Granulomatosis With Polyangiitis (GPA)Phase 2NCT03712345
Safety and Efficacy Study of IFX-1 in add-on to Standard of Care in GPA and MPA
A Phase 2 study testing IFX-1 low dose and IFX-1 high dose in people with Granulomatosis With Polyangiitis (GPA) and Microscopic Polyangiitis (MPA), run by InflaRx GmbH at 38 sites in 2 countries.
Trial summary
The purpose of this study is to investigate the safety and tolerability of two dose regimens of IFX-1 as add-on to standard of care (SOC) in subjects with GPA and MPA compared with placebo. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Granulomatosis With Polyangiitis (GPA), Microscopic Polyangiitis (MPA)
- What is being tested?
- IFX-1 low dose and IFX-1 high dose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 38 sitesin 2 countries
- Study dates
- 15 Oct 2018to 3 May 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, ≥18 years of age.
- Diagnosis of GPA or MPA according to the definitions of the Chapel Hill Consensus Conference.
- Have at least one "major" item, or at least three other items, or at least two renal items on the Birmingham Vasculitis Activity Score (BVAS) Version 3.0.
- New or relapsed GPA or MPA that require treatment with CYC or RTX plus GCs.
Who cannot join
- Any other multisystem autoimmune disease
- Requires mechanical ventilation because of alveolar hemorrhage at Screening.
- Human immunodeficiency virus, hepatitis B, or hepatitis C viral screening test showing evidence of active or chronic viral infection at Screening or a documented history of the human immunodeficiency virus, hepatitis B, or hepatitis C.
- Received CYC or RTX 12 weeks before Screening; if on azathioprine (AZA), methotrexate (MTX), mycophenolate mofetil (MMF), or mycophenolate sodium (MPS) at the time of Screening, these drugs must be withdrawn prior to receiving CYC or RTX.
- Received more than 3 g cumulative high dose intravenous GCs within 4 weeks before Screening.
- On an oral dose of a GC of more than 10 mg prednisone equivalent at Screening or for more than 6 weeks before Screening.
Show all 9Show fewer
- Received a CD20 inhibitor, anti-tumor necrosis factor treatment, abatacept, alemtuzumab, any other experimental or biological therapy, intravenous immunoglobulin or plasma exchange, antithymocyte globulin, or required dialysis within 12 weeks before Screening.
- Received a live vaccination within 4 weeks before Screening or planned between Screening and Week 24.
- Female subjects of childbearing potential unwilling or unable to use a highly effective method of contraception (pearl index <1%) such as complete sexual abstinence, combined oral contraceptive, vaginal hormone ring, transdermal contraceptive patch, contraceptive implant, or depot contraceptive injection in combination with a second method of contraception such as condom, cervical cap, or diaphragm with spermicide during the study and for at least 4 weeks after last administration of IFX-1 (timeframes for SOC have to be considered as described in the respective Prescribing Information).
Trial locations and contacts
38 sites in 2 countries.
38 sites in 2 countries
United States33 sites
University of New Mexico
Albuquerque, New Mexico, 87131
University Of MI Medcl Ctr-RHU
Ann Arbor, Michigan, 48109
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224
Massachusetts General Hospital
Boston, Massachusetts, 02114
BRCR Medical Center, Inc.
Camp Hill, Pennsylvania, 17011
UNC Kidney Center, UNC-CH Division of Nephrology and Hypertension
Chapel Hill, North Carolina, 27599-7155
UVA University Physicians Charlottesville
Charlottesville, Virginia, 22903
Rush University Medical Center
Chicago, Illinois, 60612
Ohio State University Clinical Trials Management Office
Columbus, Ohio, 43203
Adriana Pop Moody Clinic PA
Corpus Christi, Texas, 78404
Texas Health Resources
Dallas, Texas, 75287
Henry Ford Hospital
Detroit, Michigan, 48084
Science Connections, LLC
Doral, Florida, 33166
Altoona Center for Clinical Research, P.C.
Duncansville, Pennsylvania, 16635
Texas Research Institute
Fort Worth, Texas, 76104
Pioneer Research Solutions, Inc.
Houston, Texas, 77099
University of Kansas Medical Center Research Institute, Inc.
Kansas City, Kansas, 66160
Loma Linda University Clinical Trial Center
Loma Linda, California, 92354
University of Miami
Miami, Florida, 33136
University of Minnesota
Minneapolis, Minnesota, 55414
Trinity Medical Group
Minot, North Dakota, 58701
West Virginia University
Morgantown, West Virginia, 26506
Northwell Health, LLC PRIME
New Hyde Park, New York, 11042
Hospital for Special Surgery
New York, New York, 10021
Low Country Rheumatology, PA
North Charleston, South Carolina, 29406
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Oregon Health & Science University
Portland, Oregon, 97239
Rhode Island Hospital
Providence, Rhode Island, 02903
Mayo Clinic
Rochester, Minnesota, 55905
University of Rochester Medical Center - Strong Memorial Hospital
Rochester, New York, 14642
Mayo Clinic Scottsdale
Scottsdale, Arizona, 85259
LSU Health Sciences Center Shreveport
Shreveport, Louisiana, 71103
Washington University
St Louis, Missouri, 63110
Canada5 sites
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7
St. Josephs Healthcare
Hamilton, Ontaria, L8N 4A6
CHUM Centre de Recherche
Québec, Quebec, H2X 0A9
Mount Sinai Hospital
Toronto, Ontario, M5G 1X5
Centre de Recherche Musculo-Squelettique
Trois-Rivières, Quebec, G8Z1Y2
About this study
Official title: Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase II Efficacy and Safety Study of IFX-1 in Add-On to Standard of Care in Granulomatosis With Polyangiitis (GPA) and Microscopic Polyangiitis (MPA)
The purpose of this study is to investigate the safety and tolerability of two dose regimens of IFX-1 as add-on to standard of care (SOC) in subjects with GPA and MPA compared with placebo.
Read the detailed description
Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are related systemic v anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a potentially life-threatening disease.
GPA is a necrotizing vasculitis predominantly involving small- to medium-sized vessels (e.g., capillaries, venules, arterioles, arteries, and veins). MPA is a necrotizing vasculitis that primarily affects capillaries, venules, or arterioles, most commonly manifesting as necrotizing glomerulonephritis and/or pulmonary capillaritis. MPA.
Primed neutrophils are activated by ANCA and generate C5a that engages C5a receptors on neutrophils. Therefore, patients with ANCA-related disease have elevated plasma and urine levels of C5a in active disease and not in remission.
IFX-1 is a monoclonal antibody specifically binding to the soluble human complement split product C5a and the resulting nearly complete blockade of C5a-induced biological effects may be effective in the treatment of subjects with AAV.
- Being tested
- IFX-1 low dose, IFX-1 high dose, Placebo
- Keywords
- Granulomatosis with Polyangiitis (GPA), Microscopic Polyangiitis (MPA), IFX-1, ANCA, AAV
- Medical subject headings
- Granulomatosis with Polyangiitis, Microscopic Polyangiitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IFX-1 low doseDrug
Also called CaCP29
Single IV infusions of IFX-1
IFX-1 high doseDrug
Also called CaCP29
Single IV infusions of IFX-1
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| IFX-1 low dose | Experimental | Will receive IFX-1 low dose regimen diluted in sodium chloride solution Receives: Drug: IFX-1 low dose |
| IFX-1 high dose | Experimental | Will receive IFX-1 high dose regimen diluted in sodium chloride solution Receives: Drug: IFX-1 high dose |
| Placebo | Placebo comparator | Will receive placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and Percentage of Participants With at Least One TEAE Per Treatment Group.
Number and percentage of participants who experience at least one treatment-emergent adverse event (TEAE) per treatment group.
Measured: Week 24
Secondary outcomes (7)
Percentage of Participants Achieving Clinical Response
Efficacy Endpoint based on clinical response evaluated through BVAS. Clinical response is defined as a reduction in BVAS of ≥50% and no worsening in any body system and no administration of rescue medication prior to the response assessment.
Measured: Week 16
Percentage of Participants With Clinical Remission (BVAS = 0)
Efficacy Endpoint that evaluates participants with complete remission
Measured: Week 16
IFX-1 Concentration Pre-dose
Assess the pharmacokinetic of the investigational medicinal product.
Measured: Week 16
IFX 1 Concentration at Predose (0 Hours), After the End of the Infusion (+10minutes), and at 2, 6, 24, and 48 Hours After the Start of the Infusion for Participants in the PK Substudy
Analyze the IMP plasma concentration using a PK model: IFX 1 concentration at predose (0 hours), after the end of the infusion (+10minutes), and at 2, 6, 24, and 48 hours after the start of the infusion for participants in the PK substudy
Measured: Weeks 1, 4 and 16
C5a Plasma Concentration
Pharmacodynamic parameter concentration
Measured: Week 16
IFX-1 Blocking Activity 2.5 nM
Pharmacodynamic Parameter of IFX-1 blocking activity 2.5 nM
Measured: Week 16
IFX-1 Blocking Activity 10 nM
Pharmacodynamic Parameter of IFX-1 blocking activity 10 nM
Measured: Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2018
- Study start15 Oct 2018
- Primary completion10 Sep 2020
- Study completion3 May 2021
Why it stopped: Due to COVID-19 pandemic outbreak and its impact on overall study activities. All efforts were made to ensure that participants that were enrolled and/or were still in the study will continue to receive treatment and follow-up until study completion.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Granulomatosis With Polyangiitis (GPA)Studies of the same condition, open and under way.
- 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- InflaRx GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- IQVIA Pty Ltd
- Responsible party
- Sponsor
- Investigators
- Korinna Pilz, MD, MS, Study director, InflaRx GmbHPeter A. Merkel, MD, MPH, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03712345
- Sponsor's protocol ID
- IFX-1-P2.6
- Status last verified
- May 2022
- First submitted
- 16 Oct 2018
- Last updated
- 26 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Serling-Boyd N, Wallace ZS. Management of primary vasculitides with biologic and novel small molecule medications. Curr Opin Rheumatol. 2021 Jan;33(1):8-14. doi: 10.1097/BOR.0000000000000756.
PubMed 33164993
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase II Efficacy and Safety Study of IFX-1 in Add-On to Standard of Care in Granulomatosis With Polyangiitis (GPA) and Microscopic Polyangiitis (MPA)
- ClinicalTrials.gov ID
- NCT03712345
- Acronym / sponsor ID
- IFX-1-P2.6
- Keywords
- Granulomatosis with Polyangiitis (GPA), Microscopic Polyangiitis (MPA), IFX-1, ANCA, AAV
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to COVID-19 pandemic outbreak and its impact on overall study activities. All efforts were made to ensure that participants that were enrolled and/or were still in the study will continue to receive treatment and follow-up until study completion.
- Enrolment
- 20 participants (actual)
- Lead sponsor
- InflaRx GmbHIndustry (pharma, biotech, devices)
- Collaborators
- IQVIA Pty Ltd
- Study start
- 15 Oct 2018 (actual)
- Primary completion
- 10 Sep 2020 (actual)
- Study completion
- 3 May 2021 (actual)
- First posted
- 19 Oct 2018 (actual)
- Results
- Posted 26 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to investigate the safety and tolerability of two dose regimens of IFX-1 as add-on to standard of care (SOC) in subjects with GPA and MPA compared with placebo.
Detailed description
Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are related systemic v anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a potentially life-threatening disease.
GPA is a necrotizing vasculitis predominantly involving small- to medium-sized vessels (e.g., capillaries, venules, arterioles, arteries, and veins). MPA is a necrotizing vasculitis that primarily affects capillaries, venules, or arterioles, most commonly manifesting as necrotizing glomerulonephritis and/or pulmonary capillaritis. MPA.
Primed neutrophils are activated by ANCA and generate C5a that engages C5a receptors on neutrophils. Therefore, patients with ANCA-related disease have elevated plasma and urine levels of C5a in active disease and not in remission.
IFX-1 is a monoclonal antibody specifically binding to the soluble human complement split product C5a and the resulting nearly complete blockade of C5a-induced biological effects may be effective in the treatment of subjects with AAV.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| IFX-1 low dose | Experimental | Drug: IFX-1 low doseWill receive IFX-1 low dose regimen diluted in sodium chloride solution |
| IFX-1 high dose | Experimental | Drug: IFX-1 high doseWill receive IFX-1 high dose regimen diluted in sodium chloride solution |
| Placebo | Placebo comparator | Drug: PlaceboWill receive placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male or female, ≥18 years of age.
- Diagnosis of GPA or MPA according to the definitions of the Chapel Hill Consensus Conference.
- Have at least one "major" item, or at least three other items, or at least two renal items on the Birmingham Vasculitis Activity Score (BVAS) Version 3.0.
- New or relapsed GPA or MPA that require treatment with CYC or RTX plus GCs.
Key exclusion criteria (9 listed)
- Any other multisystem autoimmune disease
- Requires mechanical ventilation because of alveolar hemorrhage at Screening.
- Human immunodeficiency virus, hepatitis B, or hepatitis C viral screening test showing evidence of active or chronic viral infection at Screening or a documented history of the human immunodeficiency virus, hepatitis B, or hepatitis C.
- Received CYC or RTX 12 weeks before Screening; if on azathioprine (AZA), methotrexate (MTX), mycophenolate mofetil (MMF), or mycophenolate sodium (MPS) at the time of Screening, these drugs must be withdrawn prior to receiving CYC or RTX.
- Received more than 3 g cumulative high dose intravenous GCs within 4 weeks before Screening.
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 |
|---|---|---|
| IFX-1 low doseAlso: CaCP29Single IV infusions of IFX-1 | Drug | IFX-1 low dose |
| IFX-1 high doseAlso: CaCP29Single IV infusions of IFX-1 | Drug | IFX-1 high dose |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Number and Percentage of Participants With at Least One TEAE Per Treatment Group.
Time frame: Week 24
Number and percentage of participants who experience at least one treatment-emergent adverse event (TEAE) per treatment group.
7 secondary outcomes
Percentage of Participants Achieving Clinical Response
Time frame: Week 16
Percentage of Participants With Clinical Remission (BVAS = 0)
Time frame: Week 16
IFX-1 Concentration Pre-dose
Time frame: Week 16
IFX 1 Concentration at Predose (0 Hours), After the End of the Infusion (+10minutes), and at 2, 6, 24, and 48 Hours After the Start of the Infusion for Participants in the PK Substudy
Time frame: Weeks 1, 4 and 16
C5a Plasma Concentration
Time frame: Week 16
IFX-1 Blocking Activity 2.5 nM
Time frame: Week 16
IFX-1 Blocking Activity 10 nM
Time frame: Week 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33164993Serling-Boyd N, Wallace ZS. Management of primary vasculitides with biologic and novel small molecule medications. Curr Opin Rheumatol. 2021 Jan;33(1):8-14. doi: 10.1097/BOR.0000000000000756.
- 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.
Korinna Pilz, MD, MS study director
InflaRx GmbH
Peter A. Merkel, MD, MPH principal investigator
University of Pennsylvania
38 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IFX-1 low dose and IFX-1 high dose in people with Granulomatosis With Polyangiitis (GPA) and Microscopic Polyangiitis (MPA), run by InflaRx GmbH at 38 sites in 2 countries.
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 4 inclusion and 9 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: stopped early, as of the sponsor's last update on 26 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States, Canada. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 26 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number and Percentage of Participants With at Least One TEAE Per Treatment Group. (time frame: Week 24). 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 NCT03712345, which also lists 1 linked publication.
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 26 May 2022.