Pemphigus Foliaceus, Pemphigus Vulgaris
Conditions
Brief summary
This was a prospective, multicenter, open label extension (OLE) trial on the efficacy, safety, patient outcome measures, tolerability, immunogenicity, PK and PD of efgartigimod PH20 SC in adult PV or PF participants, who participated in antecedent trial ARGX-113-1904. This trial provided extension of efgartigimod PH20 SC treatment and retreatment options for participants who had been randomized to efgartigimod PH20 SC treatment arm in the trial ARGX-113-1904, and first treatment of efgartigimod PH20 SC and retreatment options for participants who had been randomized to the placebo arm in trial ARGX-113-1904. The participants could also receive concomitant prednisone therapy. Investigators could increase or decrease the prednisone dose based on protocol-specified criteria. Trial ARGX-113-1905 evaluated the ability to (further) taper prednisone therapy and achieve Clinical Remission (CR) off therapy (CRoff), the ability to achieve CR and CR on minimal therapy (CRmin) for participants who had not yet achieved CR or CRmin, and the ability to treat flare; it also assessed patient outcome measures and the safety, PD, PK and immunogenicity of efgartigimod PH20 SC over the duration of trial. Study duration: Up to 60 weeks for participants who receive IMP administration up to 52 weeks and with a follow-up period of 8 weeks after the last IMP administration
Interventions
BIOLOGICALefgartigimod PH20 SC
Subcutaneous injection of efgartigimod using rHuPH20 (PH20) as a permeation enhancer
DRUGprednisone
Oral prednisone tablets
Sponsors
argenx
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Ability to understand the requirements of the trial, to 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). 2. The participant participated in trial ARGX-113-1904 and completed the study or has the defined criteria for rollover. 3. Contraceptive use by men and women should be consistent with local regulations regarding the methods for contraception for those participating in clinical trials and: 1. Male participants: Male participants must agree to use an acceptable method of contraception as described in the protocol, from signing the ICF until the last dose of the study drug. 2. Female participants Women of childbearing potential (WOCBP) must: * have a negative urine pregnancy test at baseline before the IMP can be administered, * agree to use a highly effective or acceptable contraception method (as described in the protocol), which should be maintained at minimum until after the last dose of IMP
Exclusion criteria
1. Pregnant and lactating women and those intending to become pregnant during the trial. 2. Participants with clinical evidence of other significant serious disease or participants who recently underwent or have planned a major surgery during the period of the trial, or any other condition in the opinion of the investigator, that could confound the results of the trial or put the participant at undue risk. 3. Known hypersensitivity to any of the components of the administered treatments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE) | Up to 60 weeks | Incidence rates were calculated as 100 × n/PYFU. PYFU=participant-years of follow-up. The safety data sets includes participants with pemphigus vulgaris (PV) and pemphigus foliaceus (PF). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Pemphigus Vulgaris (PV) and Pemphigus Foliaceus (PF) Who Achieve CRmin | Up to 60 weeks | CRmin defined as the absence of new lesions and complete healing of established lesions while the participant was receiving prednisone at ≤10 mg/day for at least 8 weeks. |
| Proportion of Participants With Pemphigus Vulgaris (PV) Who Achieve CRmin | Up to 60 weeks | CRmin (complete clinical remission on minimal prednisone therapy) defined as the absence of new lesions and complete healing of established lesions while the participant was receiving prednisone at ≤10 mg/day for at least 8 weeks. |
| Time to DC in Participants With PV and PF | Up to 52 weeks | Disease Control (DC) defined as absence of new lesions and the start of healing of established lesions |
| Time to CRmin in Participants With PV and PF | Up to 52 weeks | CRmin defined as the absence of new lesions and complete healing of established lesions while the participant was receiving prednisone at ≤10 mg/day for at least 8 weeks. |
| Time to CR in Participants With PV and PF | Up to 52 weeks | CR (Complete clinical remission) defined as the absence of new lesions and complete healing of established lesions |
| Time to Flare After CRmin in Participants With PV and PF | Up to 52 weeks | CRmin defined as defined as the absence of new lesions and complete healing of established lesions while the participant was receiving prednisone at ≤10 mg/day for at least 8 weeks. |
| Rate of Treatment Failure in Participants With PV and PF | Up to 52 weeks | The absence of DC with oral prednisone 1.5 mg/kg/day for a minimum of 3 weeks, or absence of DC due to prednisone-related SAE, or flare before CRmin resulting in withdrawal of the participant. |
| Number of Flares in Participants With PV and PF | Up to 60 weeks | A flare is defined as the appearance of 3 or more new lesions in a 4-week period that do not heal spontaneously within 1 week or the extension, of established lesions in a participant who had achieved DC. |
| Normalized Cumulative Prednisone Dose in Participants With PV and PF | Up to 60 weeks | Normalized Cumulative prednisone dose (NCPD, mg/kg/day) is the average daily intake of all weight-adjusted prednisone doses received during the study, taking into account the number of days in study |
| Time to CRoff in Participants With PV and PF | Up to 52 weeks | Complete remission off therapy (CRoff) is defined as the absence of new and established lesions completely healed while the patient is receiving no prednisone therapy for at least 8 weeks. |
Countries
Australia, Bulgaria, China, France, Georgia, Germany, Greece, Hungary, India, Israel, Italy, Japan, Poland, Romania, Russia, Serbia, Spain, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
This study was terminated early based on the lack of observed efficacy in antecedent ARGX-113-1904. A total of 183 participants rolled over from ARGX-113-1904. Of these, 57 participants had a CRmin status (complete remission on minimal prednisone therapy) at rollover of which 34 participants did not receive efgartigimod PH20 SC in this ARGX-113-1905 study.
Pre-assignment details
Two main analysis sets were analyzed in the outcome measures: Roll-over set includes all participants regardless of whether they received efgartigimod PH20 SC treatment during this study. Safety set includes participants who received at least 1 dose of efgartigimod PH20 SC during this study. Additional restrictions to the analysis set might apply in the different outcome measures. These are described in the analysis population descriptions.
Participants by arm
| Arm | Count |
|---|---|
| Efgartigimod-efgartigimod PH20 SC Participants who received efgartigimod PH20 SC in antecedent study ARGX-113-1904. | 123 |
| Placebo-efgartigimod PH20 SC Participants who received placebo PH20 SC in antecedent study ARGX-113-1904. | 60 |
| Total | 183 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Other | 15 | 8 |
| Overall Study | Physician Decision | 7 | 2 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Requires Prohibited Medication | 0 | 1 |
| Overall Study | Study Terminated by Sponsor | 18 | 12 |
| Overall Study | Withdrawal by Subject | 16 | 12 |
Baseline characteristics
| Characteristic | Placebo-efgartigimod PH20 SC | Total | Efgartigimod-efgartigimod PH20 SC |
|---|---|---|---|
| Age, Continuous | 52.4 years STANDARD_DEVIATION 13.02 | 50.8 years STANDARD_DEVIATION 11.97 | 50.1 years STANDARD_DEVIATION 11.4 |
| Race/Ethnicity, Customized Asian | 9 Participants | 49 Participants | 40 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 4 Participants | 7 Participants | 3 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 56 Participants | 176 Participants | 120 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 47 Participants | 128 Participants | 81 Participants |
| Sex: Female, Male Female | 32 Participants | 93 Participants | 61 Participants |
| Sex: Female, Male Male | 28 Participants | 90 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 101 | 1 / 48 |
| other Total, other adverse events | 46 / 101 | 19 / 48 |
| serious Total, serious adverse events | 16 / 101 | 4 / 48 |
Outcome results
Primary
Incidence of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE)
Incidence rates were calculated as 100 × n/PYFU. PYFU=participant-years of follow-up. The safety data sets includes participants with pemphigus vulgaris (PV) and pemphigus foliaceus (PF).
Time frame: Up to 60 weeks
Population: Safety set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Efgartigimod-efgartigimod PH20 SC | Incidence of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE) | Treatment-Emergent Adverse Event (TEAE) | 116.4 number of events x 100/PYFU |
| Efgartigimod-efgartigimod PH20 SC | Incidence of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE) | Adverse Event of Special Interest (AESI) | 72.0 number of events x 100/PYFU |
| Efgartigimod-efgartigimod PH20 SC | Incidence of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE) | Serious Adverse Event (SAE) | 24.5 number of events x 100/PYFU |
| Placebo-efgartigimod PH20 SC | Incidence of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE) | Treatment-Emergent Adverse Event (TEAE) | 113.0 number of events x 100/PYFU |
| Placebo-efgartigimod PH20 SC | Incidence of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE) | Adverse Event of Special Interest (AESI) | 69.3 number of events x 100/PYFU |
| Placebo-efgartigimod PH20 SC | Incidence of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE) | Serious Adverse Event (SAE) | 14.6 number of events x 100/PYFU |
Secondary
Normalized Cumulative Prednisone Dose in Participants With PV and PF
Normalized Cumulative prednisone dose (NCPD, mg/kg/day) is the average daily intake of all weight-adjusted prednisone doses received during the study, taking into account the number of days in study
Time frame: Up to 60 weeks
Population: Roll-over set - For participants that do not achieve CRmin (or CRoff), NCPD until CRmin (or CRoff) is not calculated
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Efgartigimod-efgartigimod PH20 SC | Normalized Cumulative Prednisone Dose in Participants With PV and PF | 0.212 mg/kg/day | Standard Deviation 0.2018 |
| Placebo-efgartigimod PH20 SC | Normalized Cumulative Prednisone Dose in Participants With PV and PF | 0.241 mg/kg/day | Standard Deviation 0.2401 |
Secondary
Number of Flares in Participants With PV and PF
A flare is defined as the appearance of 3 or more new lesions in a 4-week period that do not heal spontaneously within 1 week or the extension, of established lesions in a participant who had achieved DC.
Time frame: Up to 60 weeks
Population: Roll-over set - Only participants who achieved DC were considered for the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Efgartigimod-efgartigimod PH20 SC | Number of Flares in Participants With PV and PF | 0.8 Flares | Standard Deviation 1.03 |
| Placebo-efgartigimod PH20 SC | Number of Flares in Participants With PV and PF | 0.7 Flares | Standard Deviation 0.79 |
Secondary
Proportion of Participants With Pemphigus Vulgaris (PV) and Pemphigus Foliaceus (PF) Who Achieve CRmin
CRmin defined as the absence of new lesions and complete healing of established lesions while the participant was receiving prednisone at ≤10 mg/day for at least 8 weeks.
Time frame: Up to 60 weeks
Population: Safety set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Efgartigimod-efgartigimod PH20 SC | Proportion of Participants With Pemphigus Vulgaris (PV) and Pemphigus Foliaceus (PF) Who Achieve CRmin | 55 Participants |
| Placebo-efgartigimod PH20 SC | Proportion of Participants With Pemphigus Vulgaris (PV) and Pemphigus Foliaceus (PF) Who Achieve CRmin | 26 Participants |
Secondary
Proportion of Participants With Pemphigus Vulgaris (PV) Who Achieve CRmin
CRmin (complete clinical remission on minimal prednisone therapy) defined as the absence of new lesions and complete healing of established lesions while the participant was receiving prednisone at ≤10 mg/day for at least 8 weeks.
Time frame: Up to 60 weeks
Population: Safety set - Participants with PV
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Efgartigimod-efgartigimod PH20 SC | Proportion of Participants With Pemphigus Vulgaris (PV) Who Achieve CRmin | 47 Participants |
| Placebo-efgartigimod PH20 SC | Proportion of Participants With Pemphigus Vulgaris (PV) Who Achieve CRmin | 22 Participants |
Secondary
Rate of Treatment Failure in Participants With PV and PF
The absence of DC with oral prednisone 1.5 mg/kg/day for a minimum of 3 weeks, or absence of DC due to prednisone-related SAE, or flare before CRmin resulting in withdrawal of the participant.
Time frame: Up to 52 weeks
Population: Safety set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Efgartigimod-efgartigimod PH20 SC | Rate of Treatment Failure in Participants With PV and PF | 3 Participants |
| Placebo-efgartigimod PH20 SC | Rate of Treatment Failure in Participants With PV and PF | 1 Participants |
Secondary
Time to CR in Participants With PV and PF
CR (Complete clinical remission) defined as the absence of new lesions and complete healing of established lesions
Time frame: Up to 52 weeks
Population: Safety set - Participants with status CR at the roll-over visit were not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efgartigimod-efgartigimod PH20 SC | Time to CR in Participants With PV and PF | 66.0 Days |
| Placebo-efgartigimod PH20 SC | Time to CR in Participants With PV and PF | 71.0 Days |
Secondary
Time to CRmin in Participants With PV and PF
CRmin defined as the absence of new lesions and complete healing of established lesions while the participant was receiving prednisone at ≤10 mg/day for at least 8 weeks.
Time frame: Up to 52 weeks
Population: Safety set - Participants with status CRmin at the roll-over visit were not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efgartigimod-efgartigimod PH20 SC | Time to CRmin in Participants With PV and PF | 229.0 days |
| Placebo-efgartigimod PH20 SC | Time to CRmin in Participants With PV and PF | 169.0 days |
Secondary
Time to CRoff in Participants With PV and PF
Complete remission off therapy (CRoff) is defined as the absence of new and established lesions completely healed while the patient is receiving no prednisone therapy for at least 8 weeks.
Time frame: Up to 52 weeks
Population: Safety set - Participants with status CRoff at the roll-over visit were not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efgartigimod-efgartigimod PH20 SC | Time to CRoff in Participants With PV and PF | NA days |
| Placebo-efgartigimod PH20 SC | Time to CRoff in Participants With PV and PF | NA days |
Secondary
Time to DC in Participants With PV and PF
Disease Control (DC) defined as absence of new lesions and the start of healing of established lesions
Time frame: Up to 52 weeks
Population: Safety set - Participants with status DC at the roll-over visit were not included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efgartigimod-efgartigimod PH20 SC | Time to DC in Participants With PV and PF | 8.5 days |
| Placebo-efgartigimod PH20 SC | Time to DC in Participants With PV and PF | 15.0 days |
Secondary
Time to Flare After CRmin in Participants With PV and PF
CRmin defined as defined as the absence of new lesions and complete healing of established lesions while the participant was receiving prednisone at ≤10 mg/day for at least 8 weeks.
Time frame: Up to 52 weeks
Population: Safety set - Only participants who achieved CRmin were considered for the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efgartigimod-efgartigimod PH20 SC | Time to Flare After CRmin in Participants With PV and PF | 339.0 days |
| Placebo-efgartigimod PH20 SC | Time to Flare After CRmin in Participants With PV and PF | 168.0 days |