E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Autosomal dominant polycystic kidney disease |
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E.1.1.1 | Medical condition in easily understood language |
Autosomal dominant polycystic kidney disease |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036046 |
E.1.2 | Term | Polycystic kidney, autosomal dominant |
E.1.2 | System Organ Class | 100000004850 |
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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 characterize the effect of GLPG2737 on growth in total kidney volume (TKV) compared to placebo.
- To evaluate the safety and tolerability of oral doses of GLPG2737 compared to placebo.
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E.2.2 | Secondary objectives of the trial |
- To characterize the effect of GLPG2737 on renal function (estimated glomerular filtration rate; eGFR) compared to placebo.
- To characterize the pharmacokinetics (PK) of oral doses of GLPG2737 and its major metabolite G1125498 (M4) using population PK analyses. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Main inclusion criteria for the double-blind period of the study:
1. Male and female subject aged 18 to 50 years, inclusive.
2. Documented diagnosis of typical ADPKD, using the Ravine criteria.
3. Rapidly progressive disease, defined as presence of all of the following:
-TKV >750 mL, as determined on imaging not older than 5 years before screening. If historical imaging is not available or older than 5 years, imaging can be performed during the screening period according to local clinical practice (i.e. echography, magnetic resonance imaging [MRI]).
-Mayo ADPKD Classification Classes 1C to 1E.
4. eGFR at screening between 30-90 mL/min/1.73 m2 for subjects aged 18 to 40 years (inclusive), and between 30-60 mL/min/1.73 m2 for subjects aged 40 to 50 years.
5. Blood pressure ≤ 150/90 mmHg. In case the subject is treated for hypertension, he/she should be on a stable treatment regimen of antihypertensive therapy for at least 8 weeks prior to the screening visit, and during the screening period.
Main inclusion criteria for the open-label extension period of the study:
1. Male and female subjects who completed the 52-week double-blind
treatment period on IP.
2. Subject, according to the investigator's judgment, may benefit from
long-term treatment with GLPG2737.
Reference is made to the protocol for a complete overview of the inclusion criteria. |
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E.4 | Principal exclusion criteria |
Main exclusion criteria for the double-blind period of the study:
1. Congenital absence of 1 kidney, or subject had a previous nephrectomy or has a transplanted kidney or a transplantation is planned in the foreseeable future.
2. Administration of polycystic kidney disease-modifying agents (e.g.
tolvaptan, somatostatin analogues) or interventions (such as cyst
aspiration or cyst fenestration) within 12 weeks prior to the screening
visit and during the screening period. In case tolvaptan is not being
administered, this should be because of e.g. non-availability, intolerance,
or physician's clinical judgment.
3. Any condition or circumstances that, in the opinion of the investigator, may make a subject unlikely or unable to complete the study or comply with study procedures and requirements (e.g. unable to undergo MRI. For example subject's weight exceeds weight capacity of the MRI, ferromagnetic metal prostheses, aneurysm clips, severe claustrophobia, etc.).
Main exclusion criterion for the open-label extension period of the study:
1. Clinically significant abnormalities detected on 12-lead ECG of either
rhythm or conduction, QTcF >450 ms, or long QT syndrome.
Reference is made to the protocol for a complete overview of the
exclusion criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Mean percent change from baseline of height-adjusted TKV (htTKV).
- Frequency and severity of treatment-emergent adverse events (TEAEs), treatment-emergent serious AEs (SAEs), and TEAEs leading to treatment discontinuation.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Various timepoints throughout the trial from baseline until the end of the
double-blind period as specified in the protocol. |
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E.5.2 | Secondary end point(s) |
- Mean change from baseline estimated GFR (eGFR).
- Estimated exposure (area under the curve [AUC], maximum plasma concentration [Cmax]), based on population PK analyses of GLPG2737 and its major metabolite M4.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Various timepoints throughout the trial from baseline until the end of the
double-blind period as specified in the protocol. |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 | Yes |
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
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The end of the study (EoS) is reached when the last follow-up visit (i.e.
Week 112 of the open-label extension (OLE) period), as planned
according to the Schedule of Activities of the last subject is performed. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |