A clinical study to assess efficacy and safety of the human Anti-CD38 Antibody Felzartamab in IgA Nephropathy

• Register: EUCTR
• Last refreshed on: 3 June 2024
• Main ID: EUCTR2020-005054-19-DE
• Date of registration: 01/04/2021
• Prospective Registration: Yes
• Primary sponsor: Human Immunology Biosciences, Inc
• Public title: A clinical study to assess efficacy and safety of the human Anti-CD38 Antibody Felzartamab in IgA Nephropathy
• Scientific title: A Double Blind, Randomized, Placebo-Controlled, Multicenter Phase IIa, Clinical Trial to Assess Efficacy and Safety of the Human Anti-CD38 Antibody Felzartamab in IgA Nephropathy - IGNAZ
• Date of first enrolment: 16/08/2021
• Target sample size: 48
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-005054-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Bulgaria, Canada, Czech Republic, Czechia, Georgia, Germany, Japan, Korea, Republic of, Malaysia, Philippines, Serbia, Spain, Taiwan, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Operations
• Affiliation: Human Immunology Biosciences, Inc

• Name: Clinical Operations
• Affiliation: Human Immunology Biosciences, Inc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients = 18 to = 80 years (at date of signing the informed consent form [ICF]), but at least of legal age in the given country.
2. Biopsy confirmed diagnosis of IgAN within the past 8 years prior to signature of the ICF
3. Proteinuria at screening visit = 1.0 g/d
4. Treatment with an angiotensin-converting enzyme inhibitor (ACEi) and/or angiotensin receptor blocker (ARB) at maximum doses or maximally tolerated doses for = 3 months prior to date of informed consent and adequate blood pressure (BP) control (recommended BP is < 125 mm Hg systolic and < 75 mm Hg diastolic).
In case a patient is intolerant to even a very low dose of either ACEi or ARB therapy, approval for participation in the trial has to be obtained from the Medical Monitor prior to randomization.
5. A female of childbearing potential (FCBP) is only eligible to participate if she is not pregnant, not breast feeding, and agrees to follow the contraceptive guidance during the treatment period and for at least 3 months after the last dose of Felzartamab.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 9

Exclusion criteria:
1. Secondary forms of IgAN, indicated by the presence of any other systemic disease potentially leading to IgA deposits (e.g. Lupus nephritis, Schönlein-Henoch purpura, ankylosing spondylitis, dermatitis herpetiformis, chronic liver disease, inflammatory bowel disease, celiac disease).
2. Severe renal impairment as defined by estimated GFR < 30 mL/min (using chronic kidney
disease-epidemiology collaboration [CKD-EPI] formula) or the need for dialysis or renal transplant.
3. Rapidly progressive variant of IgAN, defined as eGFR loss by more than 30% per 3 months and not explained by changes in renin angiotensin system (RAS) blockade.
4. Minimal change variant of IgAN.
5. Concomitant other progressive glomerulonephritis or non-immunologic glomerular disease such as diabetic nephropathy.
6. Systemic immunosuppression (e.g. mycophenolate mofetil [MMF], cyclophosphamide, biologics like rituximab [RTX]), in particular corticosteroid therapy exceeding 20 mg/day prednisone-equivalent for more than 7 consecutive days within 180 days prior to signing ICF.
7. Any previous treatment with an anti-CD38 antibody.
8. Body mass index (BMI) > 35 kg/m^2.
9. Hemoglobin < 90 g/L.
10. Thrombocytopenia: Platelets < 100.0 x 10^9/L.
11. Neutropenia: Neutrophils < 1.5 x 10^9/L.
12. Leukopenia: Leukocytes < 3.0 x 10^9/L.
13. Diabetes mellitus type 1.
14. Diabetes mellitus type 2: Patients with type 2 diabetes mellitus may only enter the clinical trial if a kidney biopsy performed within 6 months prior to signing ICF shows IgAN without evidence of diabetic nephropathy and their disease is controlled, such as:
a. Glycated hemoglobin (HbA1c) < 8.0% or < 64 mmoL/mol.
b. No diabetic retinopathy known.
c. No peripheral neuropathy known.
15. Significant uncontrolled cardiovascular disease (including arterial or venous thrombotic or embolic events) or cardiac insufficiency (New York Heart Association [NYHA] class IV) as judged by the investigator.
16. Clinically significant findings on a 12-lead electrocardiogram (ECG) as determined by the investigator at screening.
17. History of significant cerebrovascular disease or sensory or motor neuropathy of toxicity = grade 3.
18. Aspartate aminotransferase or alanine aminotransferase >1.5 x ULN, alkaline phosphatase >3.0 x ULN.
19. Known or suspected hypersensitivity to Felzartamab and its excipients (L-histidine, sucrose, polysorbate 20).
20. Serologic markers positive for HIV or history of HIV, hepatitis C (patients with positive anti-hepatitis C virus [anti-HCV] antibody but negative HCV RNA polymerase chain reaction [PCR] can enroll) or active or latent hepatitis B (patients with positive hepatitis B surface antigen [HBsAg] are excluded). For patients with positive hepatitis B core antibody [anti-HBc], hepatitis B virus (HBV) DNA test by PCR must be non-detectable to enroll).
21. Any malignancy within 5 years prior to screening start, with the exception of adequately treated in situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or other non-melanomatous skin cancer.
22. Treatment within 5 terminal half-lives (if known) or within the last 30 days prior to Visit 2, whatever is longer) with investigational drugs.
23. Any active infection (viral, fungal, bacterial) requiring systemic therapy.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

IgA Nephropathy (IgAN)
MedDRA version: 20.0 Level: PT Classification code 10021263 Term: IgA nephropathy System Organ Class: 10038359 - Renal and urinary disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: Felzartamab
Product Code: MOR202
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Felzartamab
CAS Number: 2197112-39-1
Current Sponsor code: MOR202
Other descriptive name: MOR03087
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 65-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 9 months

Main Objective: To assess the efficacy of Felzartamab compared to placebo in patients with IgAN based on the change in urine protein to creatinine ratio (UPCR) at 9 months.

Primary end point(s): Relative change in UPCR in 24h urine compared to the reference proteinuria value in the Felzartamab dose groups vs. placebo.

Secondary Objective: To assess the relationship between exposure, safety, and efficacy in each of the three dose groups vs. placebo to support a decision for a dose in further trials
To assess the efficacy of Felzartamab compared to placebo in patients with IgAN based on the following:
- Change in UPCR at 3, 6, 12, 18 and 24 months
- Complete response (CR) at 3, 6, 9, 12, 18 and 24 months
- Proportion of patients with response at 3, 6, 9, 12, 18 and 24 months
- Albumin-creatinine ratio (ACR) at 6, 9, 12, 18 and 24 months
- Duration of response
- Time to response
To assess the renal function of Felzartamab compared to placebo in patients with IgAN.
To assess the safety of Felzartamab in patients with IgAN.
To assess the pharmacokinetic (PK) profile of Felzartamab in patients with IgAN.
To investigate the potential immunogenicity of Felzartamab in patients with IgAN

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: The primary analysis will be performed after all randomized patients in Part I of the study have completed their 9 month-visit or discontinued the trial earlier. The final analysis of all endpoints will be performed after all randomized patients (both Part I and Part II) have completed their last visit, or discontinued the trial earlier.
The secondary endpoints will be assessed at 3, 6, 9, 12, 18, 24 months as defined per each in study protocol.

Secondary end point(s): Integrative analysis of several endpoints.
Relative change in UPCR in 24h urine compared to the reference proteinuria value in each Felzartamab dose group vs. placebo.
Complete response in each Felzartamab dose group vs. placebo.
Proportion of patients with response in each Felzartamab dose group vs. placebo.
Albumin-creatinine ratio from 24 h urine in each Felzartamab dose group vs. placebo.
Duration of response in each Felzartamab dose group vs. placebo.
Time to response in each Felzartamab dose group vs. placebo.
Renal function (determined by estimated glomerular filtration rate [eGFR] over time) in each Felzartamab dose group vs. placebo.
Frequency, incidence, seriousness, relatedness, and severity of treatment-emergent adverse events (TEAEs) across all treatment groups.
Serum concentrations of Felzartamab over time in each Felzartamab dose group.
Formation of anti-drug antibodies (ADAs) over time in all groups

Secondary ID(s)

142840

2020-005054-19-CZ

MOR202C206

Source(s) of Monetary Support

Human Immunology Biosciences, Inc

Ethics review

Status: Approved
Approval date: 16/08/2021
Contact: