Carcinoma, Basal Cell (BCC)
Conditions
Brief summary
This is a Phase 1, open-label, single-arm, multicenter study to assess the safety and tolerability of BSCT (anti-nf-P2X7) 10% Ointment in subjects with BCC.
Detailed description
The purpose of the trial was to determine the safety and tolerability of BSCT (anti-nf-P2X7) 10% Ointment topically applied twice daily for 28 consecutive days in male and female patients with BCC; and to determine the steady-state pharmacokinetics (PK) of the active pharmaceutical ingredient (total sheep Immunoglobulin G \[IgG\]) when BSCT (anti-nf-P2X7) 10% Ointment is applied twice daily to BCC lesions. This was an open-label, single-arm, multicenter Phase 1 study that enrolled 21 BCC patients.
Interventions
DRUGTreatment with BSCT
The study product BSCT (anti-nf-P2X7) 10% Ointment was anti-nf-P2X7 (highly purified sheep IgG) in an ointment formulation for topical administration. The formulation contained 10% weight by weight of the active pharmaceutical ingredient in an anhydrous ointment base. Fifty (50) to 100 mg of product (an amount the size of a small pea) was applied topically twice a day for 28 days to a 25 cm2 area of skin containing a single BCC lesion. The product was to be applied in the morning and in the evening after washing.
Sponsors
TKL Research, Inc.
Biosceptre
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female adults ≥ 18 years of age; * One primary histologically confirmed BCC lesion, not located on the hand or foot, suitable for surgical excision, with a minimum area of 0.5 cm2 and a maximum diameter of 2.0 cm (histological diagnosis made no more than 4 weeks prior to the Screening visit. * Willing to refrain from using non-approved lotions or creams on the BCC treatment site and surrounding area during the treatment period and from washing the treated area for at least 8 hours following each application of study medication; * Ability to follow study instructions and likely to complete all study requirements; * Written informed consent obtained, including consent for biopsy tissue to be examined and stored by the central dermatopathologist; * Written consent to allow photographs of the BCC lesion to be used as part of the study data; * For females of childbearing potential, a negative pregnancy test at Screening and use of an acceptable form of birth control.
Exclusion criteria
* Pregnant, lactating, or planning pregnancy during the study; * Presence of known or suspected systemic cancer; * Histological evidence of squamous cell carcinoma (SCC) or any tumor other than BCC in the biopsy specimen; * Histological evidence of severe squamous metaplasia, infiltrative, desmoplastic, or micronodular growth patterns in the biopsy specimen; * Evidence of dermatological disease or confounding skin condition within the 25-cm2 treatment area, eg, SCC, actinic keratosis, rosacea, psoriasis, atopic dermatitis, eczema, or xeroderma pigmentosa; * Concurrent disease or treatment that suppresses the immune system; * Chronic medical condition that in the judgment of the investigator would interfere with the performance of the study or would place the patient at undue risk; * Known sensitivity to any of the ingredients in the study medication; * Treatment with systemic chemotherapeutic agents (eg, methotrexate, paclitaxel) within the 6 months prior to the Baseline visit; * Use of systemic retinoids within the 6 months prior to the Baseline visit; * Treatment with systemic immunomodulators or immunosuppressants within the 6 months prior to the Baseline visit; * Use of topical immunomodulators within 2 cm of the target treatment area within the 4 weeks prior to the Baseline visit; * Treatment with topical agents for the treatment of BCC or actinic keratosis within 2 cm of the target treatment area within the 4 weeks prior to the Baseline visit: * Treatment with liquid nitrogen, surgical excision or curettage within 2 cm of the target treatment area during the 4 weeks prior to the Baseline visit; * Clinically significant abnormalities as noted in the screening ECG, physical examination, or laboratory test results; * Evidence of current chronic alcohol or drug abuse which, in the investigator's opinion, might interfere with the subject's adherence to protocol requirements; * Current enrollment in an investigational drug or device study or participation in such a study within 4 weeks of the Baseline visit; * In the investigator's opinion, evidence of unwillingness, or inability to follow the restrictions of the protocol and complete the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | 8 weeks | Adverse events and any changes in physical examinations will be monitored, as described in the Code of Federal Regulations (CFR) Title 21 Part 312. In particular local cutaneous irritation including erythema, peeling, dryness, itching, and burning/ stinging that first occur during the study or represent a worsening from Baseline will be recorded as AEs. |
| Pharmacokinetics - Measure Serum Concentration of Total Sheep IgG Using an ELISA. | 28 days | To determine PK, blood levels of sheep IgG were measured in samples collected at Visit 2 (Baseline), Visit 5, predose at Visit 6 (EOT), and then at 1 h, 2 h, and 4 h after the last dose of study medication. |
| Pharmacokinetics - Measure Subject Antibody Response to the Active Pharmaceutical Ingredient Using an Indirect Fluorescent Immuno Assay. | 8 weeks | The active ingredient of BSCT is sheep IgG which may causes an immunogenic response if it enters the systemic circulation. To monitor this response patient blood samples collected at Screening, Visit 2 (Baseline), Visit 6 (EOT), and at Visit 8 (EOS) was tested for anti-sheep IgG antibodies (indicative of immune response against API). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment With BSCT BSCT (anti-nf-P2X7) 10% Ointment topically applied twice daily for 28 consecutive days | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Treatment With BSCT |
|---|---|
| Age, Continuous | 65.0 years STANDARD_DEVIATION 14.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 21 |
| serious Total, serious adverse events | 1 / 21 |
Outcome results
Primary
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Adverse events and any changes in physical examinations will be monitored, as described in the Code of Federal Regulations (CFR) Title 21 Part 312. In particular local cutaneous irritation including erythema, peeling, dryness, itching, and burning/ stinging that first occur during the study or represent a worsening from Baseline will be recorded as AEs.
Time frame: 8 weeks
Population: All (21 of 21) subjects returned for safety and tolerability assessments at days 3, 8, 15 and 29 post-Baseline. 20 of 21 patients returned for final safety assessments was at 57 days post-Baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment With BSCT | Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | Subjects with any Serious Adverse Events | 1 participants |
| Treatment With BSCT | Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | Subjects with Treatment-emergent Adverse Event(s) | 12 participants |
Primary
Pharmacokinetics - Measure Serum Concentration of Total Sheep IgG Using an ELISA.
To determine PK, blood levels of sheep IgG were measured in samples collected at Visit 2 (Baseline), Visit 5, predose at Visit 6 (EOT), and then at 1 h, 2 h, and 4 h after the last dose of study medication.
Time frame: 28 days
Population: At all timepoints, the serum concentration of sheep IgG was too low to be quantified in most of the subjects. One subject had measurable sheep IgG at 1 hr post dose at Visit 6 (EOT) and 3 other subjects had measurable sheep IgG at predose timepoints. In outcome measure below NA represents readings less than lower limit of quantification.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment With BSCT | Pharmacokinetics - Measure Serum Concentration of Total Sheep IgG Using an ELISA. | Pre-dose - Baseline visit | NA ng/ml |
| Treatment With BSCT | Pharmacokinetics - Measure Serum Concentration of Total Sheep IgG Using an ELISA. | Pre dose - Visit 5 | NA ng/ml |
| Treatment With BSCT | Pharmacokinetics - Measure Serum Concentration of Total Sheep IgG Using an ELISA. | Pre dose - Visit 6 | NA ng/ml |
| Treatment With BSCT | Pharmacokinetics - Measure Serum Concentration of Total Sheep IgG Using an ELISA. | 1 hour post dose - Visit 6 | NA ng/ml |
| Treatment With BSCT | Pharmacokinetics - Measure Serum Concentration of Total Sheep IgG Using an ELISA. | 2 hours post dose - Visit 6 | NA ng/ml |
| Treatment With BSCT | Pharmacokinetics - Measure Serum Concentration of Total Sheep IgG Using an ELISA. | 4 hours post dose - Visit 6 | NA ng/ml |
Primary
Pharmacokinetics - Measure Subject Antibody Response to the Active Pharmaceutical Ingredient Using an Indirect Fluorescent Immuno Assay.
The active ingredient of BSCT is sheep IgG which may causes an immunogenic response if it enters the systemic circulation. To monitor this response patient blood samples collected at Screening, Visit 2 (Baseline), Visit 6 (EOT), and at Visit 8 (EOS) was tested for anti-sheep IgG antibodies (indicative of immune response against API).
Time frame: 8 weeks
Population: Anti sheep IgG antibody titres were measured from 21 subjects at screening and baseline, 20 subjects at Visit 6 (Day 29 EOT) and 19 subjects at Visit 8 (Day 57 follow up). The percentage of patients with detectable anti sheep antibodies is reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment With BSCT | Pharmacokinetics - Measure Subject Antibody Response to the Active Pharmaceutical Ingredient Using an Indirect Fluorescent Immuno Assay. | Subjects with anti sheep IgG at screening | 42.9 percentage of subjects |
| Treatment With BSCT | Pharmacokinetics - Measure Subject Antibody Response to the Active Pharmaceutical Ingredient Using an Indirect Fluorescent Immuno Assay. | Subjects with anti sheep IgG at Baseline | 38.1 percentage of subjects |
| Treatment With BSCT | Pharmacokinetics - Measure Subject Antibody Response to the Active Pharmaceutical Ingredient Using an Indirect Fluorescent Immuno Assay. | Subjects with anti sheep IgG at visit 6 | 50 percentage of subjects |
| Treatment With BSCT | Pharmacokinetics - Measure Subject Antibody Response to the Active Pharmaceutical Ingredient Using an Indirect Fluorescent Immuno Assay. | Subjects with anti sheep IgG at visit 8 | 52.6 percentage of subjects |
Post Hoc
Change in Lesion Size.
BCC lesion area was measured at Baseline and after 28 days treatment. Percantage change in lesion area was caculated.
Time frame: 28 days
Population: Final area of lesion was not recorded for one subject.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment With BSCT | Change in Lesion Size. | -12.86 percentage change in tumour area | Standard Error 5.88 |