Trial Outcomes & Findings for Open-label Study of Tofacitinib for Moderate to Severe Skin Involvement in Young Adults With Lupus (NCT NCT03288324)
NCT ID: NCT03288324
Last Updated: 2024-07-30
Results Overview
Apparent total clearance of the drug from plasma after oral administration
COMPLETED
PHASE1/PHASE2
13 participants
Day 5
2024-07-30
Participant Flow
Participant milestones
| Measure |
Cohort 1 & Cohort 2
Tofacitinib: Tofacitinib 5 mg twice daily
|
|---|---|
|
Overall Study
STARTED
|
12
|
|
Overall Study
COMPLETED
|
11
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Open-label Study of Tofacitinib for Moderate to Severe Skin Involvement in Young Adults With Lupus
Baseline characteristics by cohort
| Measure |
Cohort 1 & Cohort 2
n=11 Participants
Tofacitinib: Tofacitinib 5 mg twice daily
Comparison was not planned for Cohort 1 vs Cohort 2. Cohort 1 received pk analysis. Since only 1 subject was enrolled in cohort 2 the study team is completing analysis with the cohorts combined except for those indicated cohort 1 only in the protocol
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
11 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
21.04 years
STANDARD_DEVIATION 5.89 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
11 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 5Population: Tofacitinib PK was collected from in total of 8 patients, PK parameters were generated for N=7 patients. The PK data for one patient was not used when generating the PK parameters and descriptive summaries due to a dosing event error.
Apparent total clearance of the drug from plasma after oral administration
Outcome measures
| Measure |
Cohort 1
n=7 Participants
Tofacitinib: Tofacitinib 5 mg twice daily
|
|---|---|
|
Oral Clearance (CL/F) (Cohort 1 Only)
|
28.4 (L/hr)
Geometric Coefficient of Variation 23.5
|
SECONDARY outcome
Timeframe: weeks 4, 8 and 24 compared to baseline.Proportion of subjects who achieve a skin response per the validated CLASI The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score consists of two scores. The first summarizes the activity of the disease while the second is a measure of the damage done by the disease. The Activity Score range is 0-70 with the maximum score (70) indicating the worst outcome. The Damage Score range is 0-80 with the maximum score (80) indicating the worst outcome.
Outcome measures
| Measure |
Cohort 1
n=11 Participants
Tofacitinib: Tofacitinib 5 mg twice daily
|
|---|---|
|
Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score
Baseline
|
16.55 score on a scale
Standard Deviation 8.03
|
|
Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score
Week 4
|
10.91 score on a scale
Standard Deviation 8.4
|
|
Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score
Week 8
|
8.64 score on a scale
Standard Deviation 7.8
|
|
Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score
Week 24
|
8.82 score on a scale
Standard Deviation 7.9
|
SECONDARY outcome
Timeframe: Day 5Area under the plasma concentration-time curve linear scale Median Concentration (ng/mL) per nominal time 0-8 hours.
Outcome measures
| Measure |
Cohort 1
n=7 Participants
Tofacitinib: Tofacitinib 5 mg twice daily
|
|---|---|
|
AUCt (Cohort 1 Only)
|
176 (ng.hr/mL)
Geometric Coefficient of Variation 23.5
|
SECONDARY outcome
Timeframe: Day 5Population: Tofacitinib PK was collected from in total of 8 patients, PK parameters were generated for N=7 patients. The PK data for one patient was not used when generating the PK parameters and descriptive summaries due to a dosing event error.
Maximum (or peak) plasma concentration of Tofacitinib
Outcome measures
| Measure |
Cohort 1
n=7 Participants
Tofacitinib: Tofacitinib 5 mg twice daily
|
|---|---|
|
Cmax (Cohort 1 Only)
|
51.7 (ng/mL)
Geometric Coefficient of Variation 21.6
|
SECONDARY outcome
Timeframe: Day 5Population: Tofacitinib PK was collected from in total of 8 patients, PK parameters were generated for N=7 patients. The PK data for one patient was not used when generating the PK parameters and descriptive summaries due to a dosing event error.
Time to reach maximum (peak) plasma concentration following administration of Tofacitinib
Outcome measures
| Measure |
Cohort 1
n=7 Participants
Tofacitinib: Tofacitinib 5 mg twice daily
|
|---|---|
|
Tmax (Cohort 1 Only)
|
1 hr
Interval 0.5 to 2.0
|
SECONDARY outcome
Timeframe: Day 5Population: Tofacitinib PK was collected from in total of 8 patients, PK parameters were generated for N=7 patients. The PK data for one patient was not used when generating the PK parameters and descriptive summaries due to a dosing event error.
Apparent volume of distribution during terminal phase after non-intravenous administration
Outcome measures
| Measure |
Cohort 1
n=7 Participants
Tofacitinib: Tofacitinib 5 mg twice daily
|
|---|---|
|
Vz/F (Cohort 1 Only)
|
85.2 L
Geometric Coefficient of Variation 25.6
|
SECONDARY outcome
Timeframe: Day 5Population: Tofacitinib PK was collected from in total of 8 patients, PK parameters were generated for N=7 patients. The PK data for one patient was not used when generating the PK parameters and descriptive summaries due to a dosing event error.
half-life of Tofacitinib
Outcome measures
| Measure |
Cohort 1
n=7 Participants
Tofacitinib: Tofacitinib 5 mg twice daily
|
|---|---|
|
Half-life of Tofacitinib (Cohort 1 Only)
|
2.1 hr
Standard Deviation 0.321
|
SECONDARY outcome
Timeframe: 76 weeksRate and severity of adverse events and lab abnormalities
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 76 weeksAssess steroid sparing properties of Tofacitinib by comparing doses to baseline and rate of steroid discontinuation
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 76 weeksMeasure Tofacitinib impact on disease activity
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 76 weeksMeasure Tofacitinib impact on disease activity
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, week 24 and week 76Quality-of-life measure for patients with skin disease
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, week 24 and week 76Quality-of-life measure for patients
Outcome measures
Outcome data not reported
Adverse Events
Cohort 1 and 2
Serious adverse events
| Measure |
Cohort 1 and 2
n=11 participants at risk
Tofacitinib: Tofacitinib 5 mg twice daily
|
|---|---|
|
Infections and infestations
Pelvic inflammatory disease
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Infections and infestations
Appendicitis
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Nervous system disorders
Migraine with aura
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
Other adverse events
| Measure |
Cohort 1 and 2
n=11 participants at risk
Tofacitinib: Tofacitinib 5 mg twice daily
|
|---|---|
|
Gastrointestinal disorders
Abdominal tenderness
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Skin and subcutaneous tissue disorders
Acne
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Infections and infestations
Bronchitis
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Injury, poisoning and procedural complications
Burns second degree
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Infections and infestations
Chlamydial infection
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Eye disorders
Conjunctival haemorrhage
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Psychiatric disorders
Depression
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
18.2%
2/11 • Number of events 2 • 76 weeks
|
|
Renal and urinary disorders
Dysuria
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Infections and infestations
Ear infection
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Infections and infestations
Folliculitis
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Infections and infestations
Fungal infection
|
18.2%
2/11 • Number of events 2 • 76 weeks
|
|
Infections and infestations
Gastroenteritis
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Infections and infestations
Gastrointestinal viral infection
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Nervous system disorders
Headache
|
18.2%
2/11 • Number of events 3 • 76 weeks
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Musculoskeletal and connective tissue disorders
Medial tibial stress syndrome
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Reproductive system and breast disorders
Menorrhagia
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Infections and infestations
Nasopharyngitis
|
18.2%
2/11 • Number of events 4 • 76 weeks
|
|
Gastrointestinal disorders
Nausea
|
27.3%
3/11 • Number of events 3 • 76 weeks
|
|
Infections and infestations
Onychomycosis
|
18.2%
2/11 • Number of events 2 • 76 weeks
|
|
Infections and infestations
Otitis externa
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Infections and infestations
Pelvic inflammatory disease
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Infections and infestations
Sinusitis
|
9.1%
1/11 • Number of events 2 • 76 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
|
18.2%
2/11 • Number of events 2 • 76 weeks
|
|
Infections and infestations
Staphylococcal infection
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Infections and infestations
Streptococcal infection
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Psychiatric disorders
Suicidal ideation
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Nervous system disorders
Syncope
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus
|
18.2%
2/11 • Number of events 2 • 76 weeks
|
|
Ear and labyrinth disorders
Tinnitus
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
27.3%
3/11 • Number of events 4 • 76 weeks
|
|
Infections and infestations
Urinary tract infection
|
18.2%
2/11 • Number of events 2 • 76 weeks
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Infections and infestations
Viral infection
|
9.1%
1/11 • Number of events 1 • 76 weeks
|
|
Infections and infestations
Viral upper respiratory tract infection
|
9.1%
1/11 • Number of events 4 • 76 weeks
|
|
Gastrointestinal disorders
Vomiting
|
18.2%
2/11 • Number of events 9 • 76 weeks
|
Additional Information
Hermine Brunner
Cincinnati Childrens Hospital Medical Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place