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

NCT02615938 | Terminated Phase 2 Results DMC

• 1 other identifier: EudratCT:2013-003714-40
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 9

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.

Conditions

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

Keywords

Childhood ILD; Fibrosing lung disease

Outcome Measures

Primary Outcomes (1)

• Change in Oxygenation (Presence or Absence of Response to Treatment) Defined as Change in O2 Saturation >=5%, or Change in Respiratory Rate >=20%, or Change in Respiratory Support Necessary

  O2 saturation measured after 5 min at rest and after withdrawal of oxygen if supplied. Change in Oxygenation (presence or absence of response to treatment) defined as change in O2 saturation \>=5%, or change in respiratory rate \>=20%, or change in respiratory support necessary

  Start block: A,B after 4 and C,D after 8 weeks; Stop block: E,F after 12 and G,H after 24 weeks

Secondary Outcomes (11)

• Change in Oxygenation (Presence or Absence of Response to Treatment) Defined as Change in O2 Saturation >=3%, or Change in Respiratory Rate >=20%, or Change in Respiratory Support Necessary

  Start block: A,B after 4 and C,D after 8 weeks; Stop block: E,F after 12 and G,H after 24 weeks

• Change of O2-sat in Room Air (%)

  Start block: A,B after 4 and C,D after 8 weeks; Stop block: E,F after 12 and G,H after 24 weeks

• Change of Respiratory Rate in Room Air (Breaths/Min)

  Start block: A,B after 4 and C,D after 8 weeks; Stop block: E,F after 12 and G,H after 24 weeks

• Change of Quality of Life (chILD Specific)

  Start block: A,B after 4 and C,D after 8 weeks; Stop block: E,F after 12 and G,H after 24 weeks

• Change of Quality of Life (Total Score)

  Start block: A,B after 4 and C,D after 8 weeks; Stop block: E,F after 12 and G,H after 24 weeks

Study Arms (4)

Start HCQ block Verum

EXPERIMENTAL

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.

Drug: Hydroxychloroquine sulfate

Start HCQ block Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Stop HCQ block Verum

EXPERIMENTAL

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.

Drug: Hydroxychloroquine sulfate

Stop HCQ block Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

Hydroxychloroquine sulfate DRUG

Apply drug to modify lysosomal pH

Also known as: Quensyl

Start HCQ block Verum; Stop HCQ block Verum

Placebo OTHER

Apply Placebo not to modify lysosomal pH

Also known as: no other name

Start HCQ block Placebo; Stop HCQ block Placebo

Eligibility Criteria

• Age: 3 Weeks - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• No major changes in other medications between Visit 1 and 2
• Diagnosis of chronic (≥ 3 wks of duration) diffuse parenchymal lung disease (DPLD = chILD), defined in at least one of the following ways:
• 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.
• chILD histologically diagnosed
• Chronic pneumonitis of infancy (CPI)
• Desquamative interstitial pneumonia (DIP)
• Lipoid pneumonitis / Cholesterol pneumonia
• Nonspecific interstitial pneumonia (NSIP)
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Matthias Griese: lead

Study Sites (9)

Universitätsklinik für Kinder- und Jugendmedizin Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Klinikum der Universität München, Haunersches Kinderspital

München, Bavaria, 80337, Germany

Location

Universitätsklinikum Frankfurt, Pneumologie, Allergologie, Mukoviszidose

Frankfurt am Main, Hesse, 60590, Germany

Location

Justus-Liebig-Universität, Allgemeine Pädiatrie u. Neonatologie

Giessen, Hesse, 35385, Germany

Location

Medizinische Hochschule Hannover

Hanover, Lower Saxony, 30625, Germany

Location

St. Joseph- und St. Elisabeth Hospital gGmbH

Bochum, North Rhine-Westphalia, 44791, Germany

Location

Uniklinikum Essen, Pädiatrische Pneumologie

Essen, North Rhine-Westphalia, 45122, Germany

Location

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

Leipzig, Saxony, 04103, Germany

Location

Charité Berlin, Klinik für Pädiatrie

Berlin, 13353, Germany

Location

Related Publications (3)

• 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.

  PMID: 32245508 BACKGROUND

• 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.

  PMID: 25491573 BACKGROUND

• 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.

  PMID: 35871071 RESULT

MeSH Terms

Conditions

Lung Diseases, Interstitial

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Limitations include not reaching the target number of participants. As this was the first randomized controlled trial in fibrosing chILD performed ever, the study was exploratory and there was no formal sample size calculation. Including more patients was prevented by interference with an authority inspection, COVID19 pandemic and the ultra-rare conditions targeted. See for more details Orphanet J Rare Dis. 2022 Jul 23;17(1):289. doi: 10.1186/s13023-022-02399-2. PMID: 35871071.

Results Point of Contact

• Title: Prof. Matthias Griese
• Organization: LMU/ Haunersches Kinderspital

matthias.griese@med.uni-muenchen.de

+498944000

Study Officials

• Matthias Griese

  Hauner Children´s Hospital, LMU

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo-bitter taste, same color and form capsule. Verum-same color, form capsule as placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med.

Model Details: Goal of the study was to include all chILD patients who are planned to be, or are actively being, treated with HCQ. The character of this study is explorative. It was designed to closely accommodate the current clinical care situation.The study was an explorative, prospective, randomized, doubleblind, placebo-controlled investigation of HCQ in chILD and was one of the first investigator-initiated trials in this condition. The study contained two different study blocks, a START and a STOP block, which could be initiated in any sequence. Each patient can participate in each block only once. In the START block, subjects were randomized to parallel groups for 4 weeks treatment, then the placebo group switched to the active drug. In the STOP block, subjects taking HCQ were randomized into parallel groups (placebo or HCQ).

Study Record Dates

• First Submitted: November 8, 2015
• First Posted: November 26, 2015
• Study Start: August 21, 2015
• Primary Completion: June 27, 2019
• Study Completion: September 9, 2020
• Last Updated: December 3, 2025
• Results First Posted: December 3, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (9)