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

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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 )

Tracking Information
First Submitted Date  ICMJE August 23, 2013
First Posted Date  ICMJE August 28, 2013
Results First Submitted Date  ICMJE September 24, 2020
Results First Posted Date  ICMJE October 19, 2020
Last Update Posted Date October 19, 2020
Actual Study Start Date  ICMJE December 18, 2013
Actual Primary Completion Date September 25, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 24, 2020)
Pemphigus Disease Area Index (PDAI) at Week 12 [ Time Frame: Week 12 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 23, 2013)
Efficacy of a single intravenous dose of VAY736 in reducing the clinical disease activity in pemphigus vulgaris patinets. [ Time Frame: baseline, 12 weeks ]
The effect of VAY736 on clinical disease activity will be measured by the change in Pemphigus Disease Area Index (PDAI) between baseline and week 12. PDAI is an assessment of skin and mucosal disease activity by the Investigator. The score incorporates the number and size of lesions across multiple skin locations and the mucous membranes.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2020)
  • Autoimmune Skin Disease Intensity Score (ABSIS) at Baseline and Week 12. [ Time Frame: Baseline, Week 12 ]
    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.
  • Change From Baseline in Investigator Global Assessment (IGA) at Week 12 [ Time Frame: Baseline, Week 12 ]
    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
  • VAY736 Serum Concentration - AUCinf [ Time Frame: predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks ]
    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.
  • VAY736 Serum Concentration - AUClast [ Time Frame: predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks ]
    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.
  • VAY736 Serum Concentration - Cmax [ Time Frame: predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks ]
    The observed maximum serum concentration following drug administration [mass / volume]. The concentration of VAY736 was measured in the serum.
  • VAY736 Serum Concentration - Tmax [ Time Frame: predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks ]
    Tmax is the time to reach the maximum concentration after drug administration [time]. The concentration of VAY736 was measured in the serum.
  • VAY736 Serum Concentration - T1/2 [ Time Frame: predose, 2, 24 hours and weeks 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks ]
    T1/2 is the terminal elimination half-life [time]. The concentration of VAY736 was measured in the serum.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 23, 2013)
  • Number of patients with adverse events [ Time Frame: up to an average of 12 months ]
    Summarized statistics on adverse events will be reported under categories such as total adverse events, serious adverse events and death
  • Change in Autoimmune Skin disease Intensity Score (ABSIS) [ Time Frame: 12 weeks ]
    The effect of VAY736 on the ABSIS score will be compared betwen baseline and Week 12. ABSIS is a quality and quantity-based score of skin and oral mucosal lesions, combining the extent of the affected body surface area, the quality of the lesion and the extent of oral mucosal involvement, including food-related pain and discomfort.
  • Change in Investigator Global Assessment (IGA) [ Time Frame: baseline, 12 weeks ]
    The effect of VAY736 on the IGA of a patient's disease activity will compared between baseline and Week 12. The IGA score ranges from 0 (no sign of active disease) to 4 (Severe active disease)
  • VAY736 serum concentration [ Time Frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks ]
    The concentration of VAY736 will be measured in the serum. Descriptive statistics will include area under the concentration curve, half-life and time to maximum concentration.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Efficacy and Safety of VAY736 in Patients With Pemphigus Vulgaris
Official Title  ICMJE A Randomized, Partial-blind, Placebo-controlled Trial Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of VAY736 in the Treatment of Patients With Pemphigus Vulgaris
Brief Summary The study evaluated the efficacy, safety and pharmacokinetics of VAY736 in the treatment of patients with pemphigus vulagaris (PV).
Detailed Description

This was a non-confirmatory, randomized, partial-blind, placebo-controlled trial evaluating the efficacy, safety and pharmacokinetics (PK) of VAY736 in the treatment of PV patients.

A total of 13 patients were enrolled and randomized into the study. Of these 13 patients,seven were randomized to the 3 mg/kg VAY736 group, two were randomized to the 10 mg/kg VAY736 group and four were randomized to the placebo group.In the placebo group, three out of the four patients consented to open-label VAY736 treatment and received 10 mg/kg VAY736 after Week 24 onwards. Thus, a total of 12 patients received VAY736, 7 patients received 3 mg/kg and 5 patients 10 mg/kg.

The Screening period consisted of a Screening Visit performed within 28 days prior to randomization to assess patient eligibility. Following Screening, patients underwent pre-dose procedures which included assessment of their PV by Pemphigus Disease Area Index (PDAI), Autoimmune Bullous Skin disease Intensity Score (ABSIS) and Investigator Global Assessment (IGA), and blood sampling for PK endpoints. Patients then received the study drug, which was administered over approximately a 2 hour period. The patients remained in the study center overnight post-infusion for observation and for measurement of safety parameters and PK samples approximately 24 h post-infusion (start of infusion: ±2 h). Patients were then discharged from the study site and returned as per the schedule. Patients were evaluated at Week 1, Week 2 and Week 3, then every 3 weeks through to Week 12, and every 4 weeks through to Week 24. At Week 24, the blind was broken to confirm treatment allocation. If a patient was on placebo, such patient completing the Week 24 visit and after unblinding had the option of receiving open label VAY736 10mg/kg.

Recruitment was paused in Mar-2015 and at the time 13 patients were enrolled. The study recruitment was then terminated in Dec-2015 for strategic reasons related to the development of the compound.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Pemphigus Vulgaris
Intervention  ICMJE
  • Drug: VAY736
    Other Name: Ianalumab
  • Drug: Placebo
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    single dose iv of Placebo
    Intervention: Drug: Placebo
  • Experimental: VAY736 3 mg/kg
    single dose iv of VAY736 at a dose of 3mg/kg
    Intervention: Drug: VAY736
  • Experimental: 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.
    Intervention: Drug: VAY736
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 24, 2020)
13
Original Estimated Enrollment  ICMJE
 (submitted: August 23, 2013)
30
Actual Study Completion Date  ICMJE September 25, 2019
Actual Primary Completion Date September 25, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adult patients 20 to 70 years of age
  • Confirmed diagnosis of pemphigus vulgaris
  • Presence of mild to moderate pemphigus vulgaris
  • Patients must weight between 40 kg and 150 kg inclusive
  • on a stable dose of oral corticosteriod therapy (with or without azathioprine or mycophenolate)

Exclusion Criteria:

  • Pregnant or nursing (lactating) women
  • Women of child-bearing potential unless they are using a highly effective method of birth control during dosing and for 4 months following study treatment
  • Recent previous treatment with photo therapy, biological therapy, steroids, immunosuppresive agents (unless washout period applied)
  • Active or recent history of clinically significant infection
  • use of rituximab within 1 year Other protocol-defined inclusion/exclusion criteria may apply.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Bulgaria,   Taiwan,   United States
Removed Location Countries Germany,   Israel,   Italy,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT01930175
Other Study ID Numbers  ICMJE CVAY736X2203
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP