A Phase 2 interventional study of PRN1008 in Pemphigus Vulgaris, sponsored by Principia Biopharma, a Sanofi Company. Completed at 13 sites in 5 countries. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2023-02-13.
Sponsored by Principia Biopharma, a Sanofi Company (part of Sanofi) · Phase 2, Interventional, and Treatment
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.
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
76 studies on the registry are indexed under Pemphigus; 18 are open to participants now.
This study's enrollment of 42 is above the median of 30 across 53 interventional studies indexed under Pemphigus.
Browse Pemphigus studies →Principia Biopharma, a Sanofi Company is the lead sponsor of 10 studies on the registry; none are open to participants now.
Of its 8 completed or terminated interventional studies of FDA-regulated products, 5 (63%) have results posted.
First submitted before Principia Biopharma became part of Sanofi.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Male or female patients, aged 18 to 80 years old, with -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:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Part A: Open-label PRN1008, 12 weeks; 12 weeks follow-up; Part B: Open-label PRN1008, 24 weeks; 4 weeks follow-up
Drug: PRN1008
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.
Also known as: BTK inhibitor, Rilzabrutinib
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
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
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
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
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
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
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
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
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
Cumulative Corticosteroid Usage
Cumulative corticosteroid usage
Time frame: Part A: until 24 weeks and Part B: until 28 weeks
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
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
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
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
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
The study was conducted at 13 centers in 5 countries from 22 January 2016 to 10 January 2020.
| Milestone | Part A | Part B |
|---|---|---|
| Started | 27 | 0 |
| Completed | 24 | 0 |
| Not completed | 3 | 0 |
| Withdrew: Adverse event | 3 | 0 |
| Milestone | Part A | Part B |
|---|---|---|
| Started | 0 | 15 |
| Completed | 0 | 14 |
| Not completed | 0 | 1 |
| Withdrew: Worsening of pemphigus | 0 | 1 |
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 | Part A | Part B |
|---|---|---|
| Any TEAE | 74.1 | 86.7 |
| Any serious TEAE | 11.1 | 0 |
| Any TEAE leading to treatment discontinuation | 11.1 | 0 |
CDA was defined as the time at which new lesions cease to form and established lesions begin to heal.
| percentage of participants | Part A | 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 | 51.9 (31.9 to 71.3) | 60.0 (32.29 to 83.66) |
CDA was defined as the time at which new lesions cease to form and established lesions begin to heal.
| percentage of participants | Part A | Part B |
|---|---|---|
| Percentage of Participants Able to Achieve Control of Disease Activity (CDA) Without Corticosteroids Within 4 Weeks | 11.1 (2.4 to 29.2) | 6.7 (0.17 to 31.95) |
CR was defined as complete healing of all lesions and the absence of new lesions.
| percentage of participants | Part A | Part B |
|---|---|---|
| Percentage of Participants Able to Achieve a Complete Response (CR) Without Corticosteroids | 0 | 0 |
CR was defined as complete healing of all lesions and the absence of new lesions.
| percentage of participants | Part A | 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 | 14.8 (4.2 to 33.7) | 33.3 (11.82 to 61.62) |
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.
| days | Part A | Part B |
|---|---|---|
| Time to Control of Disease Activity (CDA) | 33.0 (29.0 to 58.0) | 29.0 (15.0 to 34.0) |
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.
| days | Part A | Part B |
|---|---|---|
| Time to End of Consolidation Phase (ECP) | 170.0 (95.0 to NA) | 58.0 (48.0 to NA) |
CR was defined as complete healing of all lesions and the absence of new lesions.
| days | Part A | Part B |
|---|---|---|
| Time to Complete Remission (CR) | NA (NA to NA) | NA (NA to NA) |
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.
| days | Part A | Part B |
|---|---|---|
| Time to Relapse After PRN1008 Treatment Discontinuation | 96.0 (27.0 to 99.0) | 198.0 (41.0 to 209.0) |
Cumulative corticosteroid usage
| mg | Part A | Part B |
|---|---|---|
| Cumulative Corticosteroid Usage | 983.43 ± 827.676 | 2089.600 ± 1274.011 |
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.
| score on a scale | Part A | Part B |
|---|---|---|
| end of treatment | -55.7 ± 40.91 | -78.60 ± 35.839 |
| end of follow-up | -57.7 ± 38.45 | -59.68 ± 48.403 |
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.
| score on a scale | Part A | Part B |
|---|---|---|
| end of treatment | -8.18 ± 14.475 | -6.591 ± 4.7664 |
| end of follow-up | -9.98 ± 18.369 | -5.705 ± 4.6248 |
ABQOL score ranged from 0 to 68 points representing disease activity (higher scores mean a worse outcome).
| score on a scale | Part A | Part B |
|---|---|---|
| end of treatment | -3.7 ± 6.96 | -6.36 ± 9.394 |
| end of follow-up | -2.9 ± 6.71 | -3.79 ± 9.569 |
TABQOL score ranged from 0 to 68 points representing disease activity (higher scores mean a worse outcome).
| score on a scale | Part A | Part B |
|---|---|---|
| end of treatment | -0.0 ± 6.73 | -2.00 ± 6.051 |
| end of follow-up | -0.1 ± 5.92 | -2.14 ± 5.655 |
Simplified Nutritional Appetite Questionnaire (SNAQ) score ranged from 0 to 20 points representing disease activity (higher scores mean a better outcome).
| units on a scale | Part A | Part B |
|---|---|---|
| end of treatment | 1.1 ± 2.45 | 0.21 ± 2.082 |
| end of follow-up | 1.0 ± 2.84 | 0.50 ± 2.103 |
Collected over Part A: until 24 weeks and Part B: until 28 weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part A | 0/27 (0%) | 3/27 (11.1%) | 20/27 (74.1%) |
| Part B | 0/15 (0%) | 0/15 (0%) | 13/15 (86.7%) |
| Event | Part A | Part B |
|---|---|---|
| Pulmonary sequestrationCongenital, familial and genetic disorders | 1/27 | 0/15 |
| Pancreatic pseudocystGastrointestinal disorders | 1/27 | 0/15 |
| CellulitisInfections and infestations | 1/27 | 0/15 |
| PneumonitisRespiratory, thoracic and mediastinal disorders | 1/27 | 0/15 |
| Event | Part A | Part B |
|---|---|---|
| NauseaGastrointestinal disorders | 6/27 | 4/15 |
| HeadacheNervous system disorders | 4/27 | 1/15 |
| DizzinessNervous system disorders | 2/27 | 2/15 |
| Abdominal distensionGastrointestinal disorders | 1/27 | 2/15 |
| Abdominal pain upperGastrointestinal disorders | 3/27 | 1/15 |
| DiarrhoeaGastrointestinal disorders | 3/27 | 0/15 |
| Abdominal painGastrointestinal disorders | 2/27 | 0/15 |
| Dry mouthGastrointestinal disorders | 2/27 | 0/15 |
| VomitingGastrointestinal disorders | 2/27 | 0/15 |
| Staphylococcal skin infectionInfections and infestations | 2/27 | 0/15 |
One patient who completed Part A of the study and later relapsed was enrolled in Part B. Therefore baseline results of one patient are repeated in Part B and total patient number is 15.
| Age, Categorical(Participants) | Part A | Part B | Total |
|---|---|---|---|
| Part A — <=18 years | 0 | 0 | 0 |
| Part A — Between 18 and 65 years | 24 | 0 | 24 |
| Part A — >=65 years | 3 | 0 | 3 |
| Part B — <=18 years | 0 | 0 | 0 |
| Part B — Between 18 and 65 years | 0 | 15 | 15 |
| Part B — >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Part A | Part B | Total |
|---|---|---|---|
| Part A — Female | 15 | 0 | 15 |
| Part A — Male | 12 | 0 | 12 |
| Part B — Female | 0 | 7 | 7 |
| Part B — Male | 0 | 8 | 8 |
| Race (NIH/OMB)(Participants) | Part A | Part B | Total |
|---|---|---|---|
| Part A — American Indian or Alaska Native | 0 | 0 | 0 |
| Part A — Asian | 1 | 0 | 1 |
| Part A — Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Part A — Black or African American | 0 | 0 | 0 |
| Part A — White | 22 | 0 | 22 |
| Part A — More than one race | 0 | 0 | 0 |
| Part A — Unknown or Not Reported | 4 | 0 | 4 |
| Part B — American Indian or Alaska Native | 0 | 0 | 0 |
| Part B — Asian | 0 | 2 | 2 |
| Part B — Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Part B — Black or African American | 0 | 0 | 0 |
| Part B — White | 0 | 8 | 8 |
| Part B — More than one race | 0 | 0 | 0 |
| Part B — Unknown or Not Reported | 0 | 5 | 5 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Ran from Jan 2016 to primary completion in Dec 2019, 46 months.
Results were first posted in Feb 2023, 3 years 1 month after primary completion. A results delay was requested in Dec 2020.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Dec 2022. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Rilzabrutinib
Principia Biopharma, a Sanofi Company →