Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis (AB06006)

November 29, 2019 updated by: AB Science

Randomized, Placebo-controlled, Phase 3 Study to Compare Efficacy and Safety of Masitinib at 6 mg/kg/Day to Placebo in Treatment of Patients With Smouldering Systemic, Indolent Systemic or Cutaneous Mastocytosis With Handicap

The objective of this study is to compare the safety and efficacy of masitinib (AB1010) to placebo in patients with mastocytosis with handicap.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This was a prospective, multicenter, randomized, placebo-controlled, parallel-group, phase 3 study, conducted in 15 countries, evaluating the efficacy and safety of masitinib (6 mg/kg/day administered orally in two daily intakes over 24-weeks with a double-blind extension period possible) for the treatment of indolent systemic mastocytosis, smoldering mastocytosis or cutaneous mastocytosis, in patients with mast cells mediator release symptoms that are refractory to conventional symptomatic treatment.

A study protocol amendment restricted enrolment to patients with severe indolent and smoldering systemic mastocytosis. The objective of this phase 3 study was therefore to evaluate masitinib efficacy and safety in severe systemic mastocytosis patients, with or without D816V mutation of c-Kit. The primary objective of the phase 3 study was to detect a statistically significant difference between masitinib (plus optimal concomitant symptomatic treatments) and placebo (plus optimal concomitant symptomatic treatments) in cumulative response on four severe symptoms, referred to also as handicaps.

Study Type

Interventional

Enrollment (Actual)

135

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Amiens, France
        • CHU d'Amiens
      • Bobigny, France
        • Hôpital Avicenne
      • Brest, France
        • CHU de Brest
      • Caen, France
        • CHU de Caen
      • Clermont Ferrand, France, 63000
        • CHU Clermont Ferrand
      • Lille, France
        • Hôpital Claude Huriez
      • Limoges, France
        • CHU Dupuytren
      • Marseille, France
        • Hopital Nord
      • Marseille, France
        • Hôpital Ambroise Paré
      • Nancy, France
        • Hôpital Central
      • Nantes, France
        • CHU Hotel Dieu
      • Nice, France
        • Hopital L'Archet II
      • Paris, France
        • Hopital Necker
      • Paris, France
        • Hopital Tenon
      • Pierre Bénite, France, 69495
        • CHU Lyon Sud
      • Pierre-Bénite, France
        • Centre Hospitalier Lyon Sud
      • Poitiers, France
        • CHU Milétrie
      • Rennes, France
        • CHU Hopital Sud
      • Saint-Etienne, France
        • CHU de Saint-Etienne
      • Toulouse, France
        • Hopital Purpan
      • Tours, France
        • Hôpital Bretonneau
      • Troyes, France
        • Hopital des Hauts Clos
  • United States
    • California
      • Sacramento, California, United States, 95816
        • UC Davis Health System , Department of Dermatology
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patient with one of the following documented mastocytosis as per WHO classification: Smouldering Systemic Mastocytosis, Severe Indolent Mastocytosis
  2. Patient with documented mastocytosis and evaluable disease based upon histological criteria: typical infiltrates of mast cells in a multifocal or diffuse pattern in skin and/or bone marrow biopsy
  3. Patient with documented treatment failure of his/her handicap(s) with at least one of the following therapy used at optimized dose: Anti H1, Anti H2, Proton pump inhibitor, Osteoclast inhibitor, Cromoglycate Sodium, Antileukotriene
  4. Handicapped status defined as at least two of the following handicaps, including at least one among pruritus, flushes, depression and fatigue: pruritus score ≥ 9, number of flushes per week ≥ 8, Hamilton rating scale for depression (HAMD-17) score ≥ 19, number of stools per day ≥ 4, number of mictions per day ≥ 8, Fatigue Impact Scale total score (asthenia) ≥ 75
  5. Patients with OPA ≥ 2 (moderate to intolerable general handicap)
  6. ECOG ≤ 2
  7. Patient with adequate organ function

Exclusion Criteria:

  1. Patient with one of the following mastocytosis: Cutaneous Mastocytosis, Not documented Smouldering Systemic Mastocytosis or Indolent Systemic Mastocytosis, Systemic Mastocytosis with an Associated clonal Hematologic Non Mast cell lineage Disease (SM-AHNMD), Mast cell leukemia (MCL), Aggressive systemic mastocytosis (ASM)
  2. Previous treatment with any Tyrosine Kinase Inhibitor
  3. Patient with recent cardiac history of: Acute coronary syndrome, Acute heart failure, Significant ventricular arrhythmia; patient with cardiac failure class III or IV; Syncope without known aetiology within 3 months, uncontrolled severe hypertension.
  4. Patient with any condition that the physician judges could be detrimental to subjects participating in this study; including any clinically important deviations from normal clinical laboratory values or concurrent medical events Previous treatment
  5. Change in the symptomatic treatment of mastocytosis or administration of any new treatment of mastocytosis within 4 weeks prior to baseline
  6. Treatment with any investigational agent within 4 weeks prior to baseline

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Masitinib & BSC
Masitinib (6 mg/kg/day) administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)
Drug: Masitinib
Masitinib 6 mg/kg/day
Other Names:
  • AB1010
Other: Best Supportive Care
Optimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, proton pump inhibitors (PPI), sodium cromoglicate, antidepressants, leukotriene antagonists, interferon-alpha, 2-CdA, and corticosteroids.
Placebo Comparator: Placebo & BSC
Matching placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)
Drug: Placebo
Matching placebo
Other: Best Supportive Care
Optimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, proton pump inhibitors (PPI), sodium cromoglicate, antidepressants, leukotriene antagonists, interferon-alpha, 2-CdA, and corticosteroids.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative response (4R75%)
Time Frame: 24 weeks
The prospectively declared primary endpoint (4R75%) was cumulative response in at least one of four severe baseline symptoms of mast cell mediator release (pruritus, flushes, depression, or asthenia). Response was defined as a 75% improvement from baseline for any of these four symptoms. Cumulative response was defined as the number of actual responses between weeks 8 and 24, divided by the total number of possible responses over the same treatment period (ie, with five scheduled visits, each patient had a maximum of five to 20 possible responses depending on the number of severe baseline symptoms).
24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative response (3R75%)
Time Frame: 24 weeks
Cumulative response in at least one of three severe baseline symptoms (pruritus, flushes, or depression)
24 weeks
Cumulative response (2R75%)
Time Frame: 24 weeks
Cumulative response in at least one of three severe baseline symptoms (pruritus or flushes)
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AB Science

Investigators

  • Principal Investigator: Olivier Lortholary, MD, PhD, Hopital Necker, Paris, France

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2008

Primary Completion (Actual)

November 1, 2015

Study Completion (Actual)

November 1, 2015

Study Registration Dates

First Submitted

December 22, 2008

First Submitted That Met QC Criteria

December 22, 2008

First Posted (Estimate)

December 23, 2008

Study Record Updates

Last Update Posted (Actual)

December 3, 2019

Last Update Submitted That Met QC Criteria

November 29, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AB06006

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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