A phase 2b dose finding study of RMC-035 in participants undergoing open-chest cardiac surgery

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Guard Therapeutics International AB (publ)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12], Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

24 Sep 2024 → 12 Sep 2025

Decision date (initial)

2024-08-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Guard Therapeutics International AB

External identifiers

EU CT number

2024-510658-28-00

WHO UTN

U1111-1303-6704

ClinicalTrials.gov

NCT06475274

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate efficacy of RMC-035 vs placebo on renal function at Day 90 and to identify the optimal dose of RMC-035 for protection of long-term renal function in patients undergoing cardiac surgery who are at high risk of kidney injury.

Secondary objectives 2

1. To assess efficacy of RMC-035 (pooled low and high doses, and by each dose level) vs placebo on MAKE at Day 90
2. To evaluate efficacy of each dose level of RMC-035 (low and high doses, respectively) vs placebo on renal function at Day 90

Conditions and MedDRA coding

Loss of renal function following cardiac surgery

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. Age is ≥18 and <85 years at the time of signing the informed consent.
2. 2. eGFR is ≥30 ml/min/1.73m2 (at screening) using the CKD-EPI 2021 equation with SCr.
3. 3. Scheduled for non-emergent surgery of any or several of the following types with use of CPB: a. CABG surgery b. Valve surgery (single or multiple valves) c. Ascending aorta aneurysm surgery
4. 4. Risk factors for kidney injury are present (at screening) as specified below: a. eGFR is <60 mL/min/1.73m2 b. If eGFR is ≥60 mL/min/1.73m2 i. A combined surgery is scheduled AND at least one risk factor for kidney injury from list (1) to (8) below is present. ii. One type of surgery is scheduled AND at least two risk factors for kidney injury from list (1) to (8) below are present. Risk factors for AKI: (1) Documented history of LVEF <35% at any time during the 3-month period before or at the time of screening as assessed by either echocardiography, cardiac MRI or nuclear scan. (2) Repeat surgery/history of previous open chest cavity cardiac surgery with or without CPB. (3) Confirmed diagnosis of T2DM at least 3 months prior to screening AND ongoing treatment with an approved anti-diabetic drug. (4) Age ≥70 years at the time of screening. (5) Documented history of NYHA class II or higher at any time during the 3-month period before or at the time of screening (6) Documented history of AKI as per KDIGO criteria longer than 3 months before date of screening, independent of the etiology of AKI. (7) Documented history of anemia with hemoglobin ≤11 g/dL at any time during the 3-month period before or at the time of screening. (8) Documented history of albuminuria, defined as urine albumin-to-creatinine ratio (UACR) >100 mg/g in a spot urine sample or >100 mg/24 hour in a 24-hour urine collection at any time during the 3-month period before or at the time of screening.
5. 5. Female Participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: - Is a WONCBP as defined in the protocol. - Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of < 1% per year), with low user dependency, as described in the protocol. A female participant is eligible to participate if she agrees not to donate ova during the study intervention period and for at least 7 days after the last dose of study intervention. A WOCBP must have a negative highly sensitive pregnancy test (serum) within 48 hours before the first dose of study intervention. Additional requirements for pregnancy testing during and after study intervention are located in the protocol. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
6. 6. Male Participants: Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 7 days after the last dose of study intervention: a. Refrain from donating fresh unwashed semen. b. And either (i) or (ii) below: i. Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent. ii. Must agree to use contraception/barrier as detailed below: - Agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant. - Agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person.
7. 7. Capable of giving signed informed consent as described in the protocol which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
8. 8. Participant agrees not to participate in another interventional study from the time of signing the informed consent until the EOS visit.

Exclusion criteria 19

1. 1. Any medical condition that in the opinion of the investigator makes the participant unsuitable for study participation. This includes participants unable to give their informed consent.
2. 2. Scheduled for emergent surgeries (eg, aortic dissection).
3. 3. Scheduled for CABG and/or valve surgery and/or ascending aorta aneurysm surgery combined with additional non-emergent cardiac surgeries (eg, congenital heart defects). Scheduled additional left atrial appendage closure surgery or maze surgery is not an exclusion criterion.
4. 4. Scheduled to undergo TAVI or TAVR, or off-pump surgeries or LVAD implantation.
5. 5. Experiences a cardiogenic shock or hemodynamic instability which require inotropes or vasopressors or other mechanical devices such as IABP within 24 hours prior to surgery.
6. 6. Requires any of the following within one week prior to surgery: defibrillator or permanent pacemaker, mechanical ventilation, IABP, LVAD, other forms of MCS.
7. 7. Diagnosed with AKI (as defined by KDIGO criteria) within 3 months prior to surgery.
8. 8. Requires cardiopulmonary resuscitation within 14 days prior to cardiac surgery.
9. 9. Ongoing sepsis (as defined in the protocol) within the past 2 weeks or, in the opinion of the investigator, an untreated diagnosed clinically significant infection (viral or bacterial) prior to or at screening and before randomization.
10. 10. ALT or AST ≥3.0 x ULN.
11. 11. Total bilirubin ≥2.0 xULN (Participants with Gilbert’s syndrome can be included with total bilirubin ≥1.5 x ULN as long as direct bilirubin is < 1.5 x ULN).
12. 12. History of solid organ transplantation.
13. 13. History of Renal Replacement Therapy.
14. 14. Severe allergic asthma defined as confirmed diagnosis of asthma poorly controlled while receiving high-dose inhaled corticosteroid treatment, or with requirement of a high level of treatment to maintain control.
15. 15. Chronic immunosuppressive treatment that may have an impact on kidney function as assessed by the medical monitor.
16. 16. Ongoing chemotherapy or radiation therapy for malignancy that may have an impact on kidney function as assessed by the medical monitor.
17. 17. Current enrolment or past participation within the last 90 days (or within 5 half-lives of an investigational study treatment, whichever is longer) before signing of consent in any other clinical study involving an investigational study treatment.
18. 18. Has previously received RMC-035.
19. 19. Hypersensitivity to any of the study interventions, or components thereof including excipients, or drug or other allergy that, in the opinion of the investigator, contraindicates participation in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in eGFR based on SCr at Day 90 (pooled low and high dose levels)

Secondary endpoints 2

1. Occurrence of MAKE (and each MAKE component) at Day 90 (pooled low and high doses, and by each dose level)
2. Change from Baseline in eGFR based on SCr at Day 90 (low and high doses, respectively)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Guard Therapeutics International AB (publ)

Sponsor organisation

Guard Therapeutics International AB (publ)

Address

P. O. Box 5216

City

Stockholm

Postcode

102 45

Country

Sweden

Scientific contact point

Organisation

Guard Therapeutics International AB (publ)

Contact name

Sara Thuresson

Public contact point

Organisation

Guard Therapeutics International AB (publ)

Contact name

Sara Thuresson

Third parties 6

Locations

3 EU/EEA countries · 14 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

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