Open Label Clinical Trial to assess Safety and Efficacy of MOR202 in Membranous Nephropathy

• Register: EUCTR
• Last refreshed on: 8 August 2022
• Main ID: EUCTR2019-000780-24-PL
• Date of registration: 14/09/2020
• Prospective Registration: Yes
• Primary sponsor: MorphoSys AG
• Public title: Open Label Clinical Trial to assess Safety and Efficacy of MOR202 in Membranous Nephropathy
• Scientific title: A Phase Ib/IIa, Open-Label, Multicenter Clinical Trial to Assess Safety and Efficacy of the Human Anti-CD38 Antibody MOR202 in anti-PLA2R antibody positive Membranous Nephropathy (aMN) - M-PLACE
• Date of first enrolment: 07/01/2021
• Target sample size: 30
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-000780-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, European Union, France, Italy, Korea, Republic of, Netherlands, Poland, Spain, United States

Contacts

• Name: Global Clinical Program Head
• Affiliation: MorphoSys AG

• Name: Global Clinical Program Head
• Affiliation: MorphoSys AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. =18 to =80 years, at date of signing informed consent form (ICF).
2. Urine protein to creatinine ratio (UPCR) of = 3.0000 g/g OR proteinuria = 3.500g/24 h from 24-h urine at screening.
3. Anti-PLA2R antibody positive MN in need for IST according to investigator's judgement. The diagnosis of MN should be histologically documented with a diagnostic biopsy; for this purpose, a biopsy at screening or an archival biopsy acquired within 5 years prior screening is acceptable.
4.Estimated glomerular filtration rate (eGFR) = 50 mL/min/1.73m². Alternatively eGFR =30 and <50 mL/min/1.73m² and interstitial fibrosis and tubular atrophy (IFTA) score < 25% in a renal biopsy obtained within the last 6 months prior to start of screening (if not available, a biopsy should be performed at screening to obtain the IFTA assessment).
5. Not in spontaneous remission despite proper treatment with ACEIs, ARBs (sufficient dose and treatment duration) as per clinical practice and guidelines. If the PI determines that a subject is intolerant to an ACEI or ARB, the reason must be documented and approval obtained from the Medical Monitor prior to enrolment.
6. Systolic BP = 150 mmHg and diastolic BP = 100 mmHg after a period of 5 minutes rest.
7. Subject vaccinated against Pneumococcus within the last 5 years prior to date of signing ICF (subjects may be vaccinated during screening to meet this criterion during screening; interval to first dose of MOR202 must be at least 14 days [MSD SmPC]).
8. Cohort 1 comprises newly or relapsed subjects: Serum anti-PLA2R antibodies =50.0 RU/ml determined by Euroimmun ELISA at central laboratory.
9. Cohort 2 comprises therapy refractory subjects:
a. subject did not achieve immunological remission after prior IST(s) as documented by the investigator AND
b. subject is without promising standard therapeutic options as documented by the investigator(i.e. investigator expects efficacy or safety issues with remaining IST options AND
c. serum anti-PLA2R antibodies =20RU/mL measured at screening by the Euroimmun ELISA at central laboratory
10. Female of non-childbearing potential fulfilling one of the criteria:
a. post-menopausal: after 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms)
b. surgically sterile: tubal ligation at least 6 weeks before taking trial treatment, hysterectomy, or bilateral oophorectomy
c. genetically sterile: e. g. Turner syndrome, uterine agenesis.
11. Sexually active females of reproductive potential should use one of the following contraception options until 3 months after the last dose of MOR202:
a. One method of contraception that has a typical use failure rate of <1% (i.e., less than 1 pregnancy expected per 100 women), which would include
sterilization surgery for women, sterilization implant for women, sterilization surgery for men, Copper intra-uterine device (IUD), IUD with progestin, or implantable rod
b. A hormonal method of contraception (i.e., shot/injection, oral contraceptive, contraceptive patch, vaginal contraceptive ring, having typical use failure rate = 9%) plus a barrier method (i.e., diaphragm with spermicide, sponge with spermicide, cervical cap with spermicide, male condom, female condom, spermicide alone).
Note: France will only enroll patients in Cohort 2.
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
Exclusion criteria:
1.Hemoglobin < 80 g/L
2.Thrombocytopenia: Platelets < 100.0 × 109/L
3.Neutropenia: Neutrophils < 1.5 × 109/L
4.Leukopenia: Leukocytes < 3.0 × 109/L
5.Hypogammaglobulinemia defined as serum immunoglobulin = 4.0 g/L
6.B-cells < 5 × 106/L.
7.Secondary cause of MN (e.g. SLE, medications, malignancies) as determined by the investigator.
8.Concomitant renal disease other than MN (e.g., diabetic renal disease, lupus nephritis, IgA nephropathy).
9.Diabetes mellitus type 1.
10.Diabetes mellitus type 2: Subjects with type 2 diabetes mellitus may only enter the clinical trial if a kidney biopsy performed within 6 months prior to screening shows MN without evidence of diabetic nephropathy and their disease is controlled, such as:
•Hba1c < 8.0 % or 64 mmol/mol
•No diabetic retinopathy known
•No peripheral neuropathy known
11.Previous treatment with an anti-CD38 antibody.
12.Subject received treatment with:
a.Mycophenolate mofetil (MMF) or high dose corticosteroids (> 20 mg prednisone/day), within 30 days prior to screening OR
b.Alkylating agents (e.g. cyclophosphamide [CYC]) or CNIs (e.g. tacrolimus, cyclosporine A [CSA]) within 90 days OR
c.Biologic drugs including RTX within 180 days
d.Any other oral/parenteral IST within 180 days.
13.Significant uncontrolled cardiovascular disease or cardiac insufficiency (New York Heart Association [NYHA] class IV) as judged by the investigator.
14.Clinically relevant findings on a 12-lead ECG as determined by the investigator at screening.
15.History of significant cerebrovascular disease or sensory or motor neuropathy of toxicity = grade 3.
16.Total bilirubin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 1.5 × ULN, alkaline phosphatase (ALP) > 2.0×ULN.
17.Treatment within five terminal half-lives (if known) or within the last 30 days prior to baseline (whatever is longer) with investigational drugs.
18.Known or suspected hypersensitivity to MOR202 and its excipients (L-histidine, sucrose, polysorbate 20).
19.Serologic or virologic markers positive for HIV, hepatitis C (subjects with positive anti hepatitis C virus [anti-HCV] antibody but negative HCV RNA polymerase chain reaction [PCR] may enroll) or active or latent hepatitis B (subjects with positive hepatitis B surface antigen [HBsAg] are excluded, subjects with isolated positive hepatitis B core antibody [anti-HBc] but non-detectable hepatitis B virus (HBV) DNA by PCR may be enrolled).
20.For any other pre-existing symptoms and impairments of health classified or any residual toxicity from prior therapy = grade 3 (NCI-CTCAE, see Section 3.2): these subjects may be included upon confirmation by the medical department of the sponsor.
21.Pregnancy or breast feeding.
22.Any active infection (viral, fungal, bacterial) requiring systemic therapy.
23.Any malignancy within 5 years prior to date of screening, with the exception of adequately treated in situ carcinoma of the cervix, uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer.


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

Health Condition(s) or Problem(s) studied

Primary (anti-PLA2R antibody positive) Membranous Nephropathy
MedDRA version: 21.1 Level: LLT Classification code 10027170 Term: Membranous nephropathy System Organ Class: 100000004857

Therapeutic area: Body processes [G] - Immune system processes [G12]

Intervention(s)

Product Name: MOR202
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-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Throughout the study

Secondary Objective: To assess the effect of MOR202 on serum anti-PLA2R antibodies in subjects with aMN
To assess immunogenicity of MOR202 (anti-MOR202 antibody formation)
To assess the pharmacokinetic (PK) profile of MOR202
To assess the safety in subjects with aMN after MOR202 treatment and during follow-up phase

Main Objective: To assess the safety and tolerability of MOR202 treatment in subjects with anti-PLA2R antibody positive membranous nephropathy (aMN)

Primary end point(s): Incidence and severity of treatment-emergent adverse events (TEAE)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Throughout the study

Secondary end point(s): KEY SECONDARY ENDPOINT: Best Immunological Response: rate of stringent immunological complete response (sICR), immunological complete response (ICR) and immunological partial response (IPR) based on reduction of serum anti-PLA2R antibody titer
SECONDARY ENDPOINTS:
1. Number and antibody titers of subjects tested positive for anti-MOR202 antibodies
2. MOR202 serum concentrations after multiple i.v. administrations
3. Incidence and severity of AEs in the follow-up phase

Secondary ID(s)

2019-000780-24-NL

142840

MOR202C103

Source(s) of Monetary Support

MorphoSys AG

Ethics review

Status: Approved
Approval date: 08/09/2020
Contact: