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Study of Efficacy and Safety of VAY736 in Patients With Pemphigus Vulgaris

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01930175
Recruitment Status : Terminated (The study recruitment was terminated in Dec-2015 for strategic reasons related to the development of the compound.)
First Posted : August 28, 2013
Results First Posted : October 19, 2020
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Pemphigus Vulgaris
Interventions Drug: VAY736
Drug: Placebo
Enrollment 13
Recruitment Details A total of 13 participants were enrolled and randomized into the study from Austria (1 center); Bulgaria (1 center); Taiwan (1 center); USA (2 centers).
Pre-assignment Details The study was planned to be conducted in approximately 32 patients. However, after enrolling 13 patients, the recruitment was terminated due to strategic reasons related to the development of the compound.
Arm/Group Title VAY736 3 mg/kg VAY736 10 mg/kg Placebo
Hide Arm/Group Description single dose iv of VAY736 at a dose of 3mg/kg single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo single dose iv of Placebo
Period Title: Core Study
Started 7 2 4
Safety Analysis Set [1] 7 2 4
Pharmacokinetics (PK) Analysis Set [2] 7 2 0 [3]
Completed 7 1 3
Not Completed 0 1 1
Reason Not Completed
Lost to Follow-up             0             1             0
Adverse Event             0             0             1
[1]
Patients that received study drug
[2]
Patients with at least one PK measurement and no major protocol deviations affecting PK
[3]
Placebo patients were excluded from the PK analyses
Period Title: Open Label VAY736 10 mg/kg at Week 24
Started 0 [1] 0 [1] 3 [1]
Completed 0 0 3
Not Completed 0 0 0
[1]
Only patients originally randomized to Placebo were allowed to enter this Period.
Arm/Group Title VAY736 3 mg/kg VAY736 10 mg/kg Placebo Total
Hide Arm/Group Description single dose iv of VAY736 at a dose of 3mg/kg single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo single dose iv of Placebo Total of all reporting groups
Overall Number of Baseline Participants 7 2 4 13
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants 2 participants 4 participants 13 participants
51.6  (10.45) 35.0  (8.49) 56.0  (8.83) 50.4  (11.44)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 2 participants 4 participants 13 participants
Female
3
  42.9%
0
   0.0%
2
  50.0%
5
  38.5%
Male
4
  57.1%
2
 100.0%
2
  50.0%
8
  61.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 7 participants 2 participants 4 participants 13 participants
Asian
2
  28.6%
1
  50.0%
1
  25.0%
4
  30.8%
Caucasian
4
  57.1%
1
  50.0%
3
  75.0%
8
  61.5%
Other
1
  14.3%
0
   0.0%
0
   0.0%
1
   7.7%
1.Primary Outcome
Title Pemphigus Disease Area Index (PDAI) at Week 12
Hide Description PDAI is specific cutaneous and mucosal disease activity assessment performed by investigator based on evaluation of lesions in well-defined anatomical locations. The score weighted for the number and size of lesions with score of 0 (absent) to 10 given for skin (12 body locations), scalp and mucous membrane showing disease activity (erosions/blisters or new erythema). Damage, such as post inflammatory hyperpigmentation or erythema from resolving lesion, scored separately from the main score as absent (0) or present (1) for each body area or scalp resulting in a score of 0 to 12 or 0 to 1, respectively. Thus, PDAI ranged from 0 to 263, with 250 points representing disease activity (120 points for skin activity; 10 points for scalp activity; 120 points for mucosal activity) and 13 points representing disease damage.
Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All evaluable patients.
Arm/Group Title VAY736 3 mg/kg VAY736 10 mg/kg Placebo
Hide Arm/Group Description:
single dose iv of VAY736 at a dose of 3mg/kg
single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo
single dose iv of Placebo
Overall Number of Participants Analyzed 7 2 3
Mean (Standard Deviation)
Unit of Measure: Score on the scale
5.90  (1.836) 10.15  (8.273) 22.07  (25.628)
2.Secondary Outcome
Title Autoimmune Skin Disease Intensity Score (ABSIS) at Baseline and Week 12.
Hide Description The ABSIS Score is a quality- and quantity-based score for cutaneous and oral mucosal lesions combining the extent of the affected body surface area (BSA), the quality of the skin lesions and oral involvement. The ABSIS score ranged from 0 to 206 with 150 points for skin involvement, 11 points for oral involvement and 45 points for subjective discomfort during eating and drinking. A reduction from baseline (or, a negative change from baseline) in ABSIS indicates improvement in patients.
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All evaluable patients.
Arm/Group Title VAY736 3 mg/kg VAY736 10 mg/kg Placebo
Hide Arm/Group Description:
single dose iv of VAY736 at a dose of 3mg/kg
single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo
single dose iv of Placebo
Overall Number of Participants Analyzed 7 2 4
Mean (Standard Deviation)
Unit of Measure: Score on the scale
Baseline Number Analyzed 7 participants 2 participants 4 participants
13.26  (7.621) 16.38  (12.905) 33.75  (21.620)
Week 12 Number Analyzed 7 participants 2 participants 3 participants
2.19  (3.465) 5.55  (7.707) 16.17  (25.838)
3.Secondary Outcome
Title Change From Baseline in Investigator Global Assessment (IGA) at Week 12
Hide Description

The IGA score ranges from 0 to 4 and the decrease or reduction from baseline in IGA score indicates improvement in patients.

IGA score scale:

0=Clear, 1=Near Clear, 2=Mild, 3=Moderate, 4=Severe active disease
Time Frame Baseline, Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All evaluable patients.
Arm/Group Title VAY736 3 mg/kg VAY736 10 mg/kg Placebo
Hide Arm/Group Description:
single dose iv of VAY736 at a dose of 3mg/kg
single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo
single dose iv of Placebo
Overall Number of Participants Analyzed 7 2 3
Mean (Standard Deviation)
Unit of Measure: Score on the scale
-1.4  (0.79) -1.0  (0.00) -0.7  (0.58)
4.Secondary Outcome
Title VAY736 Serum Concentration - AUCinf
Hide Description The area under the serum concentration-time curve from time zero to infinity [mass × time / volume]. The concentration of VAY736 was measured in the serum.
Time Frame predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set: Patients with at least one PK measurement and no major protocol deviations affecting PK
Arm/Group Title VAY736 3 mg/kg VAY736 10 mg/kg Placebo
Hide Arm/Group Description:
single dose iv of VAY736 at a dose of 3mg/kg
single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo
single dose iv of Placebo
Overall Number of Participants Analyzed 7 2 0
Mean (Standard Deviation)
Unit of Measure: day*ug/mL
440  (114) 1480  (231)
5.Secondary Outcome
Title VAY736 Serum Concentration - AUClast
Hide Description The area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration [mass × time / volume]. The concentration of VAY736 was measured in the serum.
Time Frame predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set: Patients with at least one PK measurement and no major protocol deviations affecting PK
Arm/Group Title VAY736 3 mg/kg VAY736 10 mg/kg Placebo
Hide Arm/Group Description:
single dose iv of VAY736 at a dose of 3mg/kg
single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo
single dose iv of Placebo
Overall Number of Participants Analyzed 7 2 0
Mean (Standard Deviation)
Unit of Measure: day*ug/mL
440  (114) 1480  (231)
6.Secondary Outcome
Title VAY736 Serum Concentration - Cmax
Hide Description The observed maximum serum concentration following drug administration [mass / volume]. The concentration of VAY736 was measured in the serum.
Time Frame predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set: Patients with at least one PK measurement and no major protocol deviations affecting PK
Arm/Group Title VAY736 3 mg/kg VAY736 10 mg/kg Placebo
Hide Arm/Group Description:
single dose iv of VAY736 at a dose of 3mg/kg
single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo
single dose iv of Placebo
Overall Number of Participants Analyzed 7 2 0
Mean (Standard Deviation)
Unit of Measure: ug/mL
77.1  (13.0) 230  (2.83)
7.Secondary Outcome
Title VAY736 Serum Concentration - Tmax
Hide Description Tmax is the time to reach the maximum concentration after drug administration [time]. The concentration of VAY736 was measured in the serum.
Time Frame predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set: Patients with at least one PK measurement and no major protocol deviations affecting PK
Arm/Group Title VAY736 3 mg/kg VAY736 10 mg/kg Placebo
Hide Arm/Group Description:
single dose iv of VAY736 at a dose of 3mg/kg
single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo
single dose iv of Placebo
Overall Number of Participants Analyzed 7 2 0
Median (Full Range)
Unit of Measure: Hours
2.05
(2.00 to 2.22)
2.11
(2.00 to 2.22)
8.Secondary Outcome
Title VAY736 Serum Concentration - T1/2
Hide Description T1/2 is the terminal elimination half-life [time]. The concentration of VAY736 was measured in the serum.
Time Frame predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set: Patients with at least one PK measurement and no major protocol deviations affecting PK
Arm/Group Title VAY736 3 mg/kg VAY736 10 mg/kg Placebo
Hide Arm/Group Description:
single dose iv of VAY736 at a dose of 3mg/kg
single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo
single dose iv of Placebo
Overall Number of Participants Analyzed 7 2 0
Mean (Standard Deviation)
Unit of Measure: Days
11.2  (2.01) 15.4  (1.93)
Time Frame Adverse events were collected from first dose of study treatment until end of study for up to 5 years.
Adverse Event Reporting Description Any sign or symptom until end of study for up to 5 years.
 
Arm/Group Title VAY736 3 mg/kg VAY736 10 mg/kg Placebo Open Label VAY736 10 mg/kg
Hide Arm/Group Description single dose iv of VAY736 at a dose of 3mg/kg single dose iv of VAY736 at a dose of 10mg/kg initiated following a safety review of patients receiving VAY736 3 mg/kg or placebo single dose iv of Placebo Patients randomized to placebo in period 1 received open label VAY736 10mg/kg at week 24.
All-Cause Mortality
VAY736 3 mg/kg VAY736 10 mg/kg Placebo Open Label VAY736 10 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/7 (0.00%)   0/2 (0.00%)   0/4 (0.00%)   0/3 (0.00%) 
Hide Serious Adverse Events
VAY736 3 mg/kg VAY736 10 mg/kg Placebo Open Label VAY736 10 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/7 (14.29%)   0/2 (0.00%)   1/4 (25.00%)   1/3 (33.33%) 
Eye disorders         
Cataract † 1  0/7 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Gastrointestinal disorders         
Duodenal ulcer † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Skin and subcutaneous tissue disorders         
Pemphigus † 1  0/7 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
1
Term from vocabulary, MedDRA (19.1)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
VAY736 3 mg/kg VAY736 10 mg/kg Placebo Open Label VAY736 10 mg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/7 (85.71%)   2/2 (100.00%)   3/4 (75.00%)   3/3 (100.00%) 
Cardiac disorders         
Arrhythmia † 1  0/7 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Eye disorders         
Conjunctivitis allergic † 1  0/7 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Gastrointestinal disorders         
Diarrhoea † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Flatulence † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Gingival recession † 1  0/7 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Nausea † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Oral pain † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Toothache † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
General disorders         
Chills † 1  0/7 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Fatigue † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Influenza like illness † 1  0/7 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Pain † 1  0/7 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Pyrexia † 1  0/7 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Infections and infestations         
Bronchitis † 1  0/7 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Dermatophytosis of nail † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Herpes simplex † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Impetigo † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Laryngitis † 1  0/7 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Nasopharyngitis † 1  1/7 (14.29%)  0/2 (0.00%)  1/4 (25.00%)  1/3 (33.33%) 
Oral fungal infection † 1  0/7 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Otitis media † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Paronychia † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Rhinitis † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Tooth abscess † 1  0/7 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Upper respiratory tract infection † 1  1/7 (14.29%)  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Injury, poisoning and procedural complications         
Infusion related reaction † 1  0/7 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Investigations         
Amylase increased † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Blood bilirubin increased † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Blood calcium decreased † 1  0/7 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Blood magnesium decreased † 1  0/7 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Blood potassium increased † 1  0/7 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Lipase increased † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Back pain † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Osteoarthritis † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Pain in extremity † 1  0/7 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Skin papilloma † 1  0/7 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Nervous system disorders         
Dizziness † 1  1/7 (14.29%)  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Headache † 1  2/7 (28.57%)  1/2 (50.00%)  0/4 (0.00%)  1/3 (33.33%) 
Sciatica † 1  0/7 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Psychiatric disorders         
Insomnia † 1  2/7 (28.57%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough † 1  3/7 (42.86%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Dysphonia † 1  0/7 (0.00%)  0/2 (0.00%)  1/4 (25.00%)  0/3 (0.00%) 
Dyspnoea † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Oropharyngeal pain † 1  2/7 (28.57%)  1/2 (50.00%)  0/4 (0.00%)  1/3 (33.33%) 
Rhinorrhoea † 1  0/7 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
Skin and subcutaneous tissue disorders         
Alopecia † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Dermatitis † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Mechanical urticaria † 1  0/7 (0.00%)  0/2 (0.00%)  0/4 (0.00%)  1/3 (33.33%) 
Rash † 1  1/7 (14.29%)  0/2 (0.00%)  0/4 (0.00%)  0/3 (0.00%) 
Vascular disorders         
Orthostatic hypotension † 1  0/7 (0.00%)  1/2 (50.00%)  0/4 (0.00%)  0/3 (0.00%) 
1
Term from vocabulary, MedDRA (19.1)
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: Novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01930175    
Other Study ID Numbers: CVAY736X2203
First Submitted: August 23, 2013
First Posted: August 28, 2013
Results First Submitted: September 24, 2020
Results First Posted: October 19, 2020
Last Update Posted: October 19, 2020