Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
100
Countries
1
Sites
3
Primary antibody deficiency: - Unclassified antibody deficiency (unPAD) - IgA deficiency - Specific polysaccharide antibody deficiency (SPAD) - IgG subclass deficiency (IgSD) - Common variable immunodeficiency (CVID) - Agammaglobulinemia (X-linked or otherwise)
To show the protective value and to measure cost effectiveness of higher Ig dosing on progression of lung disease in PAD.
Key facts
- Sponsor
- Universitair Medisch Centrum Utrecht
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Immune System Diseases [C20]
- Trial duration
- 12 Jul 2024 → 31 Mar 2026
- Decision date (initial)
- 2024-07-12
- Transition trial
- Yes
- Low-intervention
- Yes
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- CSL Behring · Takeda · ZonMw
External identifiers
- EU CT number
- 2024-513124-41-00
- EudraCT number
- 2021-005001-26
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
To show the protective value and to measure cost effectiveness of higher Ig dosing on progression of lung disease in PAD.
Secondary objectives 6
- The incidence of symptomatic lower pulmonary infections in PAD patients with high Ig replacement therapy dosing versus standard Ig replacement therapy dosing.
- Number of physician diagnosed lower respiratory tract infections in patients with high vs standard Ig replacement therapy dosing.
- Number of hospital admissions and duration of hospital admissions for pulmonary complications (ao exacerbations of bronchiectasis)
- Outcomes of pulmonary function tests (specifically: Total Lung Capacity (TLC), Forced Expiratory Volume after 1 second (FEV1), CO diffusion) on t=0 and t=2 years in all patients
- Days missed from work / school in patients with high vs standard Ig replacement therapy dosing.
- Total therapeutic and preventive costs
Conditions and MedDRA coding
Primary antibody deficiency: - Unclassified antibody deficiency (unPAD) - IgA deficiency - Specific polysaccharide antibody deficiency (SPAD) - IgG subclass deficiency (IgSD) - Common variable immunodeficiency (CVID) - Agammaglobulinemia (X-linked or otherwise)
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Age 8-60 years
- Diagnosis of Primary Antibody Deficiency / Common Variable Immunodeficiency Disorder (see Appendix I protocol)
- Indication for immunoglobulin replacement therapy and/or treated with immunoglobulin replacement therapy
- Current IgG dosing 0.25 - 0.6 gr / kg / 3-4 weeks
- Receiving treatment and follow-up for PAD by a physician in one of the participating centers
- Written informed consent
Exclusion criteria 3
- Diagnosis of Combined Immunodeficiency (CID) disease at onset of study (see Appendix 1). Explanation: Combined Immunodeficiency is featured by the occurrence of more viral infections and reactivations and thus less comparable to PAD.
- Severe pulmonary disease, determined by an independent radiologist: a. Baseline AD score > 7 and/or ILD score > 5, in combination with: i. Saccular bronchiectasis on CT scan, or; ii. Clinical diagnosis of severe respiratory insufficiency ( (defined as: saturations in room air <92%, and/ or oxygen dependency). b. Baseline pulmonary function (FEV1 and FVC) <70% expected for age and body weight / length)
- Active smoker
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Difference in mean AD and ILD scores (as measured with CT scanning) between t=0 and t=2 years in patients with standard vs higher Ig replacement therapy dosing.
Secondary endpoints 8
- Number of upper- and lower respiratory tract infections before onset of study and during study, i.e.: Sino pulmonary disease, otitis, pneumonia, collected by study CRF's.
- Pulmonary symptoms will be evaluated on a daily basis (during two periods of 2 months) using a diary that can be directly entered in Castor.
- Days missed from school and work due to infections, measured by the PCQ (productivity cost questionnaire) instrument.
- Quality of life, measured with the EQ-5D questionnaire
- Ig dosing and IgG trough levels in intervention and in control group
- Total health costs (consisting of costs for health care professional visits, medication, hospitalizations, imaging and biochemical investigations) in intervention and control group, collected from electronic patient files.
- Immunological laboratory phenotype, collected from electronic patient files.
- Adverse events: reporting and monitoring of patients and Adverse Events (AEs), Serious Adverse Events (SAEs) and Suspected Unexpected Serious Adverse Reaction (SUSARs) will be done by an independent monitor.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 10
Gammanorm, 165 mg/ml, oplossing voor injectie
PRD1593998 · Product
- Active substance
- Human Normal Immunoglobulin
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 800 mg/kg milligram(s)/kilogram
- Max total dose
- 800 mg/kg milligram(s)/kilogram
- Max treatment duration
- 1000000 Month(s)
- Authorisation status
- Authorised
- ATC code
- J06BA01 — IMMUNOGLOBULINS, NORMAL HUMAN, FOR EXTRAVASCULAR ADM.
- Marketing authorisation
- BE451377
- MA holder
- OCTAPHARMA BENELUX S.A.
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Octagam 10%, oplossing voor infusie
PRD319321 · Product
- Active substance
- Human Normal Immunoglobulin (IV)
- Substance synonyms
- HUMAN NORMAL IMMUNOGLOBULIN FOR INTRAVENOUS ADMINISTRATION, HUMAN NORMAL IMMUNOGLOBULIN (IVIG)
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 800 mg/kg milligram(s)/kilogram
- Max total dose
- 800 mg/kg milligram(s)/kilogram
- Max treatment duration
- 1000000 Month(s)
- Authorisation status
- Authorised
- ATC code
- J06BA02 — IMMUNOGLOBULINS, NORMAL HUMAN, FOR INTRAVASCULAR ADM.
- Marketing authorisation
- RVG 104459
- MA holder
- OCTAPHARMA GMBH
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Nanogam 100 mg/ml oplossing voor infusie
PRD5655545 · Product
- Active substance
- Human Normal Immunoglobulin
- Substance synonyms
- IMMUNOGLOBULIN HUMAN NORMAL
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 800 mg/kg milligram(s)/kilogram
- Max total dose
- 800 mg/kg milligram(s)/kilogram
- Max treatment duration
- 1000000 Month(s)
- Authorisation status
- Authorised
- ATC code
- J06BA02 — IMMUNOGLOBULINS, NORMAL HUMAN, FOR INTRAVASCULAR ADM.
- Marketing authorisation
- BE518924
- MA holder
- PROTHYA BIOSOLUTIONS NETHERLANDS B.V.
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
KIOVIG 100 mg/ml solution for infusion
PRD7734933 · Product
- Active substance
- Human Normal Immunoglobulin
- Substance synonyms
- IMMUNOGLOBULIN HUMAN NORMAL
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 800 mg/kg milligram(s)/kilogram
- Max total dose
- 800 mg/kg milligram(s)/kilogram
- Max treatment duration
- 1000000 Month(s)
- Authorisation status
- Authorised
- ATC code
- J06BA02 — IMMUNOGLOBULINS, NORMAL HUMAN, FOR INTRAVASCULAR ADM.
- Marketing authorisation
- EU/1/05/329/001
- MA holder
- TAKEDA MANUFACTURING AUSTRIA AG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
HyQvia 100 mg/ml solution for infusion for subcutaneous use
PRD3237756 · Product
- Active substance
- Human Normal Immunoglobulin
- Substance synonyms
- IMMUNOGLOBULIN HUMAN NORMAL
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 800 mg/kg milligram(s)/kilogram
- Max total dose
- 800 mg/kg milligram(s)/kilogram
- Max treatment duration
- 1000000 Month(s)
- Authorisation status
- Authorised
- ATC code
- J06BA — IMMUNOGLOBULINS, NORMAL HUMAN
- Marketing authorisation
- EU/1/13/840/001
- MA holder
- BAXALTA INNOVATIONS GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
GAMMAGARD S/D 5,0 g, poeder en oplosmiddel voor oplossing voor infusie.
PRD3332247 · Product
- Active substance
- Human Normal Immunoglobulin
- Substance synonyms
- IMMUNOGLOBULIN HUMAN NORMAL
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 800 mg/kg milligram(s)/kilogram
- Max total dose
- 800 mg/kg milligram(s)/kilogram
- Max treatment duration
- 1000000 Month(s)
- Authorisation status
- Authorised
- ATC code
- J06BA02 — IMMUNOGLOBULINS, NORMAL HUMAN, FOR INTRAVASCULAR ADM.
- Marketing authorisation
- RVG 17033
- MA holder
- BAXALTA INNOVATIONS GMBH
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Cuvitru 200 mg/ml oplossing voor subcutane injectie
PRD7444791 · Product
- Active substance
- Human Normal Immunoglobulin
- Substance synonyms
- IMMUNOGLOBULIN HUMAN NORMAL
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 150 mg/kg milligram(s)/kilogram
- Max total dose
- 1000 mg/kg milligram(s)/kilogram
- Max treatment duration
- 1000000 Month(s)
- Authorisation status
- Authorised
- ATC code
- J06BA01 — IMMUNOGLOBULINS, NORMAL HUMAN, FOR EXTRAVASCULAR ADM.
- Marketing authorisation
- BE543644
- MA holder
- BAXALTA INNOVATIONS GMBH
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Hizentra 200 mg/ml solution for subcutaneous injection
PRD332134 · Product
- Active substance
- Human Normal Immunoglobulin
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 800 mg/kg milligram(s)/kilogram
- Max total dose
- 800 mg/kg milligram(s)/kilogram
- Max treatment duration
- 1000000 Month(s)
- Authorisation status
- Authorised
- ATC code
- J06BA01 — IMMUNOGLOBULINS, NORMAL HUMAN, FOR EXTRAVASCULAR ADM.
- Marketing authorisation
- EU/1/11/687/001
- MA holder
- CSL BEHRING GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Privigen 100 mg/ml solution for infusion
PRD339234 · Product
- Active substance
- Human Normal Immunoglobulin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 800 mg/kg milligram(s)/kilogram
- Max total dose
- 800 mg/kg milligram(s)/kilogram
- Max treatment duration
- 1000000 Month(s)
- Authorisation status
- Authorised
- ATC code
- J06BA02 — IMMUNOGLOBULINS, NORMAL HUMAN, FOR INTRAVASCULAR ADM.
- Marketing authorisation
- EU/1/08/446/001
- MA holder
- CSL BEHRING GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
CUTAQUIG 165 mg/mL, solution injectable
PRD7184381 · Product
- Active substance
- Human Normal Immunoglobulin
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 800 mg/kg milligram(s)/kilogram
- Max total dose
- 800 mg/kg milligram(s)/kilogram
- Max treatment duration
- 1000000 Month(s)
- Authorisation status
- Authorised
- ATC code
- J06BA01 — IMMUNOGLOBULINS, NORMAL HUMAN, FOR EXTRAVASCULAR ADM.
- Marketing authorisation
- 34009 301 732 3 7
- MA holder
- OCTAPHARMA FRANCE
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Universitair Medisch Centrum Utrecht
- Sponsor organisation
- Universitair Medisch Centrum Utrecht
- Address
- Heidelberglaan 100
- City
- Utrecht
- Postcode
- 3584 CX
- Country
- Netherlands
Scientific contact point
- Organisation
- Universitair Medisch Centrum Utrecht
- Contact name
- dr. J.M. van Montfrans
Public contact point
- Organisation
- Universitair Medisch Centrum Utrecht
- Contact name
- dr. J.M. van Montfrans
Locations
1 EU/EEA country · 3 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ended | 100 | 3 |
| Rest of world | — | 0 | — |
Investigational sites
Universitair Medisch Centrum Utrecht
Pediatric Immunology and Infectious Diseases, Heidelberglaan 100, 3584 CX, Utrecht
Radboud universitair medisch centrum / RADBOUDUMC
Internal Medicine, division Infectious Diseases and Immunology, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Internal Medicine, division Immunology, Dr. Molewaterplein 60, 3015 GJ, Rotterdam
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2024-07-12 | 2026-03-31 | 2024-07-12 | 2024-07-12 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 17 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-513124-41-00_V4_2_Feb2026_CLEAN_Redacted | 4.2 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_Blank document | 1 |
| Subject information and informed consent form (for publication) | L1_Proefpersoneninformatie IPAD trial Adolsecenten | 1.1 |
| Subject information and informed consent form (for publication) | L1_Proefpersoneninformatie IPAD trial Ouders en Vertegenwoordigers | 1.1 |
| Subject information and informed consent form (for publication) | L1_Proefpersoneninformatie IPAD trial Volwassenen | 1.1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SMPC Cutaquig | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SMPC Cuvitru | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SMPC Gammagard | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SMPC Gammanorm | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SMPC Hizentra | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SMPC HyQvia | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SMPC Kiovig | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SMPC Nanogam | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SMPC Octagam | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SMPC Privigen | 1 |
| Synopsis of the protocol (for publication) | D1_NL_EN_Protocol_synopsis_2024-513124-41-00 | 1.0 |
| Synopsis of the protocol (for publication) | D1_NL_NL_Protocol_synopsis_2024-513124-41-00 | 1.0 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-08 | Netherlands | Acceptable with conditions 2024-07-12
|
2024-07-12 |
| 2 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-12-29 | Netherlands | Acceptable 2026-03-18
|
2026-03-18 |