| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10011762 |
| E.1.2 | Term | Cystic fibrosis |
| E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To explore the impact of LUM/IVA on disease progression in subjects aged 2 through 5 years with CF, homozygous for F508del |
|
| E.2.2 | Secondary objectives of the trial |
| To explore the relationship between lung clearance index (LCI) and imaging modalities for LUM/IVA in subjects aged 2 through 5 years with CF, homozygous for F508del |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject’s legally appointed and authorized representative (e.g., parent or legal guardian) will sign and date an informed consent form (ICF) and the subject will sign and date an assent form (if applicable).
2. Subject’s legally appointed and authorized representative (e.g., parent or legal guardian) is willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, and other study procedures.
3. Subjects (male and female) will be between the ages of 2 and 5 years, inclusive, on the date of informed consent (and assent, if applicable).
4. Subjects who weigh ≥8 kg without shoes and wearing light clothing at the Screening Visit.
5. Subjects with confirmed diagnosis of CF, defined as:
- a sweat chloride value ≥60 mmol/L by quantitative pilocarpine iontophoresis as documented in the subject’s medical record OR from the sweat chloride test result obtained at the Screening Visit (if an eligible historical sweat chloride result is documented in the subject’s medical record, that result alone [and not the Screening Visit result] may be used to determine eligibility)
AND
- clinical manifestations of CF.
6. Subjects who are homozygous for F508del (genotype to be confirmed at the Screening Visit or as documented in the subject’s medical record).
7. Subjects with stable CF disease as deemed by the investigator at the Screening Visit.
8. Subjects who are willing to remain on a stable CF medication regimen through the Safety Follow-up Visit, if applicable. |
|
| E.4 | Principal exclusion criteria |
1. History of any illness or comorbidity reviewed at the Screening Visit that, in the opinion of the investigator, might confound the results of the study, interfere with or pose an additional risk in conducting the study assessments, or pose an additional risk in administering study drug to the subject. For example, a history of cirrhosis with portal hypertension, or prior allergic reaction to gadolinium (Gd)-based contrast material, or metallic implants incompatible with MRI.
2. Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject (as deemed by the investigator).
3. Any of the following abnormal laboratory values at the Screening Visit:
- Hemoglobin <10 g/dL
- Alanine transaminase (ALT), aspartate transaminase (AST), or total bilirubin >2 × upper limit of normal (ULN)
- Abnormal renal function defined as glomerular filtration rate ≤45 mL/min/1.73 m2 (calculated by the Bedside Schwartz equation)11
4. An acute upper or lower respiratory infection, PEx as defined by the investigator, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug).
5. Any clinically significant "non-CF-related" illness within 2 weeks before Day 1. "Illness" is defined as an acute (serious or nonserious) condition (e.g., gastroenteritis).
6. History of solid organ or hematological transplantation.
7. Ongoing or prior participation in an investigational drug study (including studies investigating LUM and/or IVA) within 30 days of the Screening Visit.
- A washout period of 5 terminal half-lives of the previous investigational study drug, or 30 days, whichever is longer, must elapse before the Screening Visit.
- The duration of the elapsed time may be longer if required by local regulations.
Note: Ongoing participation in a noninterventional study (including observational studies) is permitted.
8. Use of restricted medication or food within specified duration before the first dose of study drug as defined in Section 9.4.
9. Inability of the subject to perform the multiple-breath washout (MBW) assessment at the Screening Visit (Section 11.4.1).
10. History of cataract/lens opacity or evidence of cataract/lens opacity determined to be clinically significant by a licensed ophthalmologist during the ophthalmologic examination (OE) at the Screening Visit. The Screening Visit OE does not need to be repeated if there is documentation of an examination meeting protocol criteria that was conducted within 3 months before the Screening Visit. Subjects with documentation of bilateral lens removal do not need the OE and this criterion does not apply. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Absolute change from baseline in magnetic resonance imaging (MRI) global chest score at Week 48 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- Absolute change from baseline in lung clearance index (LCI)2.5 through Week 48
- Absolute change from baseline in weight-for-age z-score at Week 48
- Absolute change from baseline in stature-for-age z-score at Week 48
- Absolute change from baseline in body mass index (BMI)-for-age z-score at Week 48 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Impact of lumacaftor/ivacaftor on disease progression |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
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