Hydroxychloroquine (HCQ) in Pediatric Interstitial Lung Disease (ILD)

NCT ID: NCT02615938

Last Updated: 2025-12-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-21
• Study Completion Date: 2020-09-09

Brief Summary

This is an exploratory Phase 2, 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.

Conditions

Interstitial Lung Disease; Diffuse Parenchymal Lung Disease; Children´s Interstitial Lung Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Start HCQ block Verum

4 weeks of Hydroxychloroquine Sulfate (HCQ, Quensyl) in a loading dose of 10 mg/kg bw/d, p.o., once 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 400 mg.

Then 4 weeks Hydroxychloroquine Sulfate (HCQ, Quensyl). First week loading dose 10 mg/kg bw/d, p.o., once daily in the evening, followed by 6.5 mg/kg bw/d for 3 weeks.

Group Type: EXPERIMENTAL

Hydroxychloroquine sulfate

Intervention Type: DRUG

Apply drug to modify lysosomal pH

Start HCQ block Placebo

4 weeks of Placebo 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 400 mg.

Then 4 weeks Hydroxychloroquine Sulfate (HCQ, Quensyl). First week loading dose 10 mg/kg bw/d, p.o., once daily in the evening, followed by 6.5 mg/kg bw/d for 3 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Apply Placebo not to modify lysosomal pH

Stop HCQ block Verum

Individual dose of Hydroxychloroquine Sulfate (HCQ, Quensyl) 6-10 mg/kg bw/d, p.o., once daily in the evening; the maximum daily dose is 400 mg. The dose on which the patient was included into the trial was continued for 3 months. Then the medication was stopped and the patient followed for additional 3 months.

Group Type: EXPERIMENTAL

Hydroxychloroquine sulfate

Intervention Type: DRUG

Apply drug to modify lysosomal pH

Stop HCQ block Placebo

Individual dose of Placebo 6-10 mg/kg bw/d, p.o., once daily in the evening; the maximum daily dose is 400 mg. The dose on which the patient was included into the trial was continued for 3 months. Then the medication was stopped and the patient wo received HCQ will be followed up for additional 3 months with no medication.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Apply Placebo not to modify lysosomal pH

Interventions

Hydroxychloroquine sulfate

Apply drug to modify lysosomal pH

Intervention Type: DRUG

Placebo

Apply Placebo not to modify lysosomal pH

Intervention Type: OTHER

Other Intervention Names

Quensyl; no other name

Eligibility Criteria

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

• Minimum Eligible Age: 3 Weeks
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Matthias Griese

OTHER

Sponsor Role: lead

Responsible Party

Matthias Griese

Prof. Dr. med.

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Matthias Griese

Role: PRINCIPAL_INVESTIGATOR

Hauner Children´s Hospital, LMU

Locations

Universitätsklinik für Kinder- und Jugendmedizin Tübingen

Tübingen, Baden-Wurttemberg, Germany

Klinikum der Universität München, Haunersches Kinderspital

München, Bavaria, Germany

Universitätsklinikum Frankfurt, Pneumologie, Allergologie, Mukoviszidose

Frankfurt am Main, Hesse, Germany

Justus-Liebig-Universität, Allgemeine Pädiatrie u. Neonatologie

Giessen, Hesse, Germany

Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

St. Joseph- und St. Elisabeth Hospital gGmbH

Bochum, North Rhine-Westphalia, Germany

Uniklinikum Essen, Pädiatrische Pneumologie

Essen, North Rhine-Westphalia, Germany

Klinik u. Poliklinik für Kinder- u. Jugendmedizin der Universität Leipzig

Leipzig, Saxony, Germany

Charité Berlin, Klinik für Pädiatrie

Berlin, , Germany

Countries

Germany

References

Griese M, Kohler M, Witt S, Sebah D, Kappler M, Wetzke M, Schwerk N, Emiralioglu N, Kiper N, Kronfeld K, Ruckes C, Rock H, Anthony G, Seidl E. Prospective evaluation of hydroxychloroquine in pediatric interstitial lung diseases: Study protocol for an investigator-initiated, randomized controlled, parallel-group clinical trial. Trials. 2020 Apr 3;21(1):307. doi: 10.1186/s13063-020-4188-4.

Reference Type: BACKGROUND

PMID: 32245508 (View on PubMed)

Braun S, Ferner M, Kronfeld K, Griese M. Hydroxychloroquine in children with interstitial (diffuse parenchymal) lung diseases. Pediatr Pulmonol. 2015 Apr;50(4):410-9. doi: 10.1002/ppul.23133. Epub 2014 Dec 9.

Reference Type: BACKGROUND

PMID: 25491573 (View on PubMed)

Griese M, Kappler M, Stehling F, Schulze J, Baden W, Koerner-Rettberg C, Carlens J, Prenzel F, Nahrlich L, Thalmeier A, Sebah D, Kronfeld K, Rock H, Ruckes C; HCQ-study group; Wetzke M, Seidl E, Schwerk N. Randomized controlled phase 2 trial of hydroxychloroquine in childhood interstitial lung disease. Orphanet J Rare Dis. 2022 Jul 23;17(1):289. doi: 10.1186/s13023-022-02399-2.

Reference Type: RESULT

PMID: 35871071 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

EudratCT:2013-003714-40

Identifier Type: -

Identifier Source: org_study_id