PemphigusPhase 2NCT04400994
IVIG With Rituximab vs Rituximab as First Line Treatment of Pemphigus
A Phase 2 study testing Rituximab and IVIg in people with Pemphigus, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
Pemphigus is a rare acquired autoimmune disease in which immunoglobulin G (IgG) antibodies target desmosomal proteins to produce intraepithelial, and mucocutaneous blisters. It is potentially fatal and the average mortality of pemphigus vulgaris (PV) was 75% before the introduction of corticosteroids in the early… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pemphigus
- What is being tested?
- Rituximab and IVIg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteHong Kong
- Study dates
- 20 Jun 2020to 30 Jun 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent obtained from patient
- Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
- Newly or recently diagnosed (less than 18 months) diagnosed pemphigus vulgaris or pemphigus foliaceus based on clinical features; histological features of acantholysis via skin or mucosal biopsy; and intercellular staining pattern of indirect immunofluorescence or serological detection of DSG 1 or DSG 3 by enzyme-linked immunosorbent assay (ELISA)
- Moderate to severe active disease, as defined by overall PDAI >= 15 or skin involvement BSA>= 5%. 9 [Annex 1]
- Receiving standard-of-care oral prednisolone up to 1.5 mg/kg/day
- Women who are sexually active and not postmenopausal, agreement to remain abstinent or use 2 effective methods of contraception.
- Ability to comply with study protocol as deemed by investigator's assessment
Who cannot join
- Age <18 or >75
- Pregnant women or nursing mother
- Already diagnosed pemphigus patients diagnosed > 18 months
- Non-consenting patients, or patient who cannot be followed up regularly
- Patient with history of serious allergy or anaphylactic reaction to monoclonal antibody treatment
- Severe heart failure (NYHA Class III or IV)
Show all 27Show fewer
- Unstable angina or myocardiac infarction within last 3 months or post-infarction heart failure
- Anaemia (haemoglobin <10g/dL), Neutropenia (<1000/mm3), Lymphopenia (<900/mm3), thrombocytopenia (<100,000/mm3)
- Renal insufficiency eGFR <60
- Liver insufficiency of ALT/ALT > 2 times normal limit range
- Positive test results for hepatitis C (HCV) serology at screening *Patients who are HepBs Ag positive, or HepBs Ag negative and anti-HepBc Ab - positive: Patients who are HepBs Ag positive - will be started on entecavir 0.5mg daily, and will be referred to a gastroenterologist for further follow up.
- Patients who are HepBs Ag negative, and HBc Ab positive, with detectable HepB DNA levels - will be started on entecavir 0.5mg daily, and will be referred to a gastroenterologist for further follow up.
- Patients who are HepBs Ag negative, HBc Ab positive, with no detectable HepB DNA levels - will be started on entecavir 0.5mg daily, and will be continued on entecavir for at least 18 months after completion of last dose of rituximab.
- Blood test positive for HIV
- Signs of active infection on CXR
- Positive interferon gamma release assay Quantiferon or T.Spot TB test: must be treated with at least 4 weeks post initiation of isoniazid or other TB therapy
- Inherited or acquired severe immunodeficiency
- History of malignancy
- Patient with active severe infection (excluding fungal infections of the nail), which has required antibiotic treatment within 2 week prior to study enrolment
- Infection requiring hospitalisation or intravenous antibiotic treatment within the last 8 weeks prior to enrolment
- Past history of osteomyelitis, or fasciitis, septic arthritis within the last one year
- Patients with drug induced pemphigus. A thorough medication history will be taken to rule out drug induced pemphigus including D-penicillamine, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and cephalosporins
- Evidence of any new or uncontrolled concomitant disease that in the investigators' judgement would preclude the patients participation
- Patients with history of allergy or adverse events to IVIG or rituximab treatment10
- Treatment with intravenous immunoglobulins, plasmaphoresis within the last 8 weeks prior to randomization
- Previous treatment with rituximab or any monoclonal antibody inducing profound lymphopenia
- Treatment with live or attenuated vaccine within the last 28 days prior to randomization
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Use of IVIG in Combination With Rituximab VS Rituximab as the First Line Treatment of Pemphigus
Pemphigus is a rare acquired autoimmune disease in which immunoglobulin G (IgG) antibodies target desmosomal proteins to produce intraepithelial, and mucocutaneous blisters. It is potentially fatal and the average mortality of pemphigus vulgaris (PV) was 75% before the introduction of corticosteroids in the early 1950s.
Traditionally, treatment of pemphigus included high dose systemic corticosteroids with or without adjuvant immunosuppressants. However; the prolonged use of high dose steroids carries significant side effects. A recent randomized trial has proved the efficacy of Rituximab, a monoclonal anti-CD20 antibody against B-lymphocytes, as an efficacious therapy for pemphigus. Early use of rituximab was associated with better clinical outcomes, hence combination treatment of rituximab and intravenous immunoglobulins (IVIG) has shown to be effective for refractory pemphigus cases and can potentially induce long-term complete remission and lower risks infectious complications.
In this study, investigators will evaluate the efficacy and safety of early use of rituximab with or without IVIG in patients with moderate to severe pemphigus using protocols that were similar to those previously published, investigators will also aim to measure the impact of health care economics and in doing so, assess the cost and benefits of both treatment arms.
Read the detailed description
Pemphigus is a rare acquired autoimmune disease in which immunoglobulin G (IgG) antibodies target desmosomal proteins to produce intraepithelial, and mucocutaneous blisters. It is potentially fatal and the average mortality of pemphigus vulgaris (PV) was 75% before the introduction of corticosteroids in the early 1950s.
Traditionally, treatment of pemphigus included high dose systemic corticosteroids with or without adjuvant immunosuppressants. However; the prolonged use of high dose steroids carries significant side effects. A recent randomized trial has proved the efficacy of Rituximab, a monoclonal anti-CD20 antibody against B-lymphocytes, as an efficacious therapy for pemphigus. Furthermore, early use of rituximab was associated with associated with better clinical outcomes. Moreover, combination treatment of rituximab and intravenous immunoglobulins (IVIG) has shown to be effective for refractory pemphigus cases and can potentially induce long-term complete remission and lower risks infectious complications.
Cost effectiveness is an important issue and while combination of IVIG and rituximab has been advocated, the cost of such treatment is substantial and whether it poses any benefit over rituximab alone, or with other more conventional immunosuppressive agents, has not been established. Both treatment approaches have been previously published in high impact journals.
In this study, investigators aim to evaluate the efficacy and safety of early use of rituximab with or without IVIG in patients with moderate to severe pemphigus using protocols that were similar to those previously published. Apart from complete remission and adverse effects, investigators will also aim to measure the impact of health care economics and in doing so, assess the cost and benefits of both treatment arms.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called MabThera
Rituximab would be given intravenously.
- IV Rituximab is prediluted at a dose of 500mg in 500ml of 0.9% normal saline (i.e. 1:1 dilution, 1 mg/ml)
- Initial infusion rate starts at a rate of 50mg/hr (50ml/hr)
- If no hypersensitivity/anaphylaxis reaction occurs, increase infusion rate in 50mg/hr (50 ml/hr) increments every 30 minutes
- Maximum infusion rate is 400 mg/hr (400 ml/hr)
- Subsequent infusion: start at rate of 100mg/hr (100 ml/hr), increase 100mg/hr (100 ml/hr) increments every 30 minutes
- Monitor temperature, BP HR, respiratory rate and SpO2 every 30 minutes
IVIgOther
Also called Privigen
IVIg would be given in combination with Rituximab intravenously. Infusion plan of IVIg:
0 min: 50ml/hour 15 min: 75ml/hour 30 min: 100ml/hour 45 min: 125ml/hour 60 min: 150ml/hour 75 min \& beyond: 180ml/hour
| Study group | Role | What they receive |
|---|---|---|
| Rituximab only | Active comparator | * Rituximab infusion 375mg/m2 body surface area (BSA) weekly for 4 weeks from baseline (week 0, 1, 2, 3)
* Rituximab infusion 375mg/m2 BSA weekly for 4 weeks at week 24 (week 24, 25, 26, 27)
* Rituximab infusion 375mg/m2 BSA weekly for 2 weeks at week 52 (week 52, 53)
* Rituximab infusion 375mg/m2 BSA weekly for 4 weeks at week 76 (week 76, 77)
* A total of 12 doses of rituximab will be given in 55 weeks Receives: Drug: Rituximab |
| Rituximab and IVIG | Experimental | * Rituximab (375 mg/m2 BSA) once a week for 4 weeks (week 1, 2, 3);
* Week 4: Rituximab + IVIG 2g per kg
* Week 5, 6, 7: Above treatment repeated for 2nd cycle, infusion of rituximab (375 mg/m2 BSA) once a week for 4 weeks (week 5, 6, 7);
* Week 8: Rituximab + IVIG 2g/kg
* In months 3, 4, 5, 6, patients received a single infusion of rituximab (375 mg/m2 BSA) plus infusion of 2g/kg IVIG
* Thus in 6-month period patients received a total of 12 infusions of rituximab and 7 infusions of IVIG
* If a patient was clinically free of disease at end of 6 months, additional infusions of IVIG will be given at week 30, 38, 48, 60 and 76
* A total of 12 doses of rituximab and 12 cycles of IVIG will be given Receives: Drug: Rituximab; Other: IVIg |
What is being measured
The primary outcome is the main question the study is designed to answer.
relapse-free complete remission
Percentage of participants who achieve relapse-free complete remission
Measured: From baseline up to 208 weeks
Secondary outcomes (10)
Time to protocol defined disease flare
Time to protocol defined disease flare
Measured: From baseline up to 208 weeks
Duration of complete remission
Duration of complete remission, evaluated by the PDAI activity score
Measured: From baseline up to 208 weeks
Number of protocol defined disease flares
Number of protocol defined disease flares
Measured: From baseline up to 208 weeks
Time to initial complete remission
Time to initial complete remission, evaluated by the PDAI activity score
Measured: From baseline up to 208 weeks
Change in health-related quality of life: Dermatology Life Quality Index (DLQI) Score
Change in health-related quality of life as measured by the Dermatology Life Quality Index (DLQI) Score.
The DLQI is calculated by summing the score of each question resulting in maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.
Measured: Baseline, Week 4, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192
Occurrence of severe treatment adverse events
Safety endpoints: Occurrence of treatment adverse events, serious adverse events (grade 3 or 4) based on common terminology criteria for adverse events (CTCAE). Death from any cause. Adverse events leading to discontinuation, vital signs, and laboratory tests
Measured: Baseline, week 4, 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192
Blood DSG 1 and 3 levels
Blood DSG 1 and 3 levels
Measured: Baseline week 0, week 4, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192
Blood lymphocyte level (CBC)
Blood lymphocyte level (CBC)
Measured: Baseline week 0, week 4, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192
Blood CD19/20 mean B cell counts percentage
Blood CD19/20 mean B cell counts percentage
Measured: Week 0, week 4, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192
Number of rescue therapy given
Number of rescue therapy given
Measured: Baseline up to Week 208
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2020
- Study start20 Jun 2020
- Primary completion31 Dec 2025 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for PemphigusStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Sze-Man Wong, The University of Hong Kong
- Investigators
- Sze Man Wong, MBBS, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04400994
- Sponsor's protocol ID
- UW19-671
- Status last verified
- Jul 2025
- First submitted
- 27 Apr 2020
- Last updated
- 8 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Harman KE, Brown D, Exton LS, Groves RW, Hampton PJ, Mohd Mustapa MF, Setterfield JF, Yesudian PD. British Association of Dermatologists' guidelines for the management of pemphigus vulgaris 2017. Br J Dermatol. 2017 Nov;177(5):1170-1201. doi: 10.1111/bjd.15930. No abstract available.
PubMed 29192996Hertl M, Jedlickova H, Karpati S, Marinovic B, Uzun S, Yayli S, Mimouni D, Borradori L, Feliciani C, Ioannides D, Joly P, Kowalewski C, Zambruno G, Zillikens D, Jonkman MF. Pemphigus. S2 Guideline for diagnosis and treatment--guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV). J Eur Acad Dermatol Venereol. 2015 Mar;29(3):405-14. doi: 10.1111/jdv.12772. Epub 2014 Oct 22.
PubMed 25338479Joly P, Maho-Vaillant M, Prost-Squarcioni C, Hebert V, Houivet E, Calbo S, Caillot F, Golinski ML, Labeille B, Picard-Dahan C, Paul C, Richard MA, Bouaziz JD, Duvert-Lehembre S, Bernard P, Caux F, Alexandre M, Ingen-Housz-Oro S, Vabres P, Delaporte E, Quereux G, Dupuy A, Debarbieux S, Avenel-Audran M, D'Incan M, Bedane C, Beneton N, Jullien D, Dupin N, Misery L, Machet L, Beylot-Barry M, Dereure O, Sassolas B, Vermeulin T, Benichou J, Musette P; French study group on autoimmune bullous skin diseases. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. Lancet. 2017 May 20;389(10083):2031-2040. doi: 10.1016/S0140-6736(17)30070-3. Epub 2017 Mar 22.
PubMed 28342637Lunardon L, Tsai KJ, Propert KJ, Fett N, Stanley JR, Werth VP, Tsai DE, Payne AS. Adjuvant rituximab therapy of pemphigus: a single-center experience with 31 patients. Arch Dermatol. 2012 Sep;148(9):1031-6. doi: 10.1001/archdermatol.2012.1522.
PubMed 22710375Ahmed AR, Spigelman Z, Cavacini LA, Posner MR. Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. N Engl J Med. 2006 Oct 26;355(17):1772-9. doi: 10.1056/NEJMoa062930.
PubMed 17065638Feldman RJ, Christen WG, Ahmed AR. Comparison of immunological parameters in patients with pemphigus vulgaris following rituximab and IVIG therapy. Br J Dermatol. 2012 Mar;166(3):511-7. doi: 10.1111/j.1365-2133.2011.10658.x. Epub 2012 Jan 19.
PubMed 21967407Ahmed AR, Kaveri S. Reversing Autoimmunity Combination of Rituximab and Intravenous Immunoglobulin. Front Immunol. 2018 Jul 18;9:1189. doi: 10.3389/fimmu.2018.01189. eCollection 2018.
PubMed 30072982Ahmed AR, Nguyen T, Kaveri S, Spigelman ZS. First line treatment of pemphigus vulgaris with a novel protocol in patients with contraindications to systemic corticosteroids and immunosuppressive agents: Preliminary retrospective study with a seven year follow-up. Int Immunopharmacol. 2016 May;34:25-31. doi: 10.1016/j.intimp.2016.02.013. Epub 2016 Feb 23.
PubMed 26919279Boulard C, Duvert Lehembre S, Picard-Dahan C, Kern JS, Zambruno G, Feliciani C, Marinovic B, Vabres P, Borradori L, Prost-Squarcioni C, Labeille B, Richard MA, Ingen-Housz-Oro S, Houivet E, Werth VP, Murrell DF, Hertl M, Benichou J, Joly P; International Pemphigus Study Group. Calculation of cut-off values based on the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Pemphigus Disease Area Index (PDAI) pemphigus scoring systems for defining moderate, significant and extensive types of pemphigus. Br J Dermatol. 2016 Jul;175(1):142-9. doi: 10.1111/bjd.14405. Epub 2016 Apr 3.
PubMed 26800395US Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Common terminology criteria for Adverse Events (CTCAE), version 5.0: Nov 27, 2017.
Murrell DF, Pena S, Joly P, Marinovic B, Hashimoto T, Diaz LA, Sinha AA, Payne AS, Daneshpazhooh M, Eming R, Jonkman MF, Mimouni D, Borradori L, Kim SC, Yamagami J, Lehman JS, Saleh MA, Culton DA, Czernik A, Zone JJ, Fivenson D, Ujiie H, Wozniak K, Akman-Karakas A, Bernard P, Korman NJ, Caux F, Drenovska K, Prost-Squarcioni C, Vassileva S, Feldman RJ, Cardones AR, Bauer J, Ioannides D, Jedlickova H, Palisson F, Patsatsi A, Uzun S, Yayli S, Zillikens D, Amagai M, Hertl M, Schmidt E, Aoki V, Grando SA, Shimizu H, Baum S, Cianchini G, Feliciani C, Iranzo P, Mascaro JM Jr, Kowalewski C, Hall R, Groves R, Harman KE, Marinkovich MP, Maverakis E, Werth VP. Diagnosis and management of pemphigus: Recommendations of an international panel of experts. J Am Acad Dermatol. 2020 Mar;82(3):575-585.e1. doi: 10.1016/j.jaad.2018.02.021. Epub 2018 Feb 10.
PubMed 29438767Liu KSH, Seto WK, Lau EHY, Wong DK, Lam YF, Cheung KS, Mak LY, Ko KL, To WP, Law MWK, Wu JT, Lai CL, Yuen MF. A Territorywide Prevalence Study on Blood-Borne and Enteric Viral Hepatitis in Hong Kong. J Infect Dis. 2019 May 24;219(12):1924-1933. doi: 10.1093/infdis/jiz038.
PubMed 30668746Seto WK, Chan TS, Hwang YY, Wong DK, Fung J, Liu KS, Gill H, Lam YF, Lie AK, Lai CL, Kwong YL, Yuen MF. Hepatitis B reactivation in patients with previous hepatitis B virus exposure undergoing rituximab-containing chemotherapy for lymphoma: a prospective study. J Clin Oncol. 2014 Nov 20;32(33):3736-43. doi: 10.1200/JCO.2014.56.7081. Epub 2014 Oct 6.
PubMed 25287829Tsai YF, Yang CI, Du JS, Lin MH, Tang SH, Wang HC, Cho SF, Liu YC, Su YC, Dai CY, Hsiao HH. Rituximab increases the risk of hepatitis B virus reactivation in non-Hodgkin lymphoma patients who are hepatitis B surface antigen-positive or have resolved hepatitis B virus infection in a real-world setting: a retrospective study. PeerJ. 2019 Sep 9;7:e7481. doi: 10.7717/peerj.7481. eCollection 2019.
PubMed 31565551
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of IVIG in Combination With Rituximab VS Rituximab as the First Line Treatment of Pemphigus
- ClinicalTrials.gov ID
- NCT04400994
- Acronym / sponsor ID
- UW19-671
- Conditions
- Pemphigus
- Keywords
- Pemphigus, intravenous immunoglobulins, rituximab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 20 participants (actual)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- 20 Jun 2020 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 26 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pemphigus is a rare acquired autoimmune disease in which immunoglobulin G (IgG) antibodies target desmosomal proteins to produce intraepithelial, and mucocutaneous blisters. It is potentially fatal and the average mortality of pemphigus vulgaris (PV) was 75% before the introduction of corticosteroids in the early 1950s.
Traditionally, treatment of pemphigus included high dose systemic corticosteroids with or without adjuvant immunosuppressants. However; the prolonged use of high dose steroids carries significant side effects. A recent randomized trial has proved the efficacy of Rituximab, a monoclonal anti-CD20 antibody against B-lymphocytes, as an efficacious therapy for pemphigus. Early use of rituximab was associated with better clinical outcomes, hence combination treatment of rituximab and intravenous immunoglobulins (IVIG) has shown to be effective for refractory pemphigus cases and can potentially induce long-term complete remission and lower risks infectious complications.
In this study, investigators will evaluate the efficacy and safety of early use of rituximab with or without IVIG in patients with moderate to severe pemphigus using protocols that were similar to those previously published, investigators will also aim to measure the impact of health care economics and in doing so, assess the cost and benefits of both treatment arms.
Detailed description
Pemphigus is a rare acquired autoimmune disease in which immunoglobulin G (IgG) antibodies target desmosomal proteins to produce intraepithelial, and mucocutaneous blisters. It is potentially fatal and the average mortality of pemphigus vulgaris (PV) was 75% before the introduction of corticosteroids in the early 1950s.
Traditionally, treatment of pemphigus included high dose systemic corticosteroids with or without adjuvant immunosuppressants. However; the prolonged use of high dose steroids carries significant side effects. A recent randomized trial has proved the efficacy of Rituximab, a monoclonal anti-CD20 antibody against B-lymphocytes, as an efficacious therapy for pemphigus. Furthermore, early use of rituximab was associated with associated with better clinical outcomes. Moreover, combination treatment of rituximab and intravenous immunoglobulins (IVIG) has shown to be effective for refractory pemphigus cases and can potentially induce long-term complete remission and lower risks infectious complications.
Cost effectiveness is an important issue and while combination of IVIG and rituximab has been advocated, the cost of such treatment is substantial and whether it poses any benefit over rituximab alone, or with other more conventional immunosuppressive agents, has not been established. Both treatment approaches have been previously published in high impact journals.
In this study, investigators aim to evaluate the efficacy and safety of early use of rituximab with or without IVIG in patients with moderate to severe pemphigus using protocols that were similar to those previously published. Apart from complete remission and adverse effects, investigators will also aim to measure the impact of health care economics and in doing so, assess the cost and benefits of both treatment arms.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rituximab only | Active comparator | Drug: Rituximab* Rituximab infusion 375mg/m2 body surface area (BSA) weekly for 4 weeks from baseline (week 0, 1, 2, 3) * Rituximab infusion 375mg/m2 BSA weekly for 4 weeks at week 24 (week 24, 25, 26, 27) * Rituximab infusion 375mg/m2 BSA weekly for 2 weeks at week 52 (week 52, 53) * Rituximab infusion 375mg/m2 BSA weekly for 4 weeks at week 76 (week 76, 77) * A total of 12 doses of rituximab will be given in 55 weeks |
| Rituximab and IVIG | Experimental | Drug: Rituximab, Other: IVIg* Rituximab (375 mg/m2 BSA) once a week for 4 weeks (week 1, 2, 3); * Week 4: Rituximab + IVIG 2g per kg * Week 5, 6, 7: Above treatment repeated for 2nd cycle, infusion of rituximab (375 mg/m2 BSA) once a week for 4 weeks (week 5, 6, 7); * Week 8: Rituximab + IVIG 2g/kg * In months 3, 4, 5, 6, patients received a single infusion of rituximab (375 mg/m2 BSA) plus infusion of 2g/kg IVIG * Thus in 6-month period patients received a total of 12 infusions of rituximab and 7 infusions of IVIG * If a patient was clinically free of disease at end of 6 months, additional infusions of IVIG will be given at week 30, 38, 48, 60 and 76 * A total of 12 doses of rituximab and 12 cycles of IVIG will be given |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Written informed consent obtained from patient
- Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
- Newly or recently diagnosed (less than 18 months) diagnosed pemphigus vulgaris or pemphigus foliaceus based on clinical features; histological features of acantholysis via skin or mucosal biopsy; and intercellular staining pattern of indirect immunofluorescence or serological detection of DSG 1 or DSG 3 by enzyme-linked immunosorbent assay (ELISA)
- Moderate to severe active disease, as defined by overall PDAI >= 15 or skin involvement BSA>= 5%. 9 [Annex 1]
- Receiving standard-of-care oral prednisolone up to 1.5 mg/kg/day
Key exclusion criteria (27 listed)
- Age <18 or >75
- Pregnant women or nursing mother
- Already diagnosed pemphigus patients diagnosed > 18 months
- Non-consenting patients, or patient who cannot be followed up regularly
- Patient with history of serious allergy or anaphylactic reaction to monoclonal antibody treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabAlso: MabTheraRituximab would be given intravenously. * IV Rituximab is prediluted at a dose of 500mg in 500ml of 0.9% normal saline (i.e. 1:1 dilution, 1 mg/ml) * Initial infusion rate starts at a rate of 50mg/hr (50ml/hr) * If no hypersensitivity/anaphylaxis reaction occurs, increase infusion rate in 50mg/hr (50 ml/hr) increments every 30 minutes * Maximum infusion rate is 400 mg/hr (400 ml/hr) * Subsequent infusion: start at rate of 100mg/hr (100 ml/hr), increase 100mg/hr (100 ml/hr) increments every 30 minutes * Monitor temperature, BP HR, respiratory rate and SpO2 every 30 minutes | Drug | Rituximab and IVIG, Rituximab only |
| IVIgAlso: PrivigenIVIg would be given in combination with Rituximab intravenously. Infusion plan of IVIg: 0 min: 50ml/hour 15 min: 75ml/hour 30 min: 100ml/hour 45 min: 125ml/hour 60 min: 150ml/hour 75 min \& beyond: 180ml/hour | Other | Rituximab and IVIG |
Primary outcome
relapse-free complete remission
Time frame: From baseline up to 208 weeks
Percentage of participants who achieve relapse-free complete remission
10 secondary outcomes
Time to protocol defined disease flare
Time frame: From baseline up to 208 weeks
Duration of complete remission
Time frame: From baseline up to 208 weeks
Number of protocol defined disease flares
Time frame: From baseline up to 208 weeks
Time to initial complete remission
Time frame: From baseline up to 208 weeks
Change in health-related quality of life: Dermatology Life Quality Index (DLQI) Score
Time frame: Baseline, Week 4, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192
Occurrence of severe treatment adverse events
Time frame: Baseline, week 4, 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192
Blood DSG 1 and 3 levels
Time frame: Baseline week 0, week 4, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192
Blood lymphocyte level (CBC)
Time frame: Baseline week 0, week 4, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192
Blood CD19/20 mean B cell counts percentage
Time frame: Week 0, week 4, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192
Number of rescue therapy given
Time frame: Baseline up to Week 208
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2025.
- Background: PubMed 29192996Harman KE, Brown D, Exton LS, Groves RW, Hampton PJ, Mohd Mustapa MF, Setterfield JF, Yesudian PD. British Association of Dermatologists' guidelines for the management of pemphigus vulgaris 2017. Br J Dermatol. 2017 Nov;177(5):1170-1201. doi: 10.1111/bjd.15930. No abstract available.
- Background: PubMed 25338479Hertl M, Jedlickova H, Karpati S, Marinovic B, Uzun S, Yayli S, Mimouni D, Borradori L, Feliciani C, Ioannides D, Joly P, Kowalewski C, Zambruno G, Zillikens D, Jonkman MF. Pemphigus. S2 Guideline for diagnosis and treatment--guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV). J Eur Acad Dermatol Venereol. 2015 Mar;29(3):405-14. doi: 10.1111/jdv.12772. Epub 2014 Oct 22.
- Background: PubMed 28342637Joly P, Maho-Vaillant M, Prost-Squarcioni C, Hebert V, Houivet E, Calbo S, Caillot F, Golinski ML, Labeille B, Picard-Dahan C, Paul C, Richard MA, Bouaziz JD, Duvert-Lehembre S, Bernard P, Caux F, Alexandre M, Ingen-Housz-Oro S, Vabres P, Delaporte E, Quereux G, Dupuy A, Debarbieux S, Avenel-Audran M, D'Incan M, Bedane C, Beneton N, Jullien D, Dupin N, Misery L, Machet L, Beylot-Barry M, Dereure O, Sassolas B, Vermeulin T, Benichou J, Musette P; French study group on autoimmune bullous skin diseases. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. Lancet. 2017 May 20;389(10083):2031-2040. doi: 10.1016/S0140-6736(17)30070-3. Epub 2017 Mar 22.
- Background: PubMed 22710375Lunardon L, Tsai KJ, Propert KJ, Fett N, Stanley JR, Werth VP, Tsai DE, Payne AS. Adjuvant rituximab therapy of pemphigus: a single-center experience with 31 patients. Arch Dermatol. 2012 Sep;148(9):1031-6. doi: 10.1001/archdermatol.2012.1522.
- Background: PubMed 17065638Ahmed AR, Spigelman Z, Cavacini LA, Posner MR. Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. N Engl J Med. 2006 Oct 26;355(17):1772-9. doi: 10.1056/NEJMoa062930.
- Background: PubMed 21967407Feldman RJ, Christen WG, Ahmed AR. Comparison of immunological parameters in patients with pemphigus vulgaris following rituximab and IVIG therapy. Br J Dermatol. 2012 Mar;166(3):511-7. doi: 10.1111/j.1365-2133.2011.10658.x. Epub 2012 Jan 19.
- Background: PubMed 30072982Ahmed AR, Kaveri S. Reversing Autoimmunity Combination of Rituximab and Intravenous Immunoglobulin. Front Immunol. 2018 Jul 18;9:1189. doi: 10.3389/fimmu.2018.01189. eCollection 2018.
- Background: PubMed 26919279Ahmed AR, Nguyen T, Kaveri S, Spigelman ZS. First line treatment of pemphigus vulgaris with a novel protocol in patients with contraindications to systemic corticosteroids and immunosuppressive agents: Preliminary retrospective study with a seven year follow-up. Int Immunopharmacol. 2016 May;34:25-31. doi: 10.1016/j.intimp.2016.02.013. Epub 2016 Feb 23.
- Background: PubMed 26800395Boulard C, Duvert Lehembre S, Picard-Dahan C, Kern JS, Zambruno G, Feliciani C, Marinovic B, Vabres P, Borradori L, Prost-Squarcioni C, Labeille B, Richard MA, Ingen-Housz-Oro S, Houivet E, Werth VP, Murrell DF, Hertl M, Benichou J, Joly P; International Pemphigus Study Group. Calculation of cut-off values based on the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Pemphigus Disease Area Index (PDAI) pemphigus scoring systems for defining moderate, significant and extensive types of pemphigus. Br J Dermatol. 2016 Jul;175(1):142-9. doi: 10.1111/bjd.14405. Epub 2016 Apr 3.
- BackgroundUS Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Common terminology criteria for Adverse Events (CTCAE), version 5.0: Nov 27, 2017.
- Background: PubMed 29438767Murrell DF, Pena S, Joly P, Marinovic B, Hashimoto T, Diaz LA, Sinha AA, Payne AS, Daneshpazhooh M, Eming R, Jonkman MF, Mimouni D, Borradori L, Kim SC, Yamagami J, Lehman JS, Saleh MA, Culton DA, Czernik A, Zone JJ, Fivenson D, Ujiie H, Wozniak K, Akman-Karakas A, Bernard P, Korman NJ, Caux F, Drenovska K, Prost-Squarcioni C, Vassileva S, Feldman RJ, Cardones AR, Bauer J, Ioannides D, Jedlickova H, Palisson F, Patsatsi A, Uzun S, Yayli S, Zillikens D, Amagai M, Hertl M, Schmidt E, Aoki V, Grando SA, Shimizu H, Baum S, Cianchini G, Feliciani C, Iranzo P, Mascaro JM Jr, Kowalewski C, Hall R, Groves R, Harman KE, Marinkovich MP, Maverakis E, Werth VP. Diagnosis and management of pemphigus: Recommendations of an international panel of experts. J Am Acad Dermatol. 2020 Mar;82(3):575-585.e1. doi: 10.1016/j.jaad.2018.02.021. Epub 2018 Feb 10.
- Background: PubMed 30668746Liu KSH, Seto WK, Lau EHY, Wong DK, Lam YF, Cheung KS, Mak LY, Ko KL, To WP, Law MWK, Wu JT, Lai CL, Yuen MF. A Territorywide Prevalence Study on Blood-Borne and Enteric Viral Hepatitis in Hong Kong. J Infect Dis. 2019 May 24;219(12):1924-1933. doi: 10.1093/infdis/jiz038.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sze Man Wong, MBBS principal investigator
The University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab and IVIg in people with Pemphigus, run by The University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
relapse-free complete remission (time frame: From baseline up to 208 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04400994, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2025.