Clinical Trials List
Protocol NumberPRN1008-012
NCT Number(ClinicalTrials.gov Identfier)NCT03762265
2019-01-23 - 2022-12-30
Phase III
Recruiting3
ICD-10L10.0
Pemphigus vulgaris
ICD-10L10.1
Pemphigus vegetans
ICD-10L10.2
Pemphigus foliaceous
ICD-10L10.3
Brazilian pemphigus [fogo selvagem]
ICD-10L10.4
Pemphigus erythematosus
ICD-10L10.5
Drug-induced pemphigus
ICD-10L10.81
Paraneoplastic pemphigus
ICD-10L10.89
Other pemphigus
ICD-10L10.9
Pemphigus, unspecified
ICD-9694.4
Pemphigus
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial to Evaluate the Efficacy and Safety of Oral BTK Inhibitor PRN1008 in Moderate to Severe Pemphigus
-
Trial Applicant
-
Sponsor
Principia Biopharma Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 黃光永 Division of Dermatology
- CHENG-HAN WU Division of Dermatology
- 呂明錡 Division of Dermatology
- 董建學 Division of Dermatology
- 許寶寶 Division of Dermatology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chih-Chieh Chan Division of Dermatology
- 卓雍哲 Division of Dermatology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Pemphigus
Objectives
Efficacy Objectives
• To evaluate the efficacy of PRN1008 in achieving durable CR on low to zero doses of
oral corticosteroid (CS) and on the timecourse of quantitative disease activity scores.
• To assess the ability of PRN1008 to reduce CS exposure and the adverse effects of CS
• To evaluate the time to specified clinical endpoints
• To assesss the longer term durability of CR
Safety Objectives
• To evaluate the safety of PRN1008
• To evaluate differences in potentially CS-related adverse events
PK/PD Objectives
• To evaluate the population pharmacokinetics (PK) of PRN1008
• To evaluate pharmacodynamic (PD) effects of PRN1008 on anti-desmoglein (anti-dsg)
autoantibody titers (anti-dsg1 and anti-dsg3)
Exploratory Objectives
• To examine the effects of PRN1008, if any, of the baseline covariates on PK and/or
PD, and the relationship between PK, PD, and efficacy
• To examine the effect of PRN1008 on the costs of hospitalizations, outpatient medical
visits, adverse events, concomitant medication use and other relevant health economic
outcomes
• To examine the temporal relationship of change from baseline in Pemphigus Disease
Area Index (PDAI) total activity score and quality of life and health economic
measures
Test Drug
PRN1008
Active Ingredient
PRN1008
Dosage Form
Oral
Dosage
400
Endpoints
Primary Efficacy Endpoint
The proportion of patients who are in CR from Week ≤ 29 to Week 37 with a CS dose of ≤ 5
mg/day
Key Secondary Efficacy Endpoints
• Cumulative CS dose over first 36 weeks (to Week 37)
• Time to the beginning of the CR event used to define success for patients reaching the
primary endpoint
• Proportion of patients with CR from Week ≤ 29 to Week 37 with a CS dose of
≤ 10 mg/day
The proportion of patients who are in CR from Week ≤ 29 to Week 37 with a CS dose of ≤ 5
mg/day
Key Secondary Efficacy Endpoints
• Cumulative CS dose over first 36 weeks (to Week 37)
• Time to the beginning of the CR event used to define success for patients reaching the
primary endpoint
• Proportion of patients with CR from Week ≤ 29 to Week 37 with a CS dose of
≤ 10 mg/day
Inclution Criteria
1. Male or female patients, aged 18 to 80 years old with moderate to severe, newly
diagnosed or relapsing PV or PF, with a clinical presentation and histopathology
consistent with PV or PF.
2. Positive circulating anti-dsg1 or 3 autoantibody titer
3. PDAI score of at least 9 points for relapsing patients (diagnosed > 6 months prior to
Screening) or at least 15 points for newly diagnosed patients (diagnosed ≤ 6 months
prior to Screening)
4. Body mass index (BMI) > 17.5
5. Adequate hematologic, hepatic, and renal function (absolute neutrophil count
≥ 1.5 × 109
/L, hemoglobin (Hgb) > 9 g/dL, platelet count ≥ 100 × 109
/L, aspartate
aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 1.5 × upper limit of
normal (ULN), albumin ≥ 3 g/dL, creatinine ≤ 1.5 × ULN
6. Female patients who are of reproductive potential must agree for the duration of the
study to use an effective means of contraception (e.g., hormonal contraception methods
that inhibit ovulation, intrauterine device, intrauterine hormone-releasing system,
bilateral tubal ligation, vasectomized partner or condoms). Unless surgically sterile,
postmenopausal females should have menopause confirmed by follicle-stimulating
hormone (FSH) testing
7. Able to provide written informed consent and agreeable to the schedule of assessments
diagnosed or relapsing PV or PF, with a clinical presentation and histopathology
consistent with PV or PF.
2. Positive circulating anti-dsg1 or 3 autoantibody titer
3. PDAI score of at least 9 points for relapsing patients (diagnosed > 6 months prior to
Screening) or at least 15 points for newly diagnosed patients (diagnosed ≤ 6 months
prior to Screening)
4. Body mass index (BMI) > 17.5
5. Adequate hematologic, hepatic, and renal function (absolute neutrophil count
≥ 1.5 × 109
/L, hemoglobin (Hgb) > 9 g/dL, platelet count ≥ 100 × 109
/L, aspartate
aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 1.5 × upper limit of
normal (ULN), albumin ≥ 3 g/dL, creatinine ≤ 1.5 × ULN
6. Female patients who are of reproductive potential must agree for the duration of the
study to use an effective means of contraception (e.g., hormonal contraception methods
that inhibit ovulation, intrauterine device, intrauterine hormone-releasing system,
bilateral tubal ligation, vasectomized partner or condoms). Unless surgically sterile,
postmenopausal females should have menopause confirmed by follicle-stimulating
hormone (FSH) testing
7. Able to provide written informed consent and agreeable to the schedule of assessments
Exclusion Criteria
1. Suspected paraneoplastic pemphigus and other forms of pemphigus that are not
pemphigus vulgaris or pemphigus foliaceus
2. Previous use of a Bruton’s tyrosine kinase (BTK) inhibitor
3. Pregnant or lactating women
4. Electrocardiogram (ECG) findings of QT corrected for heart rate (QTc) > 450 msec
(males) or > 470 msec (females), poorly controlled atrial fibrillation (i.e., symptomatic
patients or a ventricular rate above 100 beats/min on ECG), or other clinically
significant abnormalities
5. A history of malignancy of any type, other than surgically excised non-melanoma skin
cancers or in situ cervical cancer within 5 years before Day 1
6. Use of immunologic response modifiers as concomitant medication and with the
following washout periods: A) stop at least 2 weeks prior to Screening:
mycophenolate mofetil, azathioprine, methotrexate, cyclosporine, dapsone, intravenous
immunoglobulin (IVIG), Kinaret (anakinra), Enbrel (etanercept) or any other
immunosuppressant not mentioned in this exclusion criterion; B) 12 weeks prior to
Screening: Remicade (infliximab), Humira (adalimumab), Simponi (golimumab),
Orencia (abatercept), Actemra (tocilizumab), Cimzia (certolizumab), Cosentyx
(secukinumab), plasmapheresis; C) 6 months prior to Screening (or shorter if there is
documented B cell reconstitution for anti-CD20 drugs): antiCD20 drugs such as
rituximab, ofatumumab, other long-acting biologics
7. Use of proton pump inhibitor drugs such as omeprazole and esomeprazole within
3 days (It is acceptable to change patient to H2 receptor blocking drugs prior to Day 1.)
8. Concomitant use of known strong-to-moderate inducers or inhibitors of CYP3A within
3 days or 5 half-lives (whichever is longer) of Day 1 (Appendix 8)
9. Use of CYP3A-sensitive substrate drugs with a narrow therapeutic index within 3 days
or 5 half-lives (whichever is longer) of Day 1 and for the remainder of the trial
including, but not limited to alfentanil, astemizole, cisapride, cyclosporine,
dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus,
or terfenadine
10. Has received any investigational drug (or is currently using an investigational device)
within the 30 days before Day 1, or at least 5 times the respective elimination half-life
time (whichever is longer)
11. History of drug abuse within the previous 12 months
12. Alcoholism or excessive alcohol use, defined as regular consumption of more than
approximately 3 standard drinks per day
13. Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant
bowel resection that would preclude adequate PRN1008/placebo absorption
14. Donation of a unit or more of blood or blood products within 4 weeks prior to Day 1
15. History of solid organ transplant
16. Positive at Screening for human immunodeficiency virus (HIV), hepatitis B (surface
and core antibodies unrelated to vaccination, surface antigen), or hepatitis C (anti-HCV
antibody confirmed with Hep C RNA)
17. Positive interferon-gamma release assay (IGRA) (e.g., QuantiFERON®-TB Gold or
T-spot TB® Test) at Screening. Unless, all of the following 3 conditions are true:
a. Chest X-ray does not show evidence suggestive of active tuberculosis (TB)
disease
b. There are no clinical signs and symptoms of pulmonary and/or extra-pulmonary
TB disease
c. Documented receipt of a course of prophylactic TB treatment of at least 6
months
18. History of serious infections requiring intravenous therapy with the potential for
recurrence
19. Live vaccine within 28 days prior to Day 1 or plan to receive one during the trial
20. Any other clinically significant disease, condition, or medical history that, in the
opinion of the Investigator, would interfere with patient safety, trial evaluations, and/or
trial procedures
pemphigus vulgaris or pemphigus foliaceus
2. Previous use of a Bruton’s tyrosine kinase (BTK) inhibitor
3. Pregnant or lactating women
4. Electrocardiogram (ECG) findings of QT corrected for heart rate (QTc) > 450 msec
(males) or > 470 msec (females), poorly controlled atrial fibrillation (i.e., symptomatic
patients or a ventricular rate above 100 beats/min on ECG), or other clinically
significant abnormalities
5. A history of malignancy of any type, other than surgically excised non-melanoma skin
cancers or in situ cervical cancer within 5 years before Day 1
6. Use of immunologic response modifiers as concomitant medication and with the
following washout periods: A) stop at least 2 weeks prior to Screening:
mycophenolate mofetil, azathioprine, methotrexate, cyclosporine, dapsone, intravenous
immunoglobulin (IVIG), Kinaret (anakinra), Enbrel (etanercept) or any other
immunosuppressant not mentioned in this exclusion criterion; B) 12 weeks prior to
Screening: Remicade (infliximab), Humira (adalimumab), Simponi (golimumab),
Orencia (abatercept), Actemra (tocilizumab), Cimzia (certolizumab), Cosentyx
(secukinumab), plasmapheresis; C) 6 months prior to Screening (or shorter if there is
documented B cell reconstitution for anti-CD20 drugs): antiCD20 drugs such as
rituximab, ofatumumab, other long-acting biologics
7. Use of proton pump inhibitor drugs such as omeprazole and esomeprazole within
3 days (It is acceptable to change patient to H2 receptor blocking drugs prior to Day 1.)
8. Concomitant use of known strong-to-moderate inducers or inhibitors of CYP3A within
3 days or 5 half-lives (whichever is longer) of Day 1 (Appendix 8)
9. Use of CYP3A-sensitive substrate drugs with a narrow therapeutic index within 3 days
or 5 half-lives (whichever is longer) of Day 1 and for the remainder of the trial
including, but not limited to alfentanil, astemizole, cisapride, cyclosporine,
dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus,
or terfenadine
10. Has received any investigational drug (or is currently using an investigational device)
within the 30 days before Day 1, or at least 5 times the respective elimination half-life
time (whichever is longer)
11. History of drug abuse within the previous 12 months
12. Alcoholism or excessive alcohol use, defined as regular consumption of more than
approximately 3 standard drinks per day
13. Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant
bowel resection that would preclude adequate PRN1008/placebo absorption
14. Donation of a unit or more of blood or blood products within 4 weeks prior to Day 1
15. History of solid organ transplant
16. Positive at Screening for human immunodeficiency virus (HIV), hepatitis B (surface
and core antibodies unrelated to vaccination, surface antigen), or hepatitis C (anti-HCV
antibody confirmed with Hep C RNA)
17. Positive interferon-gamma release assay (IGRA) (e.g., QuantiFERON®-TB Gold or
T-spot TB® Test) at Screening. Unless, all of the following 3 conditions are true:
a. Chest X-ray does not show evidence suggestive of active tuberculosis (TB)
disease
b. There are no clinical signs and symptoms of pulmonary and/or extra-pulmonary
TB disease
c. Documented receipt of a course of prophylactic TB treatment of at least 6
months
18. History of serious infections requiring intravenous therapy with the potential for
recurrence
19. Live vaccine within 28 days prior to Day 1 or plan to receive one during the trial
20. Any other clinically significant disease, condition, or medical history that, in the
opinion of the Investigator, would interfere with patient safety, trial evaluations, and/or
trial procedures
The Estimated Number of Participants
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Taiwan
20 participants
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Global
120 participants
