A Study to Assess the Safety and Efficacy of a Subcutaneous Formulation of Efgartigimod in Adults With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP, an Autoimmune Disorder That Affects the Peripheral Nerves)

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Clinical Trial

— ADHERE  

Official title:

A Phase 2 Trial to Investigate the Efficacy, Safety, and Tolerability of Efgartigimod PH20 SC in Adult Patients With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04281472
• Other study ID #: ARGX-113-1802
• Secondary ID: 2019-003076-39
• Status: Completed
• Phase: Phase 2
• Start date: April 15, 2020
• Est. completion date: May 11, 2023

Study information

• Verified date: August 2023
• Source: argenx
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 2 study to evaluate the safety and efficacy of the subcutaneous formulation of efgartigimod in adults with CIDP.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 322
• Est. completion date: May 11, 2023
• Est. primary completion date: May 11, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Ability to understand the requirements of the trial, provide written informed consent (include 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. Male or female patient aged 18 years or older, at the time of signing the informed consent.

3. Diagnosed with probable or definite CIDP according to criteria of the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS 2010), progressing or relapsing forms.

4. CIDP Disease Activity Status (CDAS) score =2 at screening.

5. INCAT score =2 at the first run-in visit (for patients entering run-in) or stage A baseline (for treatment-naïve patients with documented evidence for worsening on the total adjusted INCAT disability score within 3 months prior to screening). Patients with an INCAT score of 2 at trial entry must have this score exclusively from the leg disability score; for patients with an INCAT score of =3 at trial entry, there are no specific requirements for arm or leg scores.

6. Fulfilling any of the following treatment conditions:

• Currently treated with pulsed corticosteroids, oral corticosteroids equivalent to prednisolone/prednisone =10mg/day, and/or IVIg or SCIg, if this treatment has been started within the last 5 years before screening, and the patient is willing to discontinue this treatment at the first run-in visit; or

• Without previous treatment (treatment-naive); or

• Treatment with corticosteroids and/or IVIg or SCIg discontinued at least 6 months prior to screening Note: Patients not treated with monthly or daily corticosteroids, IVIg or SCIg for at least 6 months prior to screening are considered as equal to treatment-naïve patients.

7. Women of childbearing potential who have a negative pregnancy test at screening and a negative urine pregnancy test up to Stage A baseline.

8. Women of childbearing potential must use an acceptable method of contraception from signing the ICF until the date of the last dose of IMP

Exclusion Criteria:

1. Pure sensory atypical CIDP (EFNS/PNS definition).

2. Polyneuropathy of other causes, including the following: Multifocal motor neuropathy; Monoclonal gammopathy of uncertain significance with anti-myelin associated, glycoprotein immunoglobulin M (IgM) antibodies; Hereditary demyelinating neuropathy; Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin change syndromes; Lumbosacral radiculoplexus neuropathy; Polyneuropathy most likely due to diabetes mellitus; Polyneuropathy most likely due to systemic illnesses; Drug- or toxin-induced polyneuropathy.

3. Any other disease that could better explain the patient's signs and symptoms.

4. Any history of myelopathy or evidence of central demyelination.

5. Current or past history (within 12 months of screening) of alcohol, drug or medication abuse.

6. Severe psychiatric disorder (such as severe depression, psychosis, bipolar disorder), history of suicide attempt, or current suicidal ideation that in the opinion of the investigator could create undue risk to the patient or could affect adherence with the trial protocol.

7. Patients with clinically significant active or chronic uncontrolled bacterial, viral, or fungal infection at screening, including patients who test positive for an active viral infection at screening with: Active Hepatitis B Virus (HBV): serologic panel test results indicative of an active (acute or chronic) infection; Active Hepatitis C Virus (HCV): serology positive for HCV-Ab; Human Immunodeficiency Virus (HIV) positive serology associated with an Acquired Immune Deficiency Syndrome (AIDS)-defining condition or with a cluster of differentiation 4 (CD4) count =200 cells/mm3.

8. Total IgG level <6 g/L at screening.

9. Treatment with the following: Within 3 months (or 5 half-lives of the drug, whichever is longer) before screening: plasma exchange or immunoadsorption, any concomitant Fc-containing therapeutic agents or other biological, or any other investigational product; Within 6 months before screening: rituximab, alemtuzumab, any other monoclonal antibody, cyclophosphamide, interferon, tumor necrosis factor-alpha inhibitors, fingolimod, methotrexate, azathioprine, mycophenolate, any other immunomodulating or immunosuppressive medications, and oral daily corticosteroids >10 mg/day. Note: Patients using IVIg, SCIg, pulsed corticosteroids, and oral daily corticosteroids =10 mg/day can be included.

Patients who (intend to) use prohibited medications and therapies (see protocol) during the trial.

10. Pregnant and lactating women and those intending to become pregnant during the trial or within 90 days after last IMP administration.

11. Patients with any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of clinical symptoms of CIDP.

12. Patients who received a live-attenuated vaccine fewer than 28 days before screening. Receiving an inactivated, sub-unit, polysaccharide, or conjugate vaccine any time before screening is not exclusionary.

13. Patients who have a history of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for =3 years before the first IMP administration. Patients with the following cancer can be included anytime: Adequately treated basal cell or squamous cell skin cancer, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, or Incidental histological finding of Prostate cancer (TNM [tumor, nodes, and metastases classification] stage T1a or T1b).

14. Patients who previously participated in a trial with efgartigimod and have received at least one administration of IMP.

15. Patients with known medical history of hypersensitivity to any of the ingredients of IMP.

16. Patients with clinical evidence of other significant serious disease or patients who underwent a recent or have a planned major surgery, or any other reason which could confound the results of the trial or put the patient at undue risk.

Related Conditions & MeSH terms

• Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
• Polyneuropathies
• Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Intervention

Biological:
• efgartigimod PH20 SC in stage B
Stage A: efgartigimod PH20 SC, Stage B: efgartigimod PH20 SC

Other:
• placebo in stage B
Stage A: N/A, stage B: placebo

Locations

Country	Name	City	State
Austria	Investigator site 0430009	Graz
Austria	Investigator site 0430007	Innsbruck
Austria	Investigator site 0430008	Linz
Austria	Investigator site 0430006	Salzburg
Austria	Investigator site 0430005	Wien
Belgium	Investigator site 0320017	Brussel
Belgium	Investigator site 0320019	Brussel
Belgium	Investigator site 0320016	Edegem
Belgium	Investigator site 0320009	Leuven
Belgium	Investigator site 0320024	Liège
Belgium	Investigator site 0320022	Woluwe-Saint-Lambert
Bulgaria	Investigator site 3590007	Pleven
Bulgaria	Investigator site 3590005	Sofia
Bulgaria	Investigator site 3590008	Sofia
Bulgaria	Investigator site 3590009	Sofia
China	Investigator site 0860033	Beijing
China	Investigator site 0860030	Changchun
China	Investigator site 0860041	Changsha
China	Investigator site 0860036	Chengdu
China	Investigator site 0860049	Chifeng
China	Investigator site 0860038	Fuzhou
China	Investigator site 0860032	Guanzhou
China	Investigator site 0860050	Guanzhou
China	Investigator site 0860045	Guiyang
China	Investigator site 0860046	Hangzhou
China	Investigator site 0860035	Hanzhou
China	Investigator site 0860031	Jinan
China	Investigator site 0860063	Jining
China	Investigator Site 0860040	Nanchang
China	Investigator site 0860044	Nanchang
China	Investigator site 0860051	Nanchang
China	Investigator site 0860043	Nanjing
China	Investigator site 0860043	Nanjing
China	Investigator site 0860028	Shangai
China	Investigator site 0860047	Shanghai
China	Investigator site 0860052	Shanghai
China	Investigator site 0860042	Taiyuan
China	Investigator site 0860029	Wuhan
China	Investigator site 0860034	Wuhan
China	Investigator site 0860037	Xi'an
China	Investigator site 0860048	Xi'an
China	Investigator site 0860054	Xiangyang
Czechia	Investigator site 4200010	Hradec Králové
Denmark	Investigator site 0450002	Aarhus
Denmark	Investigator site 0450001	Copenhagen
Denmark	Investigator site 0450003	Odense
France	Investigator site 0330034	Angers
France	Investigator site 0330013	Bordeaux
France	Investigator site 0330033	Clermont-Ferrand
France	Investigator site 0330025	Garches
France	Investigator site 0330023	Le Kremlin-Bicêtre
France	Investigator site 0330024	Limoges
France	Investigator site 0330022	Nantes
France	Investigator site 0330021	Nice
France	Investigator site 0330035	Paris
France	Investigator site 0330020	Strasbourg
Georgia	Investigator site 9950020	Kutaisi
Georgia	Investigator Site 9950002	Tbilisi
Georgia	Investigator Site 9950003	Tbilisi
Georgia	Investigator Site 9950004	Tbilisi
Georgia	Investigator site 9950005	Tbilisi
Germany	Investigator site 0490017	Berlin
Germany	Investigator site 0490018	Berlin
Germany	Investigator site 0490044	Bochum
Germany	Investigator site 0490045	Essen
Germany	Investigator site 0490021	Göttingen
Germany	Investigator site 0490014	Hannover
Germany	Investigator site 0490016	Kiel
Germany	Investigator site 0490013	Köln
Germany	Investigator site 0490020	Leipzig
Germany	Investigator site 0490019	Potsdam
Germany	Investigator site 0490015	Regensburg
Hungary	Investigator site 0360017	Budapest
Hungary	Investigator site 0360018	Kistarcsa
Israel	Investigator site 9720006	H_olon
Israel	Investigator site 9720005	Ramat Gan
Israel	Investigator site 9720004	Tel Aviv
Italy	Investigator site 0390022	Brescia
Italy	Investigator site 0390029	Firenze
Italy	Investigator site 0390024	Genova
Italy	Investigator site 0390027	Messina
Italy	Investigator site 0390003	Milano
Italy	Investigator site 0390026	Milano
Italy	Investigator site 0390007	Napoli
Italy	Investigator site 0390023	Pisa
Italy	Investigator site 0390008	Roma
Italy	Investigator site 0390028	Siena
Italy	Investigator site 0390042	Torino
Japan	Investigator site 0810035	Bunkyo-Ku
Japan	Investigator site 0810002	Chiba
Japan	Investigator site 0810034	Chuo Ku
Japan	Investigator site 0810030	Fuchu
Japan	Investigator site 0810031	Fukuoka
Japan	Investigator site 0810065	Ginowan
Japan	Investigator site 0810066	Hakodate
Japan	Investigator site 0810058	Hiroshima
Japan	Investigator site 0810036	Itabashi
Japan	Investigator site 0810029	Kawaguchi
Japan	Investigator site 0810062	Kawasaki
Japan	Investigator site 0810026	Kodaira
Japan	Investigator site 0810061	Kyoto
Japan	Investigator site 0810027	Mibu
Japan	Investigator site 0810032	Nagoya
Japan	Investigator site 0810003	Osaka
Japan	Investigator site 0810007	Osaka
Japan	Investigator site 0810028	Sagamihara
Japan	Investigator site 0810033	Sapporo
Japan	Investigator site 0810037	Shinjuku-Ku
Japan	Investigator site 0810063	Suita
Japan	Investigator site 0810064	Tokushima
Japan	Investigator site 0810060	Yokohama
Latvia	Investigator site 3710001	Riga
Netherlands	Investigator site 0310010	Amsterdam
Netherlands	Investigator site 0310011	Rotterdam
Poland	Investigator site 0480019	Bialystok
Poland	Investigator site 0480023	Katowice
Poland	Investigator site 0480017	Kraków
Poland	Investigator site 0480024	Kraków
Poland	Investigator site 0480020	Lódz
Poland	Investigator site 0480018	Lublin
Poland	Investigator site 0480022	Warsaw
Romania	Investigation site 0400002	Brasov
Romania	Investigator site 0400001	Bucharest
Romania	Investigator site 0400004	Constanta
Romania	Investigator site 0400003	Timisoara
Russian Federation	Investigator site 0070017	Kazan
Russian Federation	Investigator site 0070023	Kazan
Russian Federation	Investigator site 0070016	Moscow
Russian Federation	Investigator site 0070020	Moscow
Russian Federation	Investigator site 0070018	Perm
Russian Federation	Investigator site 0070019	Rostov-on-Don
Russian Federation	Investigator site 0070014	Saint Petersburg
Russian Federation	Investigator site 0070021	Saransk
Serbia	Investigator site 3810001	Belgrad
Serbia	Investigator site 3810003	Belgrad
Serbia	Investigator site 3810004	Kragujevac
Spain	Investigator site 0340020	Alicante
Spain	Investigator site 0340021	Badalona
Spain	Investigator site 0340038	Barcelona
Spain	Investigator site 0340019	Córdoba
Spain	Investigator site 0340017	Madrid
Spain	Investigator site 0340018	Madrid
Spain	Investigator site 0340016	Sevilla
Taiwan	Investigator site 8860014	Kaohsiung
Taiwan	Investigator site 8860015	Taichung
Taiwan	Investigator site 8860013	Tainan
Taiwan	Investigator site 8860011	Taipei
Taiwan	Investigator site 8860012	Taipei
Taiwan	Investigator site 8860016	Taipei
Taiwan	Investigator site 8860017	Taoyuan
Turkey	Investigator site 0900025	Bursa
Turkey	Investigator site 0900023	Istanbul
Turkey	Investigator site 0900021	Izmir
Turkey	Investigator site 0900022	Samsun
Turkey	Investigator site 0900024	Sariçam
Ukraine	Investigator site 3800012	Dnipro
Ukraine	Investigator site 3800014	Dnipropetrovs'k
Ukraine	Investigator site 3800010	Ivano-Frankivs'k
Ukraine	Investigator site 3800015	Kharkiv
Ukraine	Investigator site 3800013	Kyiv
Ukraine	Investigator site 380008	Luts'k
Ukraine	Investigator site 3800015	Vinnytsia
Ukraine	Investigator site 380009	Vinnytsia
Ukraine	Investigator site 3800011	Zaporizhzhya
United Kingdom	Investigator site 0440017	Glasgow
United Kingdom	Investigator site 0440015	Inverness
United Kingdom	Investigator site 0440026	London
United Kingdom	Investigator site 0440016	Oxford
United Kingdom	Investigator site 0440018	Sheffield
United Kingdom	Investigator site 0440019	Stoke-on-Trent
United Kingdom	Investigator site 0440028	Tooting
United States	Investigator site 0010125	Augusta	Georgia
United States	Investigator site 0010066	Austin	Texas
United States	Investigator site 0010065	Birmingham	Alabama
United States	Investigator site 0010072	Boca Raton	Florida
United States	Investigator site 0010076	Burlington	Vermont
United States	Investigator Site 0010032	Carlsbad	California
United States	Investigator site 0010057	Centennial	Colorado
United States	Investigator site 0010003	Chapel Hill	North Carolina
United States	Investigator site 0010007	Charlottesville	Virginia
United States	Investigator site 0010051	Cincinnati	Ohio
United States	Investigator site 0010028	Columbia	Missouri
United States	Investigator site 0010064	Columbus	Ohio
United States	Investigator site 0010144	Coral Springs	Florida
United States	Investigator site 0010014	Detroit	Michigan
United States	Investigator site 0010077	Durham	North Carolina
United States	Investigator site 0010063	East Lansing	Michigan
United States	Investigator site 0010015	Fairway	Kansas
United States	Investigator site 0010026	Houston	Texas
United States	Investigator site 0010011	Iowa City	Iowa
United States	Investigator site 0010023	Jacksonville	Florida
United States	Investigator site 0010147	Lexington	Kentucky
United States	Investigator Site 0010068	Maitland	Florida
United States	Investigator site 0010059	Miami	Florida
United States	Investigator site 0010052	Minneapolis	Minnesota
United States	Investigator site 0010070	New Brunswick	New Jersey
United States	Investigator site 0010026	New Haven	Connecticut
United States	Investigator site 0010069	New York	New York
United States	Investigator site 0010074	New York	New York
United States	Investigator site 0010168	New York	New York
United States	Investigator site 0010191	New York	New York
United States	Investigator site 0010004	Orange	California
United States	Investigator site 0010050	Orlando	Florida
United States	Investigator site 0010172	Ormond Beach	Florida
United States	Investigator site 0010075	Patchogue	New York
United States	Investigator site 0010007	Philadelphia	Pennsylvania
United States	Investigator site 0010047	Philadelphia	Pennsylvania
United States	Investigator site 0010013	Phoenix	Arizona
United States	Investigator site 0010067	Pittsburgh	Pennsylvania
United States	Investigator site 0010190	Pomona	California
United States	Investigator site 0010160	Rancho Mirage	California
United States	Investigator site 0010061	Richmond	Virginia
United States	Investigator site 0010009	San Antonio	Texas
United States	Investigator site 0010071	San Francisco	California
United States	Investigator site 0010055	Scottsdale	Arizona
United States	Investigator site 0010006	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
argenx

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Bulgaria,  China,  Czechia,  Denmark,  France,  Georgia,  Germany,  Hungary,  Israel,  Italy,  Japan,  Latvia,  Netherlands,  Poland,  Romania,  Russian Federation,  Serbia,  Spain,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stage A: Percentage of patients with confirmed evidence of clinical improvement(ECI)		Up to 12 weeks during the open-label stage A
Primary	Stage B: Time to first adjusted INCAT deterioration compared to Stage B baseline		Up to 48 weeks during the randomized placebo-controlled stage B
Secondary	Stage A: Time to initial confirmed ECI		Up to 12 weeks during the open-label stage A
Secondary	Stage A: Change from Stage A baseline over time in adjusted INCAT score		Up to 12 weeks during the open-label stage A
Secondary	Stage A: Change from Stage A baseline over time in Medical Research Council (MRC) Sum score		Up to 12 weeks during the open-label stage A
Secondary	Stage A: Change from Stage A baseline over time in I-RODS disability scores		Up to 12 weeks during the open-label stage A
Secondary	Stage A: Change from Stage A baseline over time in TUG score		Up to 12 weeks during the open-label stage A
Secondary	Stage A: Change from Stage A baseline over time in mean grip strength		Up to 12 weeks during the open-label stage A
Secondary	Stage A: Exposure adjusted occurrence of treatment-emergent (serious) adverse events		Up to 12 weeks during the open-label stage A
Secondary	Stage A: Incidence of clinically significant laboratory abnormalities		Up to 12 weeks during the open-label stage A
Secondary	Stage A: Pre-dosing efgartigimod serum concentrations over time		Up to 12 weeks during the open-label stage A
Secondary	Stage A: Changes of serum IgG levels over time		Up to 12 weeks during the open-label stage A
Secondary	Stage A: Percentage of patients with and titers of binding antibodies towards efgartigimod and/or rHuPH20 and the presence of neutralizing antibodies against efgartigimod and/or rHuPH20		Up to 12 weeks during the open-label stage A
Secondary	Stage A: Changes from D1A in EQ-5D-5L over time		Up to 12 weeks during the open-label stage A
Secondary	Stage B: Time to CIDP disease progression	Time to CIDP disease progression is defined by the time from first dose of double-blind IMP to the first I-RODS score decrease =4 points compared to Stage B baseline using the centile metric.	Up to 48 weeks during the randomized placebo-controlled stage B
Secondary	Stage B: Percentage of patients with improved functional level compared to Stage B baseline		Up to 48 weeks during the randomized placebo-controlled stage B
Secondary	Stage B: Change from Stage B baseline over time in adjusted INCAT score		Up to 48 weeks during the randomized placebo-controlled stage B
Secondary	Stage B: Change from Stage B baseline over time in MRC Sum score		Up to 48 weeks during the randomized placebo-controlled stage B
Secondary	Stage B: Change from Stage B baseline over time in 24-item I-RODS disability score		Up to 48 weeks during the randomized placebo-controlled stage B
Secondary	Stage B: Change from Stage B baseline over time in TUG score		Up to 48 weeks during the randomized placebo-controlled stage B
Secondary	Stage B: Change from Stage B baseline over time in mean grip strength		Up to 48 weeks during the randomized placebo-controlled stage B
Secondary	Stage B: Time to 10% decrease in the 24-item I-RODS		Up to 48 weeks during the randomized placebo-controlled stage B
Secondary	Stage B: Exposure adjusted occurrence of treatment-emergent adverse events and serious adverse events		Up to 48 weeks during the randomized placebo-controlled stage B
Secondary	Stage B: Incidence of clinically significant laboratory abnormalities		Up to 48 weeks during the randomized placebo-controlled stage B
Secondary	Stage B: Pre-dosing efgartigimod serum concentrations over time		Up to 48 weeks during the randomized placebo-controlled stage B
Secondary	Stage B: Changes of serum IgG levels over time		Up to 48 weeks during the randomized placebo-controlled stage B
Secondary	Stage B: Percentage of patients with and titers of binding antibodies towards efgartigimod and/or rHuPH20 and the presence of neutralizing antibodies against efgartigimod and/or rHuPH20		Up to 48 weeks during the randomized placebo-controlled stage B
Secondary	Stage B: Changes from D1A in EQ-5D-5L over time		Up to 48 weeks during the randomized placebo-controlled stage B