QRK309

Quark Pharmaceuticals, Inc.

7999 Gateway Boulevard, Suite 310, Newark, United States, 94560

Clinical Operations, Quark Pharmaceuticals, Inc., dcafaro@quarkpharma.com

Clinical Operations, Quark Pharmaceuticals, Inc., dcafaro@quarkpharma.com

No

No

No

Final

23 Jan 2021

Yes

23 Jan 2021

Yes

30 Mar 2021

Yes

• Primary objective: To assess the efficacy of a single intravenous (IV) infusion of QPI-1002 in preventing Major Adverse Kidney Events (MAKE) in subjects at high risk for acute kidney injury (AKI) following cardiac surgery. • Secondary objectives: To assess the safety and tolerability of an IV infusion of QPI-1002 in comparison to placebo when administered to subjects at high risk for AKI following cardiac surgery.

The trial was completed according to the International Conference on Harmonization (ICH) Guidelines for Good Clinical Practice. Compliance with this standard provides public assurance that the rights, safety, and well-being of trial subjects are protected, consistent with the principles that have their origin in the Declaration of Helsinki.

25 May 2018

No

Yes

Australia: 49

Canada: 254

New Zealand: 36

United States: 311

Spain: 86

Austria: 6

Belgium: 8

Czechia: 43

France: 17

Germany: 233

1043

393

0

0

0

0

0

0

173

852

18

Overall trial (overall period)

Randomised - controlled

Yes

QPI-1002

Teprasiran

Solution for injection

Intravenous bolus use

QPI-1002 injection is supplied at 25 mg/mL in a preservative-free, sterile solution compounded in phosphate-buffered-saline. Each 10 mL vial contains 250 mg of QPI-1002. There is no reconstitution or dilution of QPI-1002 injection. The calculated dose of investigational product to be administered is determined using the subject's weight (kg) obtained at the Baseline visit. The injection is administered directly into the most proximal port of an available central venous line or through an available peripheral line (if no central line can be accessed), using standard IV push technique, including flushing the line prior to and after administration. The solution will be administered via IV bolus, at a dose of 10 mg/kg, approximately 4 h ± 30 min after discontinuation of CPB. In case of non-CPB surgery (subjects < 45 years old), study drug will be administered approximately 4 h ± 30 min after the last coronary bypass and completion of anastomosis and achievement of hemostasis.

Placebo

Solution for injection

Intravenous bolus use

Placebo is commercially available isotonic saline for injection matched for volume. The injection is administered directly into the most proximal port of an available central venous line or through an available peripheral line (if no central line can be accessed), using standard IV push technique, including flushing the line prior to and after administration. The solution will be administered via IV bolus, at a dose of 10 mg/kg, approximately 4 hours ± 30 minutes after discontinuation of CPB. In case of non-CPB surgery (subjects 18 to < 45 years old), study drug will be administered approximately 4 hours ± 30 minutes after the last coronary bypass and completion of anastomosis and achievement of hemostasis.

QPI-1002

Placebo

ITT

The ITT population is defined as all subjects who are randomized, regardless of the treatment the subject actually received. The ITT population was used for the assessment of the primary endpoint in subjects aged 45 years and above.

QPI-1002

Placebo

ITT

The ITT population is defined as all subjects who are randomized, regardless of the treatment the subject actually received. The ITT population was used for the assessment of the primary endpoint in subjects aged 45 years and above.

The primary efficacy endpoint was defined as the proportion of subjects 45 years old and above who develop any of the components of MAKE90, defined as either death through day 90, initiation of renal replacement therapy (RRT) through day 90, or a ≥ 25% reduction in eGFR at the Day 90 visit. For the primary analysis, eGFR was to be based on serum cystatin C (eGFRcys). Estimated GFR based on serum creatinine (eGFRcreat) was to be used in a sensitivity analysis.

Primary

Day 90

The analysis of the primary endpoint was conducted on the intention-to-treat (ITT) population in subjects aged 45 years and above. The ITT population was analyzed as randomized, regardless of the treatment the subject actually received. MAKE90 is defined as experiencing any one of these components: Death through Study Day 90, Initiation of Renal Replacement Therapy (RRT) through Day Study 90, or a >=25% reduction in eGFRScysC at the Day 90 Visit from Baseline.

QPI-1002 v Placebo

1039

Pre-specified

0.93

2-sided

All adverse events were collected through Day 30. Serious adverse events (SAEs)were collected through 90 days post study drug administration. Renal function, subject survival and malignancy status were assessed at Day 365.

Safety assessments (AEs and SAEs) were reported with their severity and relationship to study drug. Vital signs and routine labs (haematology and chemistry panel) were also collected. Safety analyses were conducted in the as-treated population, defined as all subjects randomized and dosed (QPI-1002 or placebo) regardless of age.

23

QPI-1002

Placebo