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Trial record 1 of 1 for:    NCT02615938
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Hydroxychloroquin (HCQ) in Pediatric Interstitial Lung Disease (ILD) (HCQ-chILD-EU)

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: NCT02615938
Recruitment Status : Suspended (Correction of inspection findings)
First Posted : November 26, 2015
Last Update Posted : September 10, 2019
Sponsor:
Information provided by (Responsible Party):
Matthias Griese, Ludwig-Maximilians - University of Munich

Tracking Information
First Submitted Date  ICMJE November 8, 2015
First Posted Date  ICMJE November 26, 2015
Last Update Posted Date September 10, 2019
Study Start Date  ICMJE April 2015
Estimated Primary Completion Date April 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 19, 2018)
Change of Oxygenation [ Time Frame: Start HCQ block: 28 and 56 days; Stop HCQ block: 84 days ]
Start HCQ block: relative Change Trial day 1 through day 28 and relative Change day 28 to day 56; Change active compound compared to Change Placebo. Stop HCQ block: Relative change trail day 1 through day 84: change active compound compared to change Placebo.
Original Primary Outcome Measures  ICMJE
 (submitted: November 24, 2015)
  • Change of Oxygen Saturation [ Time Frame: Baseline - 28 days ]
    Start HCQ block
  • Change of O2-flow [ Time Frame: Baseline - 28 days ]
    Start HCQ block
  • Change of Oxygenation index [ Time Frame: Baseline - 28 days ]
    Start HCQ block
  • Change of Oxygen Saturation [ Time Frame: 28 days - 56 days ]
    Start HCQ block
  • Change of O2-flow [ Time Frame: 28 days - 56 days ]
    Start HCQ block
  • Change of Oxygenation index [ Time Frame: 28 days - 56 days ]
    Start HCQ block
  • Change of Oxygen Saturation [ Time Frame: Baseline - 84 days ]
    Stop HCQ block
  • Change of O2-flow [ Time Frame: Baseline - 84 days ]
    Stop HCQ block
  • Change of Oxygenation index [ Time Frame: Baseline - 84 days ]
    Stop HCQ block
Change History Complete list of historical versions of study NCT02615938 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 19, 2018)
  • Change of Oxygen Saturation [ Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days ]
    (O2-sat, in room air) (only absolute, as relative already Primary outcome)
  • Change of Respiratory rate [ Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days ]
    (RR, in room air) (relative and absolute)
  • Change of Retraction, Coughing [ Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days ]
    (yes/no)
  • Change of Lab values [ Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days ]
    (GOT, Creatinine, gGT, blood count, differential, LDH, potassium, steady state drug level)
  • Change of Oxygen demand [ Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days ]
    in room air, on Os-supplement or O2 flow
  • Change of QoL [ Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days ]
    (PedsQl™ generic and chILD specific module)
  • Change of Health economics [ Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days ]
    specific questionaire
  • Change of Overall survival [ Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days ]
    death or not
  • Change of Weight to Height ratio [ Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days ]
    Weight measured in kg and Height measured in cm
  • Cumulative amounts of Steroid equivalents [ Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days ]
    Clinical course of lung disease (since last visit): Healthy/ Sick-better/ Sick-same/ Sick-worse/ Patient died
  • Change of x-ray [ Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days ]
    if x-ray were done
  • Change of pO2, pCO2 [ Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days ]
    (capillary, in room air)
  • Change of Pulmonary exacerbation [ Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days ]
    (since last visit)
  • Change of Forced vital capacity [ Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days ]
    measured by spirometry or bodyplethysmography; If > 5y old (If a child ≤ 5 years is already able to perform the listed investigations (spirometry or bodyplethysmography), these should also be performed and documented at the discretion of the investigator.)
  • Number of abnormal changes in Electrocardiographie (ECG) [ Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days ]
    measured on start and end of trial
  • Change of 6 minute walking distance (6MWT) (in meter) [ Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days ]
    O2-saturation will be measured before and after 6MWT
  • Change of Borg Scale [ Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days ]
    Measured after 6MWT
  • Number of subjects with ophthalmologic abnormalities [ Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days ]
    Ophthalmologic review on start and end of trial
  • Number of Treatment related advers events [ Time Frame: Start HCQ block: 28 days; Stop HCQ block: 84 days ]
    measured on each visit
Original Secondary Outcome Measures  ICMJE
 (submitted: November 24, 2015)
  • Change of Forced vital capacity [ Time Frame: Visit 2 - 28 days ]
    Start HCQ block
  • Change of Forced vital capacity [ Time Frame: Visit - 84 days ]
    Stop HCQ block
  • Number of subjects with opthalmologic abnormalities [ Time Frame: Visit 2 - 28 days ]
    Start HCQ block
  • Lab values (GOT/GPT/Crea/BUN/CK/GGT/LDH/BB/DIFF/drug level /glucose) [ Time Frame: Visit 2 - 28 days ]
    Start HCQ block
  • Lab values (GOT/GPT/Crea/BUN/CK/GGT/LDH/BB/DIFF/drug level /glucose) [ Time Frame: Visit - 84 days ]
    Stop HCQ block
  • Change of QoL (PedsQl™ generic and chILD specific module) [ Time Frame: Visit 2 - 28 days ]
    Start HCQ block
  • Change of QoL (PedsQl™ generic and chILD specific module) [ Time Frame: Visit - 84 days ]
    Stop HCQ block
  • Overall survival [ Time Frame: Visit 2 - 28 days ]
    Start HCQ block
  • Overall survival [ Time Frame: Visit - 84 days ]
    Stop HCQ block
  • Change of Weight for height [ Time Frame: Visit 2 - 28 days ]
    Start HCQ block
  • Change of Weight for height [ Time Frame: Visit - 84 days ]
    Stop HCQ block
  • Cumulative amounts of Steroid equivalents [ Time Frame: Visit 2 - 28 days ]
    Start HCQ block
  • Cumulative amounts of Steroid equivalents [ Time Frame: Visit - 84 days ]
    Stop HCQ block
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hydroxychloroquin (HCQ) in Pediatric Interstitial Lung Disease (ILD)
Official Title  ICMJE Hydroxychloroquine in Pediatric ILD: START Randomized Controlled in Parallel-group, Then Switch Placebo to Active Drug, and STOP Randomized Controlled in Parallel-Group to Evaluate the Efficacy and Safety of Hydroxychloroquine (HCQ)
Brief Summary This is an exploratory Phase 2a, randomized, double-blind, placebo-controlled, parallel-group, multinational study investigating the initiation or withdrawal of hydroxychloroquine in subjects with chILD.
Detailed Description This study is an explorative, prospective, randomized, double-blind, placebo controlled investigation of hydroxychloroquine (HCQ) in pediatric ILD. The treatments are organized in START and STOP blocks, which can be initiated in sequence, as needed by the subjects. Each patient can participate in each block only once. In the START block subjects are randomized to parallel-groups, then the placebo group is switched to active drug. In the STOP block, subjects on HCQ are randomized into parallel-groups treated with placebo or HCQ to investigate the withdrawal of HCQ for assessment of its efficacy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Interstitial Lung Disease
  • Diffuse Parenchymal Lung Disease
  • Children´s Interstitial Lung Disease
Intervention  ICMJE
  • Drug: Hydroxychloroquine sulfate
    Apply drug to modify lysosomal pH
    Other Name: Quensyl
  • Other: Placebo
    Apply Placebo not to modify lysosomal pH
    Other Name: no other name
Study Arms  ICMJE
  • Experimental: Start HCQ block Verum
    During trial: Hydroxychloroquine Sulfate (HCQ, Quensyl) in a loading dose of 10 mg/kg bw/d, p.o., one daily dose in the evening for 7 days, then reduction to 6,5 mg/kg bw/d for 3 weeks; the maximum daily dose is 400mg.
    Intervention: Drug: Hydroxychloroquine sulfate
  • Placebo Comparator: Start HCQ block Placebo
    At the beginning of the trial: Placebo for 4 weeks then Hydroxychloroquine Sulfate (HCQ, Quensyl) in a loading dose of 10 mg/kg bw/d, p.o., one daily dose in the evening for 7 days, then reduction to 6,5 mg/kg bw/d for 3 weeks; the maximum daily dose is 400mg.
    Intervention: Other: Placebo
  • Experimental: Stop HCQ block Verum
    Individual dose, usually Hydroxychloroquine Sulfate (HCQ, Quensyl) 6-10 mg/kg bw/d, p.o., one daily dose in the evening; the maximum daily dose is 400 mg. The dose, on which the patient is included into the trial, should be continued for 3 months. After therapy of 3 months the medication will be stopped. The patients will be followed up for additional 3 months.
    Intervention: Drug: Hydroxychloroquine sulfate
  • Placebo Comparator: Stop HCQ block Placebo
    Patients will receive Placebo for 3 months and will be followed up for additional 3 months.
    Intervention: Other: Placebo
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 Suspended
Estimated Enrollment  ICMJE
 (submitted: November 24, 2015)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2025
Estimated Primary Completion Date April 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  1. Patients should be clinically stable during baseline (between Visit 1 and 2) for inclusion into the study

    1. To determine this, attending physicians can use SpO2 in room air for patients on room air or on O2-supplement; the absolute difference on SpO2 is expected not to be ≥ 5% between Visit 1 and 2. For patients on respiratory support, the summary key parameters should not change ≥ 20% between Visit 1 and 2 and
    2. No major changes in other medications between Visit 1 and 2
  2. Mature newborn ≥ 37 weeks of gestation, age ≥ 3 wks and <2y or Infants and children (≥2y and < 18y) or Adults (≥18 and ≤30y) or Previously preterm (≤ 37 weeks of gestation) babies or children and adults of all ages if chILD genetically diagnosed (see inclusion criterion 3.)
  3. Diagnosis of chronic (≥ 3 wks of duration) diffuse parenchymal lung disease (DPLD = chILD), defined in at least one of the following ways:

    1. chILD genetically diagnosed Surfactant dysfunction disorders including patients with mutations in SFTPC, SFTPB, ABCA3, TTF1 (Nkx2-1), further extremely rare entities with specific mutations, for example in TBX4, NPC2, NPC1, NPB, COPA, LRBA and other genes. In this case, also previously preterm (≤ 37 weeks of gestation) babies or children and adults of all ages can be included into the study.
    2. chILD histologically diagnosed

      • Chronic pneumonitis of infancy (CPI)
      • Desquamative interstitial pneumonia (DIP)
      • Lipoid pneumonitis / Cholesterol pneumonia
      • Nonspecific interstitial pneumonia (NSIP)
      • PAP after the exclusion of mutations in GMCSF-Ra/b and GMCSF autoantibodies*
      • Usual interstitial pneumonia (UIP)
      • Follicular bronchitis/bronchiolitis/Lymphocytic interstitial pneumonia (LIP)
      • Storage disease with primary pulmonary involvement (e.g. Niemann Pick)
      • Hermansky-Pudlak Syndrome
      • Idiopathic pulmonary haemorrhage (haemosiderosis)*
      • Other histology diagnosing chILD, in particular combination of the above pattern, but not exclusively
  4. Start block: no HCQ treatment in the last 12 weeks Stop block: stable HCQ treatment for at least the last 12 weeks
  5. Ability of subject or/and legal representatives to understand character and individual consequences of clinical trial.
  6. Signed and dated informed consent of the subject (if subject has the ability) and the representatives (of underaged children) must be available before start of any specific trial procedures.

(*may be diagnosed in the absence of a lung biopsy by characteristic lung lavage cytology (PAS stain, Fe stain), CT pattern or autoantibodies (gliadin, endomysium; cANCA) and clinical course.)

Exclusion criteria:

Subjects presenting with any of the following criteria will not be included in the trial:

  • chILD primarily related to developmental disorders
  • chILD primarily related to growth abnormalities reflecting deficient alveolarisation
  • chILD related to chronic aspiration
  • chILD related to immunodeficiency
  • chILD related to abnormalities in lung vessel structure
  • chILD related to organ transplantation/organ rejection/GvHD
  • chILD related to recurrent infections
  • Acute severe infectious exacerbations
  • Known hypersensitivity to HCQ, or other ingredients of the tablets (lactose-monohydrate, povidone, maize starch, magnesium stearate, hypromellose, macrogol or titanium dioxide (E 171), silicon dioxide or mannitol), to sucrose-octaacetate or sodium saccharine.
  • Proven retinopathy or maculopathy
  • Glucose-6-phosphate-dehydrogenase deficiency resulting in favism or hemolytic anemia
  • Myasthenia gravis
  • Hematopoetic disorders
  • Pregnancy and lactation (Women with childbearing potential have to practice a medically accepted contraception during trial and till three months after the end of the treatment with HCQ, and a negative pregnancy test (serum or urine) should be existent on Visit 1, if girls of childbearing age and only if sexual relations are known or probable. It is at the discretion and responsibility of the attending physician to decide, whether a pregnancy test is necessary or not. Reliable contraception are systematic contraceptives (oral, implant, injection). Women that are sterile by surgery can participate in the trial. At the discretion of the investigator, sexual abstinence is also accepted as contraceptive method. Girls after menarche have to receive a counselling about birth control methods in presence of at least one parent, which has to be documented in the patient notes.
  • Participation in other clinical trials during the present clinical trial or not beyond the time of 4 half-lives of the medication used, at least one week.
  • Hereditary galactose intolerance, lactase deficiency or glucose-galactose- malabsorption
  • Renal insufficiency at screening, defined as glomerular filtration rate (GFR)

    • < 40 mL/min/1.73 m2 in patients age 3 to 8 weeks
    • < 60 mL/min/1.73 m2 in patients ≥ 8 weeks of age (KDIGO guideline 2012, K/DOQI guideline 2002)
  • Liver disease, gastrointestinal disorder, haematological disorder, epilepsy or other neurological disorder, psoriasis, porphyria at the discretion of the treating physician
  • Simultaneous prescription of other potentially nephrotoxic or hepatotoxic medication at the discretion of the treating physician
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 99 Years   (Child, 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 Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02615938
Other Study ID Numbers  ICMJE EudratCT:2013-003714-40
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Matthias Griese, Ludwig-Maximilians - University of Munich
Study Sponsor  ICMJE Matthias Griese
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Matthias Griese, Prof., MD Pediatric Pneumology, Ludwig-Maximilians-University Munich
Principal Investigator: Elias Seidl, MD Pediatric Pneumology, Ludwig-Maximilians University Munich
PRS Account Ludwig-Maximilians - University of Munich
Verification Date September 2019

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