| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Chronic Inflammatory Demyelinating Polyneuropathy | |
| E.1.1.1 | Medical condition in easily understood language | | Inflammation of peripheral nervous system | |
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| 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 | 10077384 | | E.1.2 | Term | Chronic inflammatory demyelinating polyneuropathy | | E.1.2 | System Organ Class | 100000004852 | |
| 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 assess the long-term safety and tolerability of efgartigimod PH20 SC (efgartigimod co-formulated with recombinant human hyaluronidase PH20 [rHuPH20] for subcutaneous [SC] administration) | |
| E.2.2 | Secondary objectives of the trial | - To determine the long-term efficacy
- To evaluate the immunogenicity (antidrug antibodies [ADA]) against efgartigimod during the first 48 week treatment cycle [followed by a safety follow-up period, if applicable])
- To evaluate the pharmacokinetics (PK) of efgartigimod PH20 SC (during the first 48 week treatment cycle [followed by a safety follow-up period, if applicable])
- To evaluate the pharmacodynamic (PD) effect of efgartigimod PH20 SC (ie, immunoglobulin G [IgG] levels)
- To evaluate additional patient-reported outcomes (PROs) (including patient-reported quality of life and satisfaction with treatment)
- To explore self-administration of the treatment
-To explore administration of the treatment by caregivers.
Note that there are other objectives for patients with less frequent than weekly dosing of efgartigimod PH20 SC which are described in Section 11.9 of the protocol. | |
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives | Optional Dosing Frequency Substudy:
The optional dosing frequency substudy offers patients who are stabilized on weekly dosing for at least 12 weeks the option to receive 2 less frequent efgartigimod dosing regimens sequentially (see separate protocol appendix for a dosing frequency substudy). | |
| E.3 | Principal inclusion criteria | 1. Ability to understand the requirements of the trial, provide written informed consent (including consent for the use and disclosure of research-related health information), willingness and ability to comply with the trial protocol procedures (including required trial visits) of this trial.
2. a. Male or female patient with 1 of the following options:
- Have completed the Week-48 visit of Stage B of the ARGX-113-1802 trial and are considered to be eligible for treatment with efgartigimod PH20 SC; or
- Have deteriorated during Stage B of the ARGX-113-1802 trial and are considered to be eligible for treatment with efgartigimod PH20 SC, or
- Have been offered the participation in the OLE trial due to early termination of the ARGX-113-1802 trial (because sufficient events for the primary endpoint analysis of the that trial have been reached and it is stopped) and are considered to be eligible for treatment with efgartigimod PH20 SC treatment; or
- Have completed the Week-48 visit of the previous cycle of the OLE trial and are considered to be eligible to continue with efgartigimod PH20 SC treatment.
Optional Dosing Frequency Substudy: Note that after a minimum period of weekly dosing in this OLE trial, as specified in a separate protocol appendix for a dosing frequency substudy, patients who have a stable clinical condition for at least 12 weeks will be offered the option to receive less frequent dosing to evaluate the maintenance of the clinical condition by administration of efgartigimod PH20 SC 1000 mg at 2 lower dosing frequencies.
3. Women of childbearing potential who have a negative urine pregnancy test at baseline before IMP administration.
4. a. Women of childbearing potential must use an acceptable method of contraception from signing the ICF until the date of the last dose of IMP
5. Inclusion criterion removed via protocol amendment #4 | |
| E.4 | Principal exclusion criteria | 1. Week-48/ED visit in the ARGX-113-1802 trial or the Week-48 visit of the previous OLE participation occurred more than 14 days prior to SD1 of the OLE trial or the start of a new treatment cycle in the OLE trial and more than 21 days since the last dose of IMP.
2. a. Pregnant and lactating women and those intending to become pregnant during the trial.
3. Patients with clinical evidence of other significant serious disease or patients who underwent a recent or have a planned major surgery, or patients who (intend to) use prohibited medications and therapies during the trial, or any other reason which could confound the results of the trial or put the patient at undue risk. | |
| E.5 End points |
| E.5.1 | Primary end point(s) | - Incidence of TEAEs and SAEs by system organ class (SOC) and preferred term (PT).
- Incidence of clinically significant laboratory abnormalities. | |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | TEAEs and SAEs are monitored throughout the entire study duration
Blood sampling for laboratory analysis is taken at every study visit | |
| E.5.2 | Secondary end point(s) | Efficacy;
Change from baseline over time in the following scores and measurements:
− Adjusted INCAT score;
− MRC Sum score;
− 24-item I-RODS disability scores;
− Mean grip strength assessed by Martin vigorimeter;
− TUG score.
Percentage of patients without clinical deterioration over time, defined by adjusted INCAT increase ≥1 point compared to baseline.
Immunogenicity;
- Percentage of patients with and titers of binding antibodies (BAb) towards efgartigimod; and the presence of neutralizing antibodies (NAb) against efgartigimod.
Pharmacokinetics;
- Efgartigimod serum concentrations (during the first 48 week treatment cycle [followed by a safety follow-up period, if applicable])
Pharmacodynamics;
- Changes from baseline over time of serum IgG levels (total)
Additional Patient-reported Outcome;
Change from baseline over time in:
− Health-related quality-of-life questionnaire (EQ-5D-5L);
− Brief Pain Inventory – Short Form (BPI-SF);
− 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9);
− Rasch-transformed-Fatigue Severity Scale (RT-FSS);
− Hospital Anxiety and Depression Scale (HADS).
Percentage of patients performing self-administration over time.
Percentage of patients with treatment administered by caregiver over time. | |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | Efficacy, immunogenicity, pharmacokinetic and pharmacodynamic endpoints are assessed at every study visit
Patient report outcomes are assessed at every study visit with the exception of visit 2 (week 4) | |
| 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 | Yes |
| 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 | |
| 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 | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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 | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| 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 | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 61 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | | Ukraine | | Taiwan | | Canada | | China | | Georgia | | Israel | | Japan | | Russian Federation | | Serbia | | Turkey | | United Kingdom | | United States | | Belgium | | Bulgaria | | Czechia | | Denmark | | France | | Germany | | Hungary | | Italy | | Latvia | | Netherlands | | Poland | | Romania | | Spain | |
| 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 | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
