ADDRESS: A Study to Assess the Efficacy and Safety of a Subcutaneous Formulation of Efgartigimod PH20 SC in Adults With Pemphigus (Vulgaris or Foliaceus)

• Sponsor: argenx (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04598451
• Collaborator: (none)
• Enrollment: 213
• Locations: 124
• Arms: 2
• Anticipated Duration (Months): 35.7
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a prospective, multicenter, randomized, double-blinded, placebo-controlled trial to investigate the efficacy, safety, patient outcome measures, tolerability, immunogenicity, PK, and PD of efgartigimod PH20 SC in adult participants aged from 18 years with PV or PF. The trial comprises a screening period of up to 3 weeks, a treatment period of up to 30 weeks, and an 8-week follow-up period for participants who do not enroll into the open-label extension (OLE) trial ARGX-113-1905. The primary objective of the ARGX-113-1904 trial is to demonstrate the efficacy of subcutaneous administration of efgartigimod co-formulated with recombinant human hyaluronidase PH20 (Efgartigimod PH20 SC) compared to placebo in the treatment of participants with Pemphigus Vulgaris (PV). Secondary objectives are to also demonstrate the efficacy of efgartigimod PH20 SC in the treatment of participants with Pemphigus Foliaceus (PF), and to demonstrate early onset of action and a prednisone-sparing effect. After confirmation of eligibility, participants will be randomized in a 2: 1 ratio to receive efgartigimod PH20 SC or placebo

Condition or Disease	Intervention/Treatment	Phase
Pemphigus Vulgaris; Pemphigus Foliaceus	Biological: efgartigimod PH20 SC; Other: Placebo; Drug: prednisone	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 213 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blinded, Placebo-Controlled Trial to Investigate the Efficacy, Safety, and Tolerability of Efgartigimod PH20 SC in Adult Patients With Pemphigus (Vulgaris or Foliaceus)
• Actual Study Start Date: Dec 1, 2020
• Anticipated Primary Completion Date: Sep 27, 2023
• Anticipated Study Completion Date: Nov 22, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: efgartigimod PH20 SC patients receiving efgartigimod PH20 SC on top of prednisone	Biological: efgartigimod PH20 SC; Subcutaneous injection of efgartigimod using rHuPH20 (PH20) as a permeation enhancer; Drug: prednisone; Oral prednisone tablets
Experimental: placebo patients receiving placebo on top of prednisone	Other: Placebo; Subcutaneous injection of placebo; Drug: prednisone; Oral prednisone tablets

Outcome Measures

Primary Outcome Measures

1. Proportion of Pemphigus Vulgaris (PV) participants who achieve complete clinical remission (CR) on minimal Prednisone therapy [30 weeks treatment period]

   Proportion of Pemphigus Vulgaris participants who achieve Clinical Remission on minimal Prednisone therapy

Secondary Outcome Measures

1. Proportion of Pemphigus Vulgaris (PV) and Pemphigus Foliaceus (PF) participants who achieve complete clinical remission (CR) on minimal Prednisone therapy [30 weeks treatment period]

   Proportion of Pemphigus Vulgaris and Pemphigus Foliaceus participants who achieve complete clinical remission on minimal Prednisone therapy

2. Cumulative prednisone dose over the trial in Pemphigus Vulgaris participants [Up to 30 weeks]

   Cumulative prednisone dose over the trial in Pemphigus Vulgaris participants

3. Time to complete clinical remission in Pemphigus Vulgaris participants [Up to 30 weeks]

   Time to complete clinical remission in Pemphigus Vulgaris participants

4. Time to Disease Control (DC) in Pemphigus Vulgaris (PV) participants [Up to 30 weeks]

   Time to Disease Control in Pemphigus Vulgaris participants

5. Proportion of Pemphigus Foliaceus (PF) participants who achieve complete clinical remission (CR) on minimal prednisone therapy [30 weeks treatment period]

   Proportion of Pemphigus Foliaceus (PF) participants who achieve complete clinical remission (CR) on minimal prednisone therapy

6. Cumulative prednisone dose over the trial in Pemphigus Vulgaris and Pemphigus Foliaceus participants [Up to 30 weeks]

   Cumulative prednisone dose over the trial in Pemphigus Vulgaris and Pemphigus Foliaceus participants

7. Time to complete clinical remission in Pemphigus Vulgaris and Pemphigus Foliaceus participants [Up to 30 weeks]

   Time to complete clinical remission in Pemphigus Vulgaris and Pemphigus Foliaceus participants

8. Time to disease control in Pemphigus Vulgaris and Pemphigus Foliaceus participants [Up to 30 weeks]

   Time to disease control in Pemphigus Vulgaris and Pemphigus Foliaceus participants

9. Rate of treatment failure [Up to 30 weeks]

   Rate of treatment failure

10. Rate of flare [Up to 30 weeks]

    Rate of flare

11. Pemphigus Disease Area Index at each visit [Up to 41 weeks]

    Pemphigus Disease Area Index at each visit

12. Incidence of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE) [Up to 41 weeks]

    Incidence of Treatment-Emergent Adverse Events, Adverse Events of Special Interest, and Serious Adverse Events

13. Severity of Treatment-Emergent Adverse Events (TEAE), Adverse Events of Special Interest (AESI), and Serious Adverse Events (SAE) [Up to 41 weeks]

    Severity of Treatment-Emergent Adverse Events, Adverse Events of Special Interest, and Serious Adverse Events

14. Composite Glucocorticoid Toxicity Index (C-GTI) comprising the Aggregate Improvement Score (AIS) and the Cumulative Worsening Score (CWS) [Up to 30 weeks]

    Composite Glucocorticoid Toxicity Index comprising the Aggregate Improvement Score and the Cumulative Worsening Score

15. EuroQol Five-Dimension Five-Level Scale (EQ-5D-5L) score [30 weeks treatment period]

    EuroQol Five-Dimension Five-Level Scale score

16. Autoimmune Bullous Disease Quality of Life (ABQOL) score [30 weeks treatment period]

    Autoimmune Bullous Disease Quality of Life score

17. Efgartigimod serum concentrations [Up to 38 weeks]

    Efgartigimod serum concentrations

18. Total immunoglobulin G and subtype (IgG1, IgG2, IgG3, IgG4) serum levels [Up to 41 weeks]

    Total immunoglobulin G and subtype (IgG1, IgG2, IgG3, IgG4) serum levels

19. Anti desmoglein-1 and -3 autoantibodies serum levels [Up to 41 weeks]

    Anti desmoglein-1 and -3 autoantibodies serum levels

20. Incidence of anti-drug antibodies (ADA) to efgartigimod PH20 SC [Up to 38 weeks]

    Incidence of anti-drug antibodies to efgartigimod PH20 SC

21. Prevalence of anti-drug antibodies (ADA) to efgartigimod PH20 SC [Up to 38 weeks]

    Prevalence of anti-drug antibodies to efgartigimod PH20 SC

22. Incidence of antibodies produced against recombinant human hyaluronidase (rHuPH20) (plasma levels) [Up to 31 weeks]

    Incidence of antibodies produced against recombinant human hyaluronidase (rHuPH20) (plasma levels)

23. Prevalence of antibodies produced against recombinant human hyaluronidase (rHuPH20) [Up to 31 weeks]

    Prevalence of antibodies produced against recombinant human hyaluronidase (rHuPH20)

24. Number of participants or caregivers completing the self-administration training [Up to 41 weeks]

    Number of participants or caregivers completing the self-administration training

25. Percentage of participants or caregivers completing the self-administration training [Up to 41 weeks]

    Percentage of participants or caregivers completing the self-administration training

26. Number of participants or caregivers determined by the site staff to be sufficiently competent to self-administer efgartigimod PH20 SC [Up to 41 weeks]

    Number of participants or caregivers determined by the site staff to be sufficiently competent to self-administer efgartigimod PH20 SC

27. Percentage of participants or caregivers determined by the site staff to be sufficiently competent to self-administer efgartigimod PH20 SC [Up to 41 weeks]

    Percentage of participants or caregivers determined by the site staff to be sufficiently competent to self-administer efgartigimod PH20 SC

28. Number of participants or caregivers that self-administer efgartigimod PH20 SC under site staff supervision [Up to 41 weeks]

    Number of participants or caregivers that self-administer efgartigimod PH20 SC under site staff supervision

29. Percentage of participants or caregivers that self-administer efgartigimod PH20 SC under site staff supervision [Up to 41 weeks]

    Percentage of participants or caregivers that self-administer efgartigimod PH20 SC under site staff supervision

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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 is male or female, and aged from 18 years at the time of signing the informed consent form (ICF).

3. The participant has a clinical diagnosis of PV (mucosal, cutaneous, mucocutaneous) or PF which has been confirmed by cutaneous histology, positive direct immunofluorescence (IF), and positive indirect IF and/or enzyme-linked immunosorbent assay (ELISA).

4. The participant meets one of the following profiles:

5. Newly diagnosed disease with PDAI ≥15 at baseline and naïve to treatment

6. Newly diagnosed disease with PDAI ≥15 while receiving a first course of oral prednisone (or equivalent). According to clinical judgment, the participant has shown no significant improvement of PV or PF signs for at least 2 weeks before baseline and is considered fit to start prednisone treatment at 0.5 mg/kg qd at baseline.

7. Experiencing flare with PDAI ≥15, a maximum of 4 years since diagnosis, and off prednisone therapy ± a conventional immunosuppressant (e.g., azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil) or dapsone. Note: conventional immunosuppressants and dapsone must be discontinued before baseline.

8. Experiencing flare with PDAI ≥15, a maximum of 4 years since diagnosis, and receiving a tapered dose of oral prednisone (or the equivalent), provided that prednisone has been given at stable dose ± a conventional immunosuppressant for at least 2 weeks and patients are fit to start prednisone treatment at 0.5 mg/kg qd at baseline.

9. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating clinical trials and:

10. Male participants: Male participants must agree to use acceptable method of contraception, and not donate sperm from signing the ICF until the end of the study.

11. Female participants: Women of childbearing potential must:

• have a negative serum pregnancy test at screening and negative urine pregnancy test at baseline before the IMP can be administered.

• agree to use a highly effective or acceptable contraception method, which should be maintained at minimum until after the last dose of IMP

1. For Japanese participants enrolled in sites in Japan only: A Japanese participant is defined as a participant whose parents and 4 grandparents are Japanese, and who has Japanese nationality, was born in Japan, has not lived outside of Japan for a total of

10 years, and currently lives in Japan.

Exclusion Criteria:

1. Participant has a confirmed diagnosis of paraneoplastic pemphigus, drug-induced pemphigus, pemphigus vegetans, pemphigus erythematosus, or any other non-PV/non-PF autoimmune blistering disease.

2. Participants with mild disease severity as defined by PDAI <15 at baseline.

3. Participants who show a significant improvement of PV or PF in the period from screening to baseline according to clinical judgment (eg, the patient has achieved DC or a substantial reduction in PDAI activity score during screening period).

4. The participant has been administered therapy(ies) other than oral prednisone or conventional immunosuppressants (e.g., azathioprine, cyclophosphamide, methotrexate, mycophenolate mofetil) or dapsone within 2 months before the baseline visit and that can affect clinical disease activity. For example, excluded medications are intravenous methylprednisolone, dapsone, sulfasalazine, tetracyclines, nicotinamide at doses above the recommended daily allowance (RDA)/dietary reference intake (DRI), plasmapheresis/ plasma exchange, immunoadsorption, and IVIg.

5. Use of any monoclonal antibody (including rituximab or another anti-CD20 biologic) within 6 months before the baseline visit.

6. Known hypersensitivity to any of the components of the administered treatments.

7. The participant has a known contraindication to oral prednisone.

8. The participant has a history of refractory disease, as defined by a failure to respond to first-line and second-line therapies

9. Participants who have a history of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥3 years before first IMP administration. Participants with any of the following cancers can be included at any time, provided they are adequately treated prior to their participation in the study:

• Basal cell or squamous cell skin cancer,

• Carcinoma in situ of the cervix,

• Carcinoma in situ of the breast,

• Incidental histological finding of prostate cancer

1. 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 patient at undue risk.

2. Pregnant and lactating women and those intending to become pregnant during the trial.

3. Current or history (i.e. within 12 months of screening) of alcohol, drug, or medication abuse.

4. Any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of clinical symptoms of PV or PF or put the participant at undue risk.

5. The participant has a Karnofsky Performance score <60%.

6. Vaccination with live viral vaccines within 28 days prior to randomization.

7. The participant has clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection.

8. Positive serum test at screening for an active viral infection with any of the following conditions: Hepatitis B Virus, Hepatitis C Virus , HIV.

9. The participant has total immunoglobulin G (IgG) <6 g/L at screening.

10. The participant has previously participated in a trial with efgartigimod and has received at least one administration of IMP.

11. Use of an investigational drug within 3 months or 5 half-lives of the drug (whichever is longer) prior to first IMP administration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigator site 77 - US0010086	Birmingham	Alabama	United States	35233
2	Investigator site 97 - US0010091	Scottsdale	Arizona	United States	85259
3	Investigator site 121 - US0010092	Redwood City	California	United States	94063
4	Investigator site 44 - US0010101	Aurora	Colorado	United States	80045
5	Investigator site 2 - US0010087	Boca Raton	Florida	United States	33428
6	Investigator site 9 - US0010099	Florida City	Florida	United States	33756
7	Investigator site 99 - US0010117	Miami	Florida	United States	33173
8	Investigator site 78 - US0010109	Orlando	Florida	United States	32827
9	Investigator site 61 - US0010090	Minneapolis	Minnesota	United States	55455
10	Investigator site 102 - US0010098	Saint Louis	Missouri	United States	63110
11	Investigator site 19 - US0010088	Buffalo	New York	United States	14203-1070
12	Investigator site 60 - US0010096	Durham	North Carolina	United States	27710
13	Investigator site 20 - US0010094	Cleveland	Ohio	United States	44106-1716
14	Investigator site 73 - US00100	Philadelphia	Pennsylvania	United States	19104
15	Investigator site 101 - US0010097	Philadelphia	Pennsylvania	United States	19140
16	Investigator site 98 - US0010107	Dallas	Texas	United States	75246
17	Investigator site 1 - US0010084	Dripping Springs	Texas	United States	78620
18	Investigator site 88 - US0010114	Houston	Texas	United States	77008
19	Investigator site 59 - US0010106	Norfolk	Virginia	United States	23502
20	Investigator site 24 - AU0610006	Sydney	New South Wales	Australia	2217
21	Investigator site 5 - AU0610007	Parkville	Victoria	Australia	3050
22	Investigator site 103 - AU0610013	Melbourne		Australia	3065
23	Investigator site 30 - BG350012	Pleven		Bulgaria	5800
24	Investigator site 31 - BG3590013	Plovdiv		Bulgaria	4000
25	Investigator site 4 - BG3590010	Sofia		Bulgaria	1431
26	Investigator site 2 - BG3590009	Sofia		Bulgaria	1510
27	Investigator site 13 - BG3590011	Sofia		Bulgaria	1606
28	Investigator site 110 - CN0860017	Beijing		China	100034
29	Investigator site 111 - CN0860018	Chendu		China	610000
30	Investigator site 118 - CN0860023	Fujian		China	350005
31	Investigator site 120 - CN0860022	Guangzhou		China	510000
32	Investigator site 109 - CN0860021	Guanzhou		China	510000
33	Investigator site 119 - CN0860024	Nanjing		China
34	Investigator site 112 - CN0860020	Shanghai		China	200025
35	Investigator site 108 - CN0860016	Shanghai		China	200040
36	Investigator site 113 - CN0860025	Wuhan		China	430022
37	Investigator site 123 - CN0860019	Wuhan		China	430022
38	Investigator site 34 - FR0330028	Bobigny		France	93000
39	Investigator site 33 - FR0330027	La Tronche		France	38700
40	Investigator site 46 - FR0330029	Rouen		France	76031
41	Investigator site 32 - FR0330026	Saint-Étienne		France	42055
42	Investigator site 63 - GE9950014	Tbilisi		Georgia	0159
43	Investigator site 35 - GE9950013	Tbilisi		Georgia	0162
44	Investigator site 36 - GE9950015	Tbilisi		Georgia	0179
45	Investigator site 64 - DE0490029	Berlin		Germany	10117
46	Investigator site 48 - DE0490030	Dresden		Germany	01307
47	Investigator site 49 - DE0490024	Frankfurt am main		Germany	60590
48	Investigator site 47 - DE0490023	Freiburg		Germany	79104
49	Investigator site 38 - DE0490028	Kiel		Germany	24105
50	Investigator site 37 - DE0490002	Lübeck		Germany	23538
51	Investigator site 68 - DE0490001	Marburg		Germany	35043
52	Investigator site 25 - DE0490025	Tübingen		Germany	72076
53	Investigator site 79 - DE0490027	Ulm		Germany	89081
54	Investigator site 21 - DE0490026	Würzburg		Germany	97080
55	Investigator site 40 - GR0300004	Athens		Greece	11525
56	Investigator site 51 - GR0300006	Athens		Greece	16121
57	Investigator site 69 - GR0300001	Athens		Greece	16121
58	Investigator site 39 - GR0300003	Chaïdári		Greece	12462
59	Investigator site 50 - GR0300002	Thessaloníki		Greece	54643
60	Investigator site 41 - GR0300005	Thessaloníki		Greece	56429
61	Investigator site 22 - HU0360003	Debrecen		Hungary	4032
62	Investigator site 14 - HU0360001	Pécs		Hungary	7632
63	Investigator site 42 - HU0360002	Szeged		Hungary	6720
64	Investigator site 80 - IN0910002	Ahmedabad		India	380016
65	Investigator site 100 - IN0910001	Chandigarh		India	160012
66	Investigator site 90 - IN0910004	Lucknow		India	226005
67	Investigator site 91 - IN0910003	Nagpur		India	440003
68	Investigator site 12 - ISR9720002	Tel Aviv		Israel	64239
69	Investigator site 11 - IT0390006	Roma	Lazio	Italy	00167
70	Investigator site 104 - IT0390039	Catania		Italy	95123
71	Investigator site 52 - IT0390031	Firenze		Italy	50125
72	Investigator site 92 - IT0390030	Genova		Italy	16132
73	Investigator site 70 - IT0390038	Perugia		Italy	06129
74	Investigator site 43 - IT390005	Roma		Italy	00168
75	Investigator site 71 - IT0390040	Siena		Italy	53100
76	Investigator site 94 - JP0810046	Aichi		Japan	480-1195
77	Investigator site 81 - JP0810040	Hiroshima		Japan	734-8551
78	Investigator site 85 - JP0810050	Kurume		Japan	830-001
79	Investigator site 82 - JP0810042	Kōfu		Japan	400-8506
80	Investigator site 84 - JP0810047	Okayama		Japan	700-8558
81	Investigator site 93 - JP0810041	Okayama		Japan	701-0192
82	Investigator site 86 - JP0810049	Osaka		Japan	545-8586
83	Investigator site 74 - JP0810045	Sapporo		Japan	060-8648
84	Investigator site 124 - JP0810067	Sendai		Japan	980-8574
85	Investigator site 83 - JP0810043	Tokyo		Japan	113-8431
86	Investigator site 26 - PL0480027	Katowice		Poland	40-081
87	Investigator site 95 - PL0480036	Poznań		Poland	60-369
88	Investigator site 27 - PL0480025	Rzeszów		Poland	35-055
89	Investigator site 28 - PL0480028	Wrocław		Poland	50-566
90	Investigator site 72 - PL0480032	Łódź		Poland	90-647
91	Investigator site 106 - RO0400013	Bucharest		Romania	011216
92	Investigator site 105 - RO0400014	Cluj-Napoca		Romania	400006
93	Investigator site 107 - RO0400015	Iaşi		Romania	700111
94	Investigator site 54 - RU0070035	Chelyabinsk		Russian Federation	454092
95	Investigator site 58 - RU0070033	Ekaterinburg		Russian Federation	620076
96	Investigator site 57 - RU0070029	Kazan		Russian Federation	420111
97	Investigator site 55 - RU0070030	Krasnodar		Russian Federation	350020
98	Investigator site 53 - RU0070032	Rostov-on-Don		Russian Federation	344002
99	Investigator site 56 - RU0070031	Saint Petersburg		Russian Federation	191123
100	Investigator site 65 - RU0070034	Saint Petersburg		Russian Federation	197022
101	Investigator site 66 - RU0070028	Saratov		Russian Federation	410012/410028
102	Investigator site 122 - RS3810010	Belgrade		Serbia	11000
103	Investigator site 116 - RS3810011	Belgrad		Serbia	11000
104	Investigator site 115 - RS3810012	Niš		Serbia	18000
105	Investigator site 114 - RS3810009	Novi Sad		Serbia	21000
106	Investigator site 29 - ES0340026	Barcelona		Spain	08907
107	Investigator site 15 - ES0340032	Barcelona		Spain	8036
108	Investigator site 67 - ES0340034	Madrid		Spain	28007
109	Investigator site 10 - ES0340025	Madrid		Spain	28034
110	Invetistigator site 8 - ES0340029	Madrid		Spain	28041
111	Investigator site 6 - ES0340027	Madrid		Spain	28046
112	Investigator site 23 - ES0340031	Pamplona		Spain	31008
113	Investigator site 7 - ES0340028	Sevilla		Spain	41013
114	Investigator site 76 - TR0900020	Gaziantep		Turkey	27310
115	Investigator site 75 - TR0900012	Istanbul		Turkey	34098
116	Investigator site 87 - TR0900011	Istanbul		Turkey	34722
117	Investigator site 89 - UA3800017	Dnipro		Ukraine	49074
118	Investigator site 45 - UA3800023	Ivano-Frankivs'k		Ukraine	76018
119	Investigator site 16 - UA3800020	Kyiv		Ukraine	4050
120	Investigator site 18 - UA3800019	Kyiv		Ukraine	4209
121	Investigator site 62 - UA3800021	Lviv		Ukraine	79013
122	Investigator site 17 - UA3800018	Zaporizhzhia		Ukraine	69063
123	Investigator site 117 - UK0440021	Birmingham		United Kingdom	B15 2GW
124	Investigator site 96 - UK0440022	Bristol		United Kingdom	BS2 8HW

Sponsors and Collaborators

• argenx

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: argenx
• ClinicalTrials.gov Identifier: NCT04598451
• Other Study ID Numbers: ARGX-113-1904
• First Posted: Oct 22, 2020
• Last Update Posted: Aug 1, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Pemphigus; Prednisone

Study Results

No Results Posted as of Aug 1, 2022