Pemphigus Vulgaris
Conditions
Brief summary
Open-label cohort study in adult patients with newly diagnosed or relapsing pemphigus vulgaris, with intra-patient dose-adjustment based on clinical response and BTK occupancy, and with conventional immunosuppressive rescue treatment, if indicated. The duration of therapy in Part A will be 12 weeks, followed by 12 weeks of follow up. The extension phase, Part B includes 24 weeks of therapy, followed by 4 weeks of follow-up.
Detailed description
Primary Objectives: To evaluate the safety of PRN1008 in patients with pemphigus vulgaris (PV) To evaluate the clinical activity of PRN1008 in patients with PV, per criteria in the European Academy of Dermatology and Venereology (EADV) 2014 Pemphigus S2 Guideline (Hertl et al. 2015) Secondary Objectives To evaluate the pharmacokinetics (PK) and the pharmacodynamics (PD) of multiple doses of PRN1008 in patients with PV To evaluate the relationship of PK and PD to each other and to efficacy and safety in this patient population
Interventions
DRUGPRN1008
Part A dosing was initiated administering 400 mg BID. Intrapatient dose adjustments (reductions and increases) were permitted based upon tolerability and clinical response with the maximum dose allowed up to 600 mg BID for 12 weeks. Part B initial dosing was 400 mg QD for 2 weeks with dose escalation to 400 mg BID at the discretion of the Investigator for the purposes of investigating dose response and identifying the minimal efficacious dose of rilzabrutinib for 24 weeks.
Sponsors
Principia Biopharma, a Sanofi Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Intervention model description
Part A with 12 weeks treatment and 12 weeks follow-up. Part B with 24 weeks treatment and 4 weeks follow-up.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male or female patients, aged 18 to 80 years old, with biopsy-proven, mild-moderate PV (PDAI 8 to 45) in Part A and mild to severe PV in Part B (PDAI 8 to 60) that are either: * newly diagnosed patients (i.e. naïve to an effective induction treatment regimen) for whom an initial period of PRN1008 monotherapy is judged clinically acceptable, or * relapsing patients, for whom an initial period of PRN1008 monotherapy, or combination therapy with any of low dose corticosteroid, ie.0.5 mg/kg of prednis(ol)one per day
Exclusion criteria
* Pregnant or lactating women * A history of malignancy of any type, other than surgically excised non-melanoma skin cancers or in situ cervical cancer within 5 years before the day of dosing * Use of immunologic response modifiers with the following periods prior to Day 1: 1 week: cyclophosphamide; 4 weeks: intravenous immunoglobulin, Kinaret (anakinra) and Enbrel (etanercept); 12 weeks: Remicade (infliximab), Humira (adalimumab), Simponi (golimumab), Orencia (abatacept), Actemra (tocilizumab), Cimzia (certolizumab), Cosentyx (secukinumab), plasmapheresis; 6 months: Rituxan/MabThera (rituximab), ofatumumab, any other anti-CD20 antibody, other long acting biologics * More than 0.5 mg/kg of prednis(ol)one per day (low dose corticosteroids) within the two weeks prior to Day 1 * Use of proton pump inhibitor drugs such as omeprazole and esomeprazole * Has received any investigational drug (or is currently using an investigational device) within the 30 days before receiving the first dose of study medication, or at least 5 times the respective elimination half-life time (whichever is longer) * History of drug abuse within the precious 12 months * Alcoholism or excessive alcohol use, defined as regular consumption of more than approximately 3 standard drinks per day * Refractory nausea and vomiting, malabsorption, external biliary shunt, significant bowel resection that would preclude adequate study drug absorption * History of anorexia nervosa or periods of three months or more of low body weight in the past 5 years * Donation of a unit or more of blood or blood products within 4 weeks prior to Day 1 * History of solid organ transplant * History of epilepsy or other forms of seizures in the last 5 years * Positive for screening for human immunodeficiency virus, hepatitis B (surface and core antibodies unrelated to vaccination), or hepatitis C (anti-HCV antibody confirmed with Hep C RNA) * History of active or latent tuberculosis (TB) infection (must test negative using the QuantiFERON test to be eligible) * History of serious infections requiring intravenous (by catheter that delivers antibiotics into your blood) treatment * Live vaccine within 28 days prior to baseline or plan to receive one during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-emergent Adverse Events | Part A: until 24 weeks and Part B: until 28 weeks | Treatment-emergent adverse events (TEAEs) including clinically significant changes in physical examination, laboratory tests, and vital signs. An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment phase that was defined as the time from the start of study drug up to study completion. |
| Percentage of Participants Who Are Able to Achieve Control of Disease Activity (CDA) Within 4 Weeks of Starting PRN1008 Treatment Without the Need for Doses of Prednisone or Prednisolone >0.5 mg/kg | 4 weeks | CDA was defined as the time at which new lesions cease to form and established lesions begin to heal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Able to Achieve Complete Remission (CR) Without the Need for Doses of Prednisone or Prednisolone of Greater Than 0.5mg/kg | Part A: 12 weeks treatment and Part B: 24 weeks treatment | CR was defined as complete healing of all lesions and the absence of new lesions. |
| Time to Control of Disease Activity (CDA) | Part A: until 24 weeks and Part B: until 28 weeks | CDA was defined as the time at which new lesions cease to form and established lesions begin to heal. Kaplan-Meier estimate median time is reported. |
| Time to End of Consolidation Phase (ECP) | Part A: until 24 weeks and Part B: until 28 weeks | ECP was defined as the time at which no new lesions have developed for minimum of 2 weeks, and approximately 80% of existing lesions have healed. The median time to ECP was based on Kaplan-Meier estimate which considered censoring at end of follow-up for patients who didn't have an event. A +/-3 days window for visits at Week 3 and 5, and +/-7 days window for visits at Week 9, 13, 17, 21, 25. |
| Time to Complete Remission (CR) | Part A: until 24 weeks and Part B: until 28 weeks | CR was defined as complete healing of all lesions and the absence of new lesions. |
| Time to Relapse After PRN1008 Treatment Discontinuation | Part A: until 24 weeks and Part B: until 28 weeks | Relapse was defined as appearance of ≥3 new lesions/month that do not heal spontaneously within 1 week, or by extension of established lesions, in a patient who has achieved disease control. The median time to relapse was based on Kaplan-Meier estimate which considered censoring at end of follow-up for patients who didn't have an event. A +/-3 days window for visits at Week 3 and 5, and +/-7 days window for visits at Week 9, 13, 17, 21, 25. |
| Percentage of Participants Able to Achieve Control of Disease Activity (CDA) Without Corticosteroids Within 4 Weeks | 4 weeks | CDA was defined as the time at which new lesions cease to form and established lesions begin to heal. |
| Percentage Change From Baseline in Pemphigus Disease Area Index (PDAI) Total Activity Scores | Part A: until 24 weeks and Part B: until 28 weeks | The PDAI questionnaire has 2 components including activity and damage. The activity component consists of skin, scalp and mucosa parts, and the damage component consists of skin and scalp parts. The total activity score was used for the summary of PDAI scores. PDAI total activity score = Total skin activity + Total scalp activity + Total mucosa activity. PDAI Total Activity Score ranged from 0 to 250 points representing disease activity (higher scores mean a worse outcome). Negative change in total activity score from baseline indicates improvement in pemphigus activity. |
| Change From Baseline in Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) Total Activity Score | Part A: until 24 weeks and Part B: until 28 weeks | ABSIS Total Activity Score ranged from 0 to 206 points representing disease activity (higher scores mean a worse outcome). Negative change in total activity score from baseline indicates improvement in pemphigus activity. |
| Change From Baseline in Autoimmune Bullous Diseases Quality of Life (ABQOL) | Part A: until 24 weeks and Part B: until 28 weeks | ABQOL score ranged from 0 to 68 points representing disease activity (higher scores mean a worse outcome). |
| Change From Baseline in Treatment of Autoimmune Bullous Diseases Quality of Life (TABQOL) Scores | Part A: until 24 weeks and Part B: until 28 weeks | TABQOL score ranged from 0 to 68 points representing disease activity (higher scores mean a worse outcome). |
| Change From Baseline in Appetite (SNAQ Score) | Part A: until 24 weeks and Part B: until 28 weeks | Simplified Nutritional Appetite Questionnaire (SNAQ) score ranged from 0 to 20 points representing disease activity (higher scores mean a better outcome). |
| Cumulative Corticosteroid Usage | Part A: until 24 weeks and Part B: until 28 weeks | Cumulative corticosteroid usage |
| Percentage of Participants Able to Achieve a Complete Response (CR) Without Corticosteroids | Part A: 12 weeks treatment and Part B: 24 weeks treatment | CR was defined as complete healing of all lesions and the absence of new lesions. |
Countries
Australia, Croatia, France, Greece, Israel
Participant flow
Recruitment details
The study was conducted at 13 centers in 5 countries from 22 January 2016 to 10 January 2020.
Pre-assignment details
A total of 69 patients were screened for the study (52 patients in Part A and 18\* patients in Part B). Of these, 41 unique patients were enrolled in the study (27 patients in Part A and 15\* patients in Part B). \*One patient who completed Part A of the study and later relapsed was enrolled in Part B.
Participants by arm
| Arm | Count |
|---|---|
| Part A Open-label PRN1008, 12 weeks; 12 weeks follow-up | 27 |
| Part B Open-label PRN1008, 24 weeks; 4 weeks follow-up | 15 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part A: 24 Weeks | Adverse Event | 3 | 0 |
| Part B: 28 Weeks | Worsening of pemphigus | 0 | 1 |
Baseline characteristics
| Characteristic | Part A | Part B | Total |
|---|---|---|---|
| Age, Categorical Part A <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Part A >=65 years | 3 Participants | 0 Participants | 3 Participants |
| Age, Categorical Part A Between 18 and 65 years | 24 Participants | 0 Participants | 24 Participants |
| Age, Categorical Part B <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Part B >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Part B Between 18 and 65 years | 0 Participants | 15 Participants | 15 Participants |
| Race (NIH/OMB) Part A American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part A Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Part A Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part A More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part A Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part A Unknown or Not Reported | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Part A White | 22 Participants | 0 Participants | 22 Participants |
| Race (NIH/OMB) Part B American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part B Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Part B Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part B More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part B Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Part B Unknown or Not Reported | 0 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) Part B White | 0 Participants | 8 Participants | 8 Participants |
| Sex: Female, Male Part A Female | 15 Participants | 0 Participants | 15 Participants |
| Sex: Female, Male Part A Male | 12 Participants | 0 Participants | 12 Participants |
| Sex: Female, Male Part B Female | 0 Participants | 7 Participants | 7 Participants |
| Sex: Female, Male Part B Male | 0 Participants | 8 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 15 |
| other Total, other adverse events | 20 / 27 | 13 / 15 |
| serious Total, serious adverse events | 3 / 27 | 0 / 15 |
Outcome results
Primary
Percentage of Participants Who Are Able to Achieve Control of Disease Activity (CDA) Within 4 Weeks of Starting PRN1008 Treatment Without the Need for Doses of Prednisone or Prednisolone >0.5 mg/kg
CDA was defined as the time at which new lesions cease to form and established lesions begin to heal.
Time frame: 4 weeks
Population: Intent-to-Treat (ITT) population: All patients who received at least 1 dose of rilzabrutinib
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A | Percentage of Participants Who Are Able to Achieve Control of Disease Activity (CDA) Within 4 Weeks of Starting PRN1008 Treatment Without the Need for Doses of Prednisone or Prednisolone >0.5 mg/kg | 51.9 percentage of participants |
| Part B | Percentage of Participants Who Are Able to Achieve Control of Disease Activity (CDA) Within 4 Weeks of Starting PRN1008 Treatment Without the Need for Doses of Prednisone or Prednisolone >0.5 mg/kg | 60.0 percentage of participants |
Primary
Percentage of Participants With Treatment-emergent Adverse Events
Treatment-emergent adverse events (TEAEs) including clinically significant changes in physical examination, laboratory tests, and vital signs. An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment phase that was defined as the time from the start of study drug up to study completion.
Time frame: Part A: until 24 weeks and Part B: until 28 weeks
Population: Safety Analysis population: All patients who received at least 1 dose of rilzabrutinib; used for all safety analyses
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A | Percentage of Participants With Treatment-emergent Adverse Events | Any TEAE | 74.1 percentage of participants |
| Part A | Percentage of Participants With Treatment-emergent Adverse Events | Any serious TEAE | 11.1 percentage of participants |
| Part A | Percentage of Participants With Treatment-emergent Adverse Events | Any TEAE leading to treatment discontinuation | 11.1 percentage of participants |
| Part B | Percentage of Participants With Treatment-emergent Adverse Events | Any TEAE | 86.7 percentage of participants |
| Part B | Percentage of Participants With Treatment-emergent Adverse Events | Any serious TEAE | 0 percentage of participants |
| Part B | Percentage of Participants With Treatment-emergent Adverse Events | Any TEAE leading to treatment discontinuation | 0 percentage of participants |
Secondary
Change From Baseline in Appetite (SNAQ Score)
Simplified Nutritional Appetite Questionnaire (SNAQ) score ranged from 0 to 20 points representing disease activity (higher scores mean a better outcome).
Time frame: Part A: until 24 weeks and Part B: until 28 weeks
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Change From Baseline in Appetite (SNAQ Score) | end of treatment | 1.1 units on a scale | Standard Deviation 2.45 |
| Part A | Change From Baseline in Appetite (SNAQ Score) | end of follow-up | 1.0 units on a scale | Standard Deviation 2.84 |
| Part B | Change From Baseline in Appetite (SNAQ Score) | end of treatment | 0.21 units on a scale | Standard Deviation 2.082 |
| Part B | Change From Baseline in Appetite (SNAQ Score) | end of follow-up | 0.50 units on a scale | Standard Deviation 2.103 |
Secondary
Change From Baseline in Autoimmune Bullous Diseases Quality of Life (ABQOL)
ABQOL score ranged from 0 to 68 points representing disease activity (higher scores mean a worse outcome).
Time frame: Part A: until 24 weeks and Part B: until 28 weeks
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Change From Baseline in Autoimmune Bullous Diseases Quality of Life (ABQOL) | end of treatment | -3.7 score on a scale | Standard Deviation 6.96 |
| Part A | Change From Baseline in Autoimmune Bullous Diseases Quality of Life (ABQOL) | end of follow-up | -2.9 score on a scale | Standard Deviation 6.71 |
| Part B | Change From Baseline in Autoimmune Bullous Diseases Quality of Life (ABQOL) | end of treatment | -6.36 score on a scale | Standard Deviation 9.394 |
| Part B | Change From Baseline in Autoimmune Bullous Diseases Quality of Life (ABQOL) | end of follow-up | -3.79 score on a scale | Standard Deviation 9.569 |
Secondary
Change From Baseline in Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) Total Activity Score
ABSIS Total Activity Score ranged from 0 to 206 points representing disease activity (higher scores mean a worse outcome). Negative change in total activity score from baseline indicates improvement in pemphigus activity.
Time frame: Part A: until 24 weeks and Part B: until 28 weeks
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Change From Baseline in Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) Total Activity Score | end of treatment | -8.18 score on a scale | Standard Deviation 14.475 |
| Part A | Change From Baseline in Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) Total Activity Score | end of follow-up | -9.98 score on a scale | Standard Deviation 18.369 |
| Part B | Change From Baseline in Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) Total Activity Score | end of treatment | -6.591 score on a scale | Standard Deviation 4.7664 |
| Part B | Change From Baseline in Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) Total Activity Score | end of follow-up | -5.705 score on a scale | Standard Deviation 4.6248 |
Secondary
Change From Baseline in Treatment of Autoimmune Bullous Diseases Quality of Life (TABQOL) Scores
TABQOL score ranged from 0 to 68 points representing disease activity (higher scores mean a worse outcome).
Time frame: Part A: until 24 weeks and Part B: until 28 weeks
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Change From Baseline in Treatment of Autoimmune Bullous Diseases Quality of Life (TABQOL) Scores | end of treatment | -0.0 score on a scale | Standard Deviation 6.73 |
| Part A | Change From Baseline in Treatment of Autoimmune Bullous Diseases Quality of Life (TABQOL) Scores | end of follow-up | -0.1 score on a scale | Standard Deviation 5.92 |
| Part B | Change From Baseline in Treatment of Autoimmune Bullous Diseases Quality of Life (TABQOL) Scores | end of treatment | -2.00 score on a scale | Standard Deviation 6.051 |
| Part B | Change From Baseline in Treatment of Autoimmune Bullous Diseases Quality of Life (TABQOL) Scores | end of follow-up | -2.14 score on a scale | Standard Deviation 5.655 |
Secondary
Cumulative Corticosteroid Usage
Cumulative corticosteroid usage
Time frame: Part A: until 24 weeks and Part B: until 28 weeks
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A | Cumulative Corticosteroid Usage | 983.43 mg | Standard Deviation 827.676 |
| Part B | Cumulative Corticosteroid Usage | 2089.600 mg | Standard Deviation 1274.011 |
Secondary
Percentage Change From Baseline in Pemphigus Disease Area Index (PDAI) Total Activity Scores
The PDAI questionnaire has 2 components including activity and damage. The activity component consists of skin, scalp and mucosa parts, and the damage component consists of skin and scalp parts. The total activity score was used for the summary of PDAI scores. PDAI total activity score = Total skin activity + Total scalp activity + Total mucosa activity. PDAI Total Activity Score ranged from 0 to 250 points representing disease activity (higher scores mean a worse outcome). Negative change in total activity score from baseline indicates improvement in pemphigus activity.
Time frame: Part A: until 24 weeks and Part B: until 28 weeks
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Percentage Change From Baseline in Pemphigus Disease Area Index (PDAI) Total Activity Scores | end of treatment | -55.7 score on a scale | Standard Deviation 40.91 |
| Part A | Percentage Change From Baseline in Pemphigus Disease Area Index (PDAI) Total Activity Scores | end of follow-up | -57.7 score on a scale | Standard Deviation 38.45 |
| Part B | Percentage Change From Baseline in Pemphigus Disease Area Index (PDAI) Total Activity Scores | end of treatment | -78.60 score on a scale | Standard Deviation 35.839 |
| Part B | Percentage Change From Baseline in Pemphigus Disease Area Index (PDAI) Total Activity Scores | end of follow-up | -59.68 score on a scale | Standard Deviation 48.403 |
Secondary
Percentage of Participants Able to Achieve a Complete Response (CR) Without Corticosteroids
CR was defined as complete healing of all lesions and the absence of new lesions.
Time frame: Part A: 12 weeks treatment and Part B: 24 weeks treatment
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A | Percentage of Participants Able to Achieve a Complete Response (CR) Without Corticosteroids | 0 percentage of participants |
| Part B | Percentage of Participants Able to Achieve a Complete Response (CR) Without Corticosteroids | 0 percentage of participants |
Secondary
Percentage of Participants Able to Achieve Complete Remission (CR) Without the Need for Doses of Prednisone or Prednisolone of Greater Than 0.5mg/kg
CR was defined as complete healing of all lesions and the absence of new lesions.
Time frame: Part A: 12 weeks treatment and Part B: 24 weeks treatment
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A | Percentage of Participants Able to Achieve Complete Remission (CR) Without the Need for Doses of Prednisone or Prednisolone of Greater Than 0.5mg/kg | 14.8 percentage of participants |
| Part B | Percentage of Participants Able to Achieve Complete Remission (CR) Without the Need for Doses of Prednisone or Prednisolone of Greater Than 0.5mg/kg | 33.3 percentage of participants |
Secondary
Percentage of Participants Able to Achieve Control of Disease Activity (CDA) Without Corticosteroids Within 4 Weeks
CDA was defined as the time at which new lesions cease to form and established lesions begin to heal.
Time frame: 4 weeks
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A | Percentage of Participants Able to Achieve Control of Disease Activity (CDA) Without Corticosteroids Within 4 Weeks | 11.1 percentage of participants |
| Part B | Percentage of Participants Able to Achieve Control of Disease Activity (CDA) Without Corticosteroids Within 4 Weeks | 6.7 percentage of participants |
Secondary
Time to Complete Remission (CR)
CR was defined as complete healing of all lesions and the absence of new lesions.
Time frame: Part A: until 24 weeks and Part B: until 28 weeks
Population: ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A | Time to Complete Remission (CR) | NA days |
| Part B | Time to Complete Remission (CR) | NA days |
Secondary
Time to Control of Disease Activity (CDA)
CDA was defined as the time at which new lesions cease to form and established lesions begin to heal. Kaplan-Meier estimate median time is reported.
Time frame: Part A: until 24 weeks and Part B: until 28 weeks
Population: ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A | Time to Control of Disease Activity (CDA) | 33.0 days |
| Part B | Time to Control of Disease Activity (CDA) | 29.0 days |
Secondary
Time to End of Consolidation Phase (ECP)
ECP was defined as the time at which no new lesions have developed for minimum of 2 weeks, and approximately 80% of existing lesions have healed. The median time to ECP was based on Kaplan-Meier estimate which considered censoring at end of follow-up for patients who didn't have an event. A +/-3 days window for visits at Week 3 and 5, and +/-7 days window for visits at Week 9, 13, 17, 21, 25.
Time frame: Part A: until 24 weeks and Part B: until 28 weeks
Population: ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A | Time to End of Consolidation Phase (ECP) | 170.0 days |
| Part B | Time to End of Consolidation Phase (ECP) | 58.0 days |
Secondary
Time to Relapse After PRN1008 Treatment Discontinuation
Relapse was defined as appearance of ≥3 new lesions/month that do not heal spontaneously within 1 week, or by extension of established lesions, in a patient who has achieved disease control. The median time to relapse was based on Kaplan-Meier estimate which considered censoring at end of follow-up for patients who didn't have an event. A +/-3 days window for visits at Week 3 and 5, and +/-7 days window for visits at Week 9, 13, 17, 21, 25.
Time frame: Part A: until 24 weeks and Part B: until 28 weeks
Population: ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A | Time to Relapse After PRN1008 Treatment Discontinuation | 96.0 days |
| Part B | Time to Relapse After PRN1008 Treatment Discontinuation | 198.0 days |