day 57 ]Recurrence rate was estimated based on Kaplan-Meier method, with recurrence define as appearance of any AK lesions in the treatment area, including those recurred or newly identified.
- Number of Participants With Maximal Post Baseline Local Skin Reaction (LSR) [ Time Frame: Day 57 ]Maximal post baseline LSR was defined as the highest grade of any LSR reported at any post baseline visits for a participant. The LSR assessment was an Investigator's (or sub-investigator's) assessment of the following signs on the treatment area: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration. The LSRs were graded on a 4-point scale ranging from 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense).
- Number of Participants With Pigmentation and Scarring in the Treatment Area [ Time Frame: Baseline (Day 1 predose), Days 5, 8, 15, 29 and 57 ]Absence or presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment area were assessed.
- Number of Participants With Adverse Event (AE), Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Events of Special Interests [ Time Frame: Baseline (Day 1 predose) up to Day 57 ]An AE was defined as any untoward medical occurrence in participant which does not necessarily have causal relationship with treatment. An AE was any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of medicinal product, whether or not considered related to medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death; was life threatening; required persistent/significant disability/incapacity; resulted in initial or prolonged in patient hospitalization; was congenital anomaly/birth defect or otherwise considered medically important. TEAEs (serious and non-serious) were defined as either those AEs with onset after first dose or those pre-existing AEs that worsen after first dose. Events of special interest included skin cancers (including basal cell carcinoma, squamous cell carcinoma, melanoma and their location and treatment area), ocular exposure, overdose, and pregnancy.
- Number of Participants With Adverse Events, Serious Adverse Events, Events of Special Interests Within the Treatment Area After Day 57 and up to 12 Months Post-Day 57 [ Time Frame: From Day 57 up to 12-months post-Day 57 ]An AE was defined as any untoward medical occurrence in participant which does not necessarily have causal relationship with treatment. An AE was any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with use of medicinal product, whether or not considered related to medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death; was life threatening; required persistent/significant disability/incapacity; resulted in initial or prolonged in patient hospitalization; was congenital anomaly/birth defect or otherwise considered medically important. Events of special interest included skin cancers (including basal cell carcinoma, squamous cell carcinoma, melanoma and their location and treatment area), ocular exposure, overdose, and pregnancy.
- Number of Participants With Clinically Significant Safety Observations- Hematology, Blood Chemistry, Urinalysis [ Time Frame: From Baseline (Day 1 predose) up to Day 57 ]Assessed laboratory parameters included hematology, blood chemistry and urinalysis. Clinical significance and abnormal observations were determined by the investigator.
- Number of Participants With Clinically Significant Safety Observations- Vital Signs [ Time Frame: From Baseline (Day 1 predose) up to Day 57 ]Vital signs included measurement of pulse rate, systolic and diastolic blood pressure, respiratory rate, and body temperature. Clinical significance was determined by the investigator.
- Number of Participants With Clinically Significant Safety Observations- Physical Examination [ Time Frame: From Baseline (Day 1 predose) up to Day 57 ]A physical examination included weight and height measurements was performed. Clinical significance was determined by the investigator.
- Number of Participants With Clinically Significant Safety Observations- Electrocardiograms (ECGs) [ Time Frame: From Baseline (Day 1 predose) up to Day 57 ]ECG parameters included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals. Clinical significance was determined by the investigator.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria
- Males and females greater than or equal to (>=) 18 years old.
- A defined area on the face or scalp contains 4 to 8 clinically typical, visible, and discrete AK lesions.
- Participants who in the judgment of the Investigator, were in good general health.
- Females were postmenopausal (greater than [>] 45 years of age with at least 12 months of amenorrhea), surgically sterile (by hysterectomy, bilateral oophorectomy, or tubal ligation); or, if of childbearing potential, were using highly effective contraception for at least 30 days or 1 menstrual cycle, whichever was longer, prior to study treatment and agreed to continue to use highly effective contraception for at least 30 days following their last dose of study treatment. Highly effective contraception includes oral hormonal contraceptives, hormonal contraceptive implant, injection or patch, intrauterine device or complete abstinence from sexual intercourse.
- Sexually active males who had not had a vasectomy, and whose partner was reproductively capable, must had agreed to use barrier contraception from Screening through 90 days after their last dose of study treatment.
- All participants must had agreed not to donate sperm or eggs or attempt conception from Screening through 90 days following their last dose of study treatment.
- Willing to avoid excessive sun or ultraviolet exposure.
- Able to comprehend and were willing to sign the informed consent form (ICF).
Exclusion Criteria
- Clinically atypical and/or rapidly changing AK lesions on the treatment area.
-
Location of the selected area is:
- On any location other than the face or scalp.
- Within 5 centimeters (cm) of an incompletely healed wound.
- Within 5 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma (SCC).
- Been previously treated with KX2-391 Ointment.
- Anticipated need for in-patient hospitalization or in-patient surgery from Day 1 to Day 57.
- Treatment with 5-fluorouracil (5-FU), imiquimod, ingenol mebutate, diclofenac, photodynamic therapy, or other treatments for AK within the treatment area or within 2 cm of the treatment area, within 8 weeks prior to the Screening visit.
-
Use of the following therapies and/or medications within 2 weeks prior to the Screening visit:
- Cosmetic or therapeutic procedures (e.g., use of liquid nitrogen, surgical excision, curettage, dermabrasion, medium or greater depth chemical peel, laser resurfacing) within the treatment area or within 2 cm of the selected treatment area.
- Acid-containing therapeutic products (eg, salicylic acid or fruit acids, such as alpha- and beta-hydroxyl acids and glycolic acids), topical retinoids, or light chemical peels within the treatment area or within 2 cm of the selected treatment area.
- Topical salves (non-medicated/non-irritant lotion and cream were acceptable) or topical steroids within the treatment area or within 2 cm of the selected treatment area; artificial tanners within the treatment area or within 5 cm of the selected treatment area.
-
Use of the following therapies and/or medications within 4 weeks prior to the Screening visit:
- Treatment with immunomodulators (eg, azathioprine), cytotoxic drugs (eg, cyclophosphamide, vinblastine, chlorambucil, methotrexate) or interferons/interferon inducers.
- Treatment with systemic medications that suppress the immune system (eg, cyclosporine, prednisone, methotrexate, alefacept, infliximab).
- Use of systemic retinoids (eg, isotretinoin, acitretin, bexarotene) within 6 months prior to the Screening visit.
- A history of sensitivity and/or allergy to any of the ingredients in the study medication.
- A skin disease (e.g., atopic dermatitis, psoriasis, eczema) or condition (e.g., scarring, open wounds) that, in the opinion of the Investigator, might interfere with the study conduct or evaluations, or which exposes the participant to unacceptable risk by study participation.
- Other significant uncontrolled or unstable medical diseases or conditions that, in the opinion of the Investigator, would expose the participant to unacceptable risk by study participation.
- Females who were pregnant or nursing.
- Participated in an investigational drug trial during which an investigational study medication was administered within 30 days or 5 half-lives of the investigational product, whichever was longer, before dosing.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03285490
Locations
Show 30 study locations
Sponsors and Collaborators
Almirall, S.A.
Athenex, Inc.
Investigators
| Study Chair: | Jane Fang, MD | Athenex, Inc. |
Study Documents (Full-Text)
Documents provided by Almirall, S.A.:
Documents provided by Almirall, S.A.:
Study Protocol [PDF] February 18, 2018
Statistical Analysis Plan [PDF] June 4, 2019
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Almirall, S.A. |
| ClinicalTrials.gov Identifier: | NCT03285490 |
| Other Study ID Numbers: |
KX01-AK-004 U1111-1191-8287 ( Other Identifier: UTN ) |
| First Posted: | September 18, 2017 Key Record Dates |
| Results First Posted: | March 10, 2021 |
| Last Update Posted: | March 10, 2021 |
| Last Verified: | February 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Almirall, S.A.:
|
Actinic Keratosis Keratosis Keratosis, Actinic Precancerous Conditions |
Neoplasms Sun Damaged Skin Actinic Keratoses |
Additional relevant MeSH terms:
|
Keratosis, Actinic Keratosis Skin Diseases Precancerous Conditions |
Neoplasms Tirbanibulin Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |