A Phase II Study with Sevuparin in Subjects with Chronic Kidney Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Modus Therapeutics AB

Participant type

Patients, Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

28 Nov 2024 → ongoing

Decision date (initial)

2024-11-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Modus Therapeutics AB

External identifiers

EU CT number

2024-513864-24-00

WHO UTN

U1111-1310-6826

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Pharmacodynamic

Part 1: To develop a nomogram to correlate glomerular filtration rate (GFR) to pharmacokinetic (PK) parameters to allow individualised dosing in Part 2 based on GFR.
Part 2: To evaluate the change from baseline of key haematological and biochemical parameters related to anaemia and kidney function, following multiple SC doses of sevuparin in subjects with CKD.

Secondary objectives 4

1. Part 1: To evaluate the pharmacodynamics (PD) of sevuparin by determining the change from baseline of serum hepcidin levels following a single SC dose of sevuparin in subjects with CKD.
2. Part 1: To evaluate the safety and tolerability of a single SC dose of sevuparin in healthy subjects and subjects with CKD.
3. Part 2: To evaluate the pharmacodynamics (PD) of sevuparin by determining the change from baseline of serum hepcidin levels following multiple SC doses of sevuparin in subjects with CKD.
4. Part 2: To evaluate the change from baseline of key haematological and biochemical parameters related to anaemia and kidney function, following multiple SC doses of sevuparin in subjects with CKD.

Conditions and MedDRA coding

Chronic kidney disease

Study design 1 period

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Both healthy volunteers and patients: Signed informed consent prior to any study specific procedure.
2. For healthy volunteers only: Healthy male and female subjects aged between 18 and 55 years (inclusive) at Screening.
3. For both healthy volunteers and patients: Ability to communicate well with the investigator, in a language understandable to the subject, and to understand and comply with the requirements of the study.
4. For healthy volunteers only: No clinically relevant findings on the physical examination at Screening.
5. Both healthy volunteers and patients: Body mass index (BMI) of 18.0 to 32.0 kg/m2 (inclusive) at Screening and body weight of at least 50 kg.
6. For both healthy volunteers and patients: Contraception measure as per the CTFG guidance.
7. For patients only: Subjects will be males and females of any racial or ethnic origin aged 18-75.
8. For patients only: Moderate renal impairment with CKD Stage 3 (eGFR 30-44 mL/min/1.73m2) or severe renal impairment (Stage 4, eGFR 15-29 mL/min/1.73m2 or Stage 5, eGFR 15-29 mL/min/1.73m2 or requiring haemodialysis or peritoneal dialysis).
9. For patients only: Stable drug regimen defined as not starting a new drug or changing dosage within seven days or five half-lives before Day 1 of the study.

Exclusion criteria 13

1. For both healthy volunteers and patients: Pregnant or lactating women.
2. For healthy volunteers only: No clinically relevant findings in clinical laboratory tests (haematology including reticulocytes, clinical chemistry, coagulation, urinalysis) at Screening.
3. For healthy volunteers only: Positive results from urine drug screen, urine cotinine, and urine alcohol tests at Screening and pre-dose on Day 1. Positive screening test for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, or anti-HIV 1 and 2 antibodies.
4. For healthy volunteers only: Serum or plasma potassium <3.5 or >5.2 mEq/L at screening. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >1.5 × ULN or total bilirubin >1.5 × ULN at screening. Gilbert’s syndrome. Any repeated laboratory abnormality considered by Investigator to be clinically significant.
5. For healthy colunteers only: Mean systolic blood pressure <90 mmHg or >140 mmHg, after at least 5 minutes rest in a supine position at Screening or pre-dose at Day 1. Clinically significant ECG abnormality, as judged by the Investigator at Screening. In addition, any subject any one of the following ECG abnormalities (based on the average of the triplicate results) will be excluded: i. Uncorrected QT-interval >500 ms. ii. QTcF >470 ms. iii. QRS interval >130 ms. iv. PR interval >220 ms. eGFR by CKD-EPI >80 mL/min/m2.
6. For healthy volunteers only: Clinically relevant history or presence of rhythm disorders (e.g., sinoatrial heart block, second- or third-degree atrioventricular block, long QT syndrome, symptomatic bradycardia, atrial flutter, or atrial fibrillation), clinically relevant history of hypokalaemia, congestive heart failure or structural heart disease.
7. For healthy volunteers only: Clinical evidence of significant or unstable medical illness including neurological, haematological (including von Willebrand disease and heparin-induced thrombocytopenia, HIT), hepatic, pulmonary, metabolic, gastrointestinal, renal, psychiatric, endocrine or infectious diseases or malignancies. Subjects who have had splenectomy.
8. For healthy volunteers only: History or clinical evidence of any disease and/or existence of any surgical or medical condition, which, in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the study treatment. Acute, ongoing, recurrent, or chronic systemic disease that may to interfere with the evaluation of the study results.
9. For both healthy volunteers and patients: Any relevant condition, behaviour, laboratory value or concomitant medication which, in the opinion of the investigator, makes the subject unsuitable for entry into the study.
10. For patients only: Renal allograft recipients. Urinary incontinence without catheterization. Subjects with significant hepatic, cardiac, or pulmonary disease or subjects who are clinically nephrotic.
11. For patients only: Screening AST, ALT, GGT ≥2.0 × upper limit of normal; international normalized ratio (INR) >1.4; platelet count <75,000/μL. Total bilirubin level 1.5 × ULN; subjects with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible provided the direct bilirubin level is not greater than 0.5 mg/dL. Supine blood pressure and pulse >160/90 mmHg and 100 bpm, respectively, or <90/45 mmHg and 50 bpm, respectively, confirmed upon triplicate measurements.
12. For patients only: Current use of coumarins including warfarin, anti-coagulation factor concentrates, chronic/subchronic use of unfractionated heparin or low molecular weight heparins (LMWH) unless in conjunction with haemodialysis treatment. Use of diuretics, renin-angiotensin system (RAS) blockers, angiotensin-converting-enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) unless at a stable dose for at least 3 months prior to enrolment.
13. For both healthy volunteers and patients: Clinically significant history of any drug sensitivity, drug allergy, heparin-induced thrombocytopenia or food allergy, as determined by the Investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part 1: Pharmacokinetic parameters including observed maximal plasma concentration (Cmax), time of maximum observed plasma concentration (tmax), AUC from time zero to the last quantifiable concentration (AUC0-tlast), AUC from time zero to infinity (AUC0-∞), terminal elimination half-life (t1/2λz) and renal clearance (CLR).
2. Part 2: Assessment of safety parameters including type and severity of adverse events (AEs), electrocardiograms (ECGs), vital signs, clinical laboratory evaluations (serum biochemistry, haematology including reticulocytes and coagulation parameters), urinalysis (dipstick) and physical examinations.

Secondary endpoints 2

1. Part 1: Assessment of the change from baseline in serum hepcidin. • Assessment of safety parameters including type and severity of AEs, ECGs, vital signs, physical examinations, and clinical laboratory evaluations i.e., serum biochemistry, haematology (including reticulocytes and coagulation parameters) and urinalysis (dipstick).
2. Part 2: Assessment of the change from baseline in serum hepcidin. Assessment of the change from baseline in haemoglobin (Hb), haematocrit (b-Ht), and reticulocyte haemoglobin (b-RetHb) in blood and serum creatinine (s-Crea). Assessment of PK parameters including Cmax, tmax, AUC0-tlast, AUC0-∞, t1/2λz, plasma accumulation ratio for Cmax and AUC, time to steady state.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Modus Therapeutics AB

Sponsor organisation

Modus Therapeutics AB

Address

Stockholms Domkyrkofors, Olof Palmes Gata 29 IV Olof Palmes Gata 29 IV

City

Stockholm

Postcode

111 22

Country

Sweden

Scientific contact point

Organisation

Modus Therapeutics AB

Contact name

John Öhd

Public contact point

Organisation

Modus Therapeutics AB

Contact name

John Öhd

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications