Phase 1
N=11
Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Effect of GSK2646264 in Cutaneous Lupus Erythematosus Subjects
Lupus Erythematosus, Cutaneous
Bottom Line
View on ClinicalTrials.gov: NCT02927457 ↗Enrolled (actual)
11
Serious AEs
9.1%
Results posted
Jul 2019
Primary outcome: Primary: Number of Participants With Emergent Chemistry Results by Potential Clinical Importance (PCI) Criteria — 0; 11; 0; 10 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- GSK2646264 1% (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Jun 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Emergent Chemistry Results by Potential Clinical Importance (PCI) Criteria |
0; 11; 0; 10; 0; 11 | — |
| PRIMARY Number of Participants With Emergent Hematology Results by PCI Criteria |
10; 0; 10; 0; 11; 0 | — |
| PRIMARY Change From Baseline in Urine Potential of Hydrogen (pH) |
-0.10; -0.35; -0.32 | — |
| PRIMARY Change From Baseline in Urine Specific Gravity |
0.0007; -0.0001; 0.0003 | — |
| PRIMARY Number of Participants With Emergent Vital Sign Results by PCI Criteria |
0; 10; 0; 0; 11; 0 | — |
| PRIMARY Change From Baseline in Electrocardiogram (ECG); HR |
1.633; -0.606 | — |
| PRIMARY Change From Baseline in ECG; PR Interval, QRS Duration, QT Interval and QTcF |
-0.900; 3.424; -0.967; 1.061; -4.467; 4.455 | — |
| PRIMARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
8; 1 | — |
| SECONDARY Change From Baseline in Erythema, Scaling Hyperkeratosis, Edema/Infiltration, Dyspigmentation, Modified Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) Activity Score and Overall RCLASI Modified Score. |
-0.8; -0.8; -0.5; -0.5; 0.0; 0.0 | — |
| SECONDARY Maximum Observed Concentration (Cmax) of GSK2646264 in Participants With Cutaneous Lupus Erythematosus (CLE) |
0.8324 | — |
| SECONDARY Time to Reach Maximum Observed Concentration (Tmax) of GSK2646264 in Participants With CLE |
311.467 | — |
| SECONDARY Mean Fold Change in Messenger Ribonucleic Acid (mRNA) Expression of Interferon (IFN) Signatures in Skin Biopsies |
1.173; -1.464; -1.001; -1.064; 1.055; -1.164 | — |
Summary
This study is designed to examine safety, tolerability, pharmacokinetics, pharmacodynamics and clinical effect of repeat dosing of GSK2646264 in patients with subacute and chronic cutaneous lupus erythematosus (CLE) lesions and in acute CLE like lesions induced by photoprovocation (PV).
Current study is two group study. In Group A, Patients with fewer than two active lesions will be enrolled and exposed to photoprovocation (PV) for 3 consecutive days. Patients that develop PV lesions at any time during this period, as determined by the local investigative team, will receive 1% strength GSK2646264 on 1 lesion and placebo on 1 lesion daily and either 1% strength GSK2646264 or placebo on an area of uninvolved skin, for skin pharmacokinetic (PK) of study drug, for 28 days.
In Group B, Patients that have a minimum of 2 active existing CLE lesions as determined by the investigators will be enrolled into group B and have one lesion treated with 1% GSK2646264 and 1 lesion with placebo.
A completed patient will be defined as a subject who receives at least 25 days of study drug and completes the end of treatment biopsy (at day 28) and assessment. Thereafter patients will be followed for 28 days in Group A only or until complete resolution of induced PV lesions, as determined by the investigator.
Eligibility Criteria
Inclusion Criteria
- Between 18 and 70 years of age inclusive, at the time of signing the informed consent.
- Subject values for the following parameters thyroid-stimulating hormone (TSH), free thyroxine (T4), and free triiodothyronine (T3) within the normal range.
- Subject has confirmed diagnosis of Lupus Erythematosus Tumidus (LET) (group A only), subacute or chronic CLE as determined by the investigators.
- Body weight >= 50 kg and body mass index (BMI) within the range 19.9 - 35 kilogram (kg)/meter square (m^2) (inclusive)
- Male OR Female.
Females: Non-reproductive potential defined as:
- Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion , Hysterectomy, Documented Bilateral Oophorectomy
- Postmenopausal defined as 12 months of spontaneous amenorrhea. In questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 28 days prior to the first dose of study medication and until 12 days after the last dose of study medication and completion of the follow-up visit.
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
- All subjects must be free from scarring or skin markings (e.g. tattoos or piercings) and open wounds on the defined areas of the body that cream will be applied onto or that will be exposed to PV, unless in the opinion of the investigator it will not compromise the subjects' safety and quality of data.
- Able to refrain from exposure to extended and direct sunlight during the study period, from screening until follow up, especially the area that is under treatment during the study.
- Able to refrain from using self-tanning products on the areas on which the study cream will be applied for the duration of the study from screening to follow-up.
- Able to refrain from shaving and waxing the areas on which the study cream will be applied during the duration of the study from screening to follow up.
- Patient stable on either no treatment or on :
- Corticosteroids (= 2xupper limit of normal (ULN);
- Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 450 millisecond (msec), or QTcF > 480 msec in subjects with Bundle Branch Block
- History of any past or present benign or malignant skin conditions and disease, unless in the opinion of the investigator it will not compromise the subjects safety and quality of data.
- Subjects with a history of Graves disease
- Subjects with a history of thyroid cancer.
- Unable to refrain from vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half lives (whichever is longer) prior to the screening visit until the completion of the follow-up assessments, unless in the opinion of the Investigator, in consultation with the GlaxoSmithKline (GSK) Medical Monitor if required, the medication will not interfere with the study procedures or compromise subject safety.
- Clinically significant abnormality in the hematological, clinical chemistry, or urinalysis screen, as judged by the investigator after discussion with the medical monitor.
- Subjects who start prohibit
Data sourced from ClinicalTrials.gov (NCT02927457). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.