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NCT02704429

A Study of PRN1008 in Adult Patients With Pemphigus Vulgaris

Completed Phase 2 Results posted Last updated 13 February 2023
What this trial tests

Phase 2 trial testing PRN1008 in Pemphigus Vulgaris in 42 participants. Completed in 10 January 2020.

Timeline
22 January 2016
Primary endpoint
18 December 2019
10 January 2020

Quick facts

Lead sponsorPrincipia Biopharma, a Sanofi Company
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment42
Start date22 January 2016
Primary completion18 December 2019
Estimated completion10 January 2020
Sites13 locations across France, Greece, Israel, Australia, Croatia

Drugs / interventions tested

Conditions studied

Sponsor

Principia Biopharma, a Sanofi Company — full company profile →

Who can join

Adults 18 to 80, any sex, with Pemphigus Vulgaris. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Treatment-emergent Adverse Events Primary · 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.

Any TEAE
GroupValue95% CI
Part A74.1
Part B86.7
Any serious TEAE
GroupValue95% CI
Part A11.1
Part B0
Any TEAE leading to treatment discontinuation
GroupValue95% CI
Part A11.1
Part B0
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 Primary · 4 weeks

CDA was defined as the time at which new lesions cease to form and established lesions begin to heal.

GroupValue95% CI
Part A51.931.9 – 71.3
Part B60.032.29 – 83.66
Percentage of Participants Able to Achieve Control of Disease Activity (CDA) Without Corticosteroids Within 4 Weeks Secondary · 4 weeks

CDA was defined as the time at which new lesions cease to form and established lesions begin to heal.

GroupValue95% CI
Part A11.12.4 – 29.2
Part B6.70.17 – 31.95
Percentage of Participants Able to Achieve a Complete Response (CR) Without Corticosteroids Secondary · 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.

GroupValue95% CI
Part A0
Part B0
Percentage of Participants Able to Achieve Complete Remission (CR) Without the Need for Doses of Prednisone or Prednisolone of Greater Than 0.5mg/kg Secondary · 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.

GroupValue95% CI
Part A14.84.2 – 33.7
Part B33.311.82 – 61.62
Time to Control of Disease Activity (CDA) Secondary · 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.

GroupValue95% CI
Part A33.029.0 – 58.0
Part B29.015.0 – 34.0
Time to End of Consolidation Phase (ECP) Secondary · 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.

GroupValue95% CI
Part A170.095.0 – NA
Part B58.048.0 – NA
Time to Complete Remission (CR) Secondary · 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.

GroupValue95% CI
Part ANANA – NA
Part BNANA – NA
Time to Relapse After PRN1008 Treatment Discontinuation Secondary · 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.

GroupValue95% CI
Part A96.027.0 – 99.0
Part B198.041.0 – 209.0
Cumulative Corticosteroid Usage Secondary · Part A: until 24 weeks and Part B: until 28 weeks

Cumulative corticosteroid usage

GroupValue95% CI
Part A983.43± 827.676
Part B2089.600± 1274.011
Percentage Change From Baseline in Pemphigus Disease Area Index (PDAI) Total Activity Scores Secondary · 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.

end of treatment
GroupValue95% CI
Part A-55.7± 40.91
Part B-78.60± 35.839
end of follow-up
GroupValue95% CI
Part A-57.7± 38.45
Part B-59.68± 48.403
Change From Baseline in Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) Total Activity Score Secondary · 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.

end of treatment
GroupValue95% CI
Part A-8.18± 14.475
Part B-6.591± 4.7664
end of follow-up
GroupValue95% CI
Part A-9.98± 18.369
Part B-5.705± 4.6248

Adverse events — posted to ClinicalTrials.gov

Time frame: Part A: until 24 weeks and Part B: until 28 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part A
Serious: 3/27 (11%)
Deaths: 0/27
Part B
Serious: 0/15 (0%)
Deaths: 0/15

Serious adverse events (4 terms)

ReactionSystemPart APart B
Pulmonary sequestrationCongenital, familial and genetic disorders
Pancreatic pseudocystGastrointestinal disorders
CellulitisInfections and infestations
PneumonitisRespiratory, thoracic and mediastinal disorders
Other adverse events (66 terms — click to expand)

ReactionSystemPart APart B
NauseaGastrointestinal disorders
HeadacheNervous system disorders
Abdominal pain upperGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Abdominal painGastrointestinal disorders
Dry mouthGastrointestinal disorders
VomitingGastrointestinal disorders
Staphylococcal skin infectionInfections and infestations
Upper respiratory tract infectionInfections and infestations
DizzinessNervous system disorders
ParaesthesiaNervous system disorders
FatigueGeneral disorders
Peripheral swellingGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
VertigoEar and labyrinth disorders
AnxietyPsychiatric disorders
ErythemaSkin and subcutaneous tissue disorders
Abdominal distensionGastrointestinal disorders
Change of bowel habitGastrointestinal disorders
Gastrointestinal disorderGastrointestinal disorders
StomatitisGastrointestinal disorders
Teeth brittleGastrointestinal disorders
DermatophytosisInfections and infestations
NasopharyngitisInfections and infestations
Pharyngitis streptococcalInfections and infestations
SinusitisInfections and infestations
TracheitisInfections and infestations
Vaginal infectionInfections and infestations
AlopeciaSkin and subcutaneous tissue disorders
Androgenetic alopeciaSkin and subcutaneous tissue disorders
Erythema nodosumSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
Rash erythematousSkin and subcutaneous tissue disorders
UrticariaSkin and subcutaneous tissue disorders
Back painMusculoskeletal and connective tissue disorders
Musculoskeletal chest painMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Pulmonary sequestration, Pancreatic pseudocyst, Cellulitis, Pneumonitis.

Data from ClinicalTrials.gov NCT02704429 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Pemphigus.
    Kasperkiewicz M, Ellebrecht CT, Takahashi H, Yamagami J, et al · · 2017 · cited 365× · PMID 28492232 · DOI 10.1038/nrdp.2017.26
  2. Kinase inhibition in autoimmunity and inflammation.
    Zarrin AA, Bao K, Lupardus P, Vucic D. · · 2021 · cited 302× · PMID 33077936 · DOI 10.1038/s41573-020-0082-8
  3. Small Molecule NF-κB Pathway Inhibitors in Clinic.
    Ramadass V, Vaiyapuri T, Tergaonkar V. · · 2020 · cited 154× · PMID 32708302 · DOI 10.3390/ijms21145164
  4. Pemphigus: Current and Future Therapeutic Strategies.
    Didona D, Maglie R, Eming R, Hertl M. · · 2019 · cited 149× · PMID 31293582 · DOI 10.3389/fimmu.2019.01418
  5. Tyrosine Kinases in Autoimmune and Inflammatory Skin Diseases.
    Szilveszter KP, Németh T, Mócsai A. · · 2019 · cited 102× · PMID 31447854 · DOI 10.3389/fimmu.2019.01862
  6. Bruton's Tyrosine Kinase (BTK) Inhibitors and Autoimmune Diseases: Making Sense of BTK Inhibitor Specificity Profiles and Recent Clinical Trial Successes and Failures.
    Ringheim GE, Wampole M, Oberoi K. · · 2021 · cited 100× · PMID 34803999 · DOI 10.3389/fimmu.2021.662223
  7. B Cell Modulation Strategies in Autoimmune Diseases: New Concepts.
    Musette P, Bouaziz JD. · · 2018 · cited 86× · PMID 29706952 · DOI 10.3389/fimmu.2018.00622
  8. Bruton's tyrosine kinase inhibition-An emerging therapeutic strategy in immune-mediated dermatological conditions.
    Mendes-Bastos P, Brasileiro A, Kolkhir P, Frischbutter S, et al · · 2022 · cited 67× · PMID 35175630 · DOI 10.1111/all.15261

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