Trial Outcomes & Findings for Study of Efficacy and Safety of VAY736 in Patients With Pemphigus Vulgaris (NCT NCT01930175)

NCT ID: NCT01930175

Last Updated: 2021-10-08

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 13 participants
• Primary outcome timeframe: Week 12
• Results posted on: 2021-10-08

Participant Flow

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).

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.

Participant milestones

Measure	VAY736 3 mg/kg single dose iv of VAY736 at a dose of 3mg/kg	VAY736 10 mg/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	Placebo single dose iv of Placebo
Core Study STARTED	7	2	4
Core Study Safety Analysis Set	7	2	4
Core Study Pharmacokinetics (PK) Analysis Set	7	2	0
Core Study COMPLETED	7	1	3
Core Study NOT COMPLETED	0	1	1
Open Label VAY736 10 mg/kg at Week 24 STARTED	0	0	3
Open Label VAY736 10 mg/kg at Week 24 COMPLETED	0	0	3
Open Label VAY736 10 mg/kg at Week 24 NOT COMPLETED	0	0	0

Reasons for withdrawal

Measure	VAY736 3 mg/kg single dose iv of VAY736 at a dose of 3mg/kg	VAY736 10 mg/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	Placebo single dose iv of Placebo
Core Study Lost to Follow-up	0	1	0
Core Study Adverse Event	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	VAY736 3 mg/kg n=7 Participants single dose iv of VAY736 at a dose of 3mg/kg	VAY736 10 mg/kg n=2 Participants 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	Placebo n=4 Participants single dose iv of Placebo	Total n=13 Participants Total of all reporting groups
Age, Continuous	51.6 Years STANDARD_DEVIATION 10.45 • n=5 Participants	35.0 Years STANDARD_DEVIATION 8.49 • n=7 Participants	56.0 Years STANDARD_DEVIATION 8.83 • n=5 Participants	50.4 Years STANDARD_DEVIATION 11.44 • n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	4 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 12

Population: All evaluable patients.

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.

Outcome measures

Measure	VAY736 3 mg/kg n=7 Participants single dose iv of VAY736 at a dose of 3mg/kg	VAY736 10 mg/kg n=2 Participants 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	Placebo n=3 Participants single dose iv of Placebo
Pemphigus Disease Area Index (PDAI) at Week 12	5.90 Score on the scale Standard Deviation 1.836	10.15 Score on the scale Standard Deviation 8.273	22.07 Score on the scale Standard Deviation 25.628

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All evaluable patients.

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.

Outcome measures

Measure	VAY736 3 mg/kg n=7 Participants single dose iv of VAY736 at a dose of 3mg/kg	VAY736 10 mg/kg n=2 Participants 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	Placebo n=4 Participants single dose iv of Placebo
Autoimmune Skin Disease Intensity Score (ABSIS) at Baseline and Week 12. Baseline	13.26 Score on the scale Standard Deviation 7.621	16.38 Score on the scale Standard Deviation 12.905	33.75 Score on the scale Standard Deviation 21.620
Autoimmune Skin Disease Intensity Score (ABSIS) at Baseline and Week 12. Week 12	2.19 Score on the scale Standard Deviation 3.465	5.55 Score on the scale Standard Deviation 7.707	16.17 Score on the scale Standard Deviation 25.838

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All evaluable patients.

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

Outcome measures

Measure	VAY736 3 mg/kg n=7 Participants single dose iv of VAY736 at a dose of 3mg/kg	VAY736 10 mg/kg n=2 Participants 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	Placebo n=3 Participants single dose iv of Placebo
Change From Baseline in Investigator Global Assessment (IGA) at Week 12	-1.4 Score on the scale Standard Deviation 0.79	-1.0 Score on the scale Standard Deviation 0.00	-0.7 Score on the scale Standard Deviation 0.58

SECONDARY outcome

Timeframe: predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks

Population: PK analysis set: Patients with at least one PK measurement and no major protocol deviations affecting PK

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.

Outcome measures

Measure	VAY736 3 mg/kg n=7 Participants single dose iv of VAY736 at a dose of 3mg/kg	VAY736 10 mg/kg n=2 Participants 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	Placebo single dose iv of Placebo
VAY736 Serum Concentration - AUCinf	440 day*ug/mL Standard Deviation 114	1480 day*ug/mL Standard Deviation 231	—

SECONDARY outcome

Timeframe: predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks

Population: PK analysis set: Patients with at least one PK measurement and no major protocol deviations affecting PK

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.

Outcome measures

Measure	VAY736 3 mg/kg n=7 Participants single dose iv of VAY736 at a dose of 3mg/kg	VAY736 10 mg/kg n=2 Participants 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	Placebo single dose iv of Placebo
VAY736 Serum Concentration - AUClast	440 day*ug/mL Standard Deviation 114	1480 day*ug/mL Standard Deviation 231	—

SECONDARY outcome

Timeframe: predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks

Population: PK analysis set: Patients with at least one PK measurement and no major protocol deviations affecting PK

The observed maximum serum concentration following drug administration [mass / volume]. The concentration of VAY736 was measured in the serum.

Outcome measures

Measure	VAY736 3 mg/kg n=7 Participants single dose iv of VAY736 at a dose of 3mg/kg	VAY736 10 mg/kg n=2 Participants 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	Placebo single dose iv of Placebo
VAY736 Serum Concentration - Cmax	77.1 ug/mL Standard Deviation 13.0	230 ug/mL Standard Deviation 2.83	—

SECONDARY outcome

Timeframe: predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks

Population: PK analysis set: Patients with at least one PK measurement and no major protocol deviations affecting PK

Tmax is the time to reach the maximum concentration after drug administration [time]. The concentration of VAY736 was measured in the serum.

Outcome measures

Measure	VAY736 3 mg/kg n=7 Participants single dose iv of VAY736 at a dose of 3mg/kg	VAY736 10 mg/kg n=2 Participants 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	Placebo single dose iv of Placebo
VAY736 Serum Concentration - Tmax	2.05 Hours Interval 2.0 to 2.22	2.11 Hours Interval 2.0 to 2.22	—

SECONDARY outcome

Timeframe: predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks

Population: PK analysis set: Patients with at least one PK measurement and no major protocol deviations affecting PK

T1/2 is the terminal elimination half-life [time]. The concentration of VAY736 was measured in the serum.

Outcome measures

Measure	VAY736 3 mg/kg n=7 Participants single dose iv of VAY736 at a dose of 3mg/kg	VAY736 10 mg/kg n=2 Participants 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	Placebo single dose iv of Placebo
VAY736 Serum Concentration - T1/2	11.2 Days Standard Deviation 2.01	15.4 Days Standard Deviation 1.93	—

Adverse Events

VAY736 3 mg/kg

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

VAY736 10 mg/kg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Open Label VAY736 10 mg/kg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	VAY736 3 mg/kg n=7 participants at risk single dose iv of VAY736 at a dose of 3mg/kg	VAY736 10 mg/kg n=2 participants at risk 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	Placebo n=4 participants at risk single dose iv of Placebo	Open Label VAY736 10 mg/kg n=3 participants at risk Patients randomized to placebo in period 1 received open label VAY736 10mg/kg at week 24.
Eye disorders Cataract	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	33.3% 1/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Gastrointestinal disorders Duodenal ulcer	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Skin and subcutaneous tissue disorders Pemphigus	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	25.0% 1/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.

Other adverse events

Measure	VAY736 3 mg/kg n=7 participants at risk single dose iv of VAY736 at a dose of 3mg/kg	VAY736 10 mg/kg n=2 participants at risk 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	Placebo n=4 participants at risk single dose iv of Placebo	Open Label VAY736 10 mg/kg n=3 participants at risk Patients randomized to placebo in period 1 received open label VAY736 10mg/kg at week 24.
Musculoskeletal and connective tissue disorders Osteoarthritis	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Cardiac disorders Arrhythmia	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	25.0% 1/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Eye disorders Conjunctivitis allergic	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	33.3% 1/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Gastrointestinal disorders Diarrhoea	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Gastrointestinal disorders Flatulence	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Gastrointestinal disorders Gingival recession	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	25.0% 1/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Gastrointestinal disorders Nausea	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Gastrointestinal disorders Oral pain	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Gastrointestinal disorders Toothache	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
General disorders Chills	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	50.0% 1/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
General disorders Fatigue	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
General disorders Influenza like illness	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	33.3% 1/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
General disorders Pain	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	50.0% 1/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
General disorders Pyrexia	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	50.0% 1/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Infections and infestations Bronchitis	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	33.3% 1/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Infections and infestations Dermatophytosis of nail	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Infections and infestations Herpes simplex	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	33.3% 1/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Infections and infestations Impetigo	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Infections and infestations Laryngitis	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	25.0% 1/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Infections and infestations Nasopharyngitis	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	25.0% 1/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	33.3% 1/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Infections and infestations Oral fungal infection	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	25.0% 1/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Infections and infestations Otitis media	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Infections and infestations Paronychia	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Infections and infestations Rhinitis	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Infections and infestations Tooth abscess	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	50.0% 1/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Infections and infestations Upper respiratory tract infection	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	50.0% 1/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	50.0% 1/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Investigations Amylase increased	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Investigations Blood bilirubin increased	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Investigations Blood calcium decreased	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	33.3% 1/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Investigations Blood magnesium decreased	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	33.3% 1/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Investigations Blood potassium increased	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	33.3% 1/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Investigations Lipase increased	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Musculoskeletal and connective tissue disorders Arthralgia	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Musculoskeletal and connective tissue disorders Back pain	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	33.3% 1/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	33.3% 1/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Nervous system disorders Dizziness	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	50.0% 1/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Nervous system disorders Headache	28.6% 2/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	50.0% 1/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	33.3% 1/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Nervous system disorders Sciatica	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	50.0% 1/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Psychiatric disorders Insomnia	28.6% 2/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Respiratory, thoracic and mediastinal disorders Cough	42.9% 3/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	25.0% 1/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Respiratory, thoracic and mediastinal disorders Dyspnoea	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	28.6% 2/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	50.0% 1/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	33.3% 1/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	50.0% 1/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Skin and subcutaneous tissue disorders Alopecia	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Skin and subcutaneous tissue disorders Dermatitis	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Skin and subcutaneous tissue disorders Mechanical urticaria	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	33.3% 1/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Skin and subcutaneous tissue disorders Rash	14.3% 1/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.
Vascular disorders Orthostatic hypotension	0.00% 0/7 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	50.0% 1/2 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/4 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.	0.00% 0/3 • Adverse events were collected from first dose of study treatment until end of study for up to 5 years. Any sign or symptom until end of study for up to 5 years.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: Novartis.email@novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER