Primary Efficacy Endpoint
The CRUISE-1 study successfully met its pre-defined primary efficacy endpoint, which was a change in hemoglobin from Baseline to End-of-Treatment between the SFP and placebo groups. The mean difference between SFP and placebo was 3.6 g/L (95% CI 0.8, 6.3) in favor of SFP, and was statistically significant (p=0.011).
At baseline the two groups had similar hemoglobin levels (109.6 g/L SFP and 109.0 g/L placebo). The mean adjusted change from baseline hemoglobin to the end of the randomized treatment period in the SFP group was 0.6 g/L (95% CI -1.7, 2.8). In the placebo group there was a statistically significant decline of -3.0 g/L (95% CI -5.3, -0.8).
Key Secondary Endpoints
The key secondary endpoints at End-of-Treatment showed statistically significant differences between the SFP and placebo groups, including the pre-dialysis reticulocyte hemoglobin (CHr) and serum ferritin. CHr, an early index and the best marker of iron-delivery to the bone marrow, was maintained at baseline levels in the SFP group during the randomized treatment, compared to a significant decrease in the placebo group. At End-of-Treatment, the difference between groups was a statistically significant 2.1% difference in favor of SFP (p < 0.001). Serum ferritin, a marker of tissue iron stores, declined by 14.7% from baseline in the SFP arm while the placebo group ferritin level declined by 28.2%. The difference between groups was statistically significant (p < 0.001). These results indicate that hemodialysate containing 2 µM SFP iron delivers sufficient iron to maintain erythropoiesis and does not lead to tissue iron overload.
Overall the adverse events reported were those that are expected in the chronic hemodialysis population. There were no differences in frequency or severity between the SFP and placebo groups with respect to AEs or serious adverse events. Importantly, the incidence of intradialytic hypotension, infections, and cardiac events in the SFP group was similar to or less than that observed in the placebo group. There were no events of anaphylaxis or hypersensitivity reported with dialysis administrations of SFP.
|Adverse Events||SFP N=149
|Procedural (Intradialytic) Hypotension||43||(28.9)||41||(27.2)|
|Hemodialysis induced Symptom||7||(4.7)||5||(3.3)|
|AVF Hemorrhage or Thrombosis||8||(5.4)||6||(4.0)|
|AVG complication or Thrombosis||6||(4.0)||4||(3.3)|
The CRUISE-1 study was a single-blind, placebo controlled, parallel group study comparing SFP (2µM [110 µg iron/L] delivered via hemodialysate concentrate) to placebo (standard hemodialysate concentrate). Adult patients with chronic kidney disease on regular hemodialysis, who were receiving stable doses of erythropoiesis stimulating agents (ESAs) and who were iron replete (as measured by serum transferrin saturation between 15 % to 40% and serum ferritin between 200 to 800 µg/L), were eligible for randomization. Patients who met the inclusion criteria entered a run-in period of 1 to 4 weeks. During the run-in, no study drug was administered, and no changes in the dose or route of administration of ESA were allowed. IV and oral iron products were not allowed from run-in through the end of randomized treatment.
Patients who continued to meet inclusion criteria during the run-in period were randomized 1:1 to receive either SFP via dialysate or placebo (standard dialysate) in a blinded manner for up to 48 weeks. Patients received the designated study drug at each dialysis session during the randomized treatment period. Hemoglobin, the measurement for the primary endpoint, was assessed weekly, along with iron parameters every two weeks. Randomized patients could remain in the study for up to 48 weeks
Over the course of the study patients were not permitted to have their ESA dose adjusted from baseline dose, and were not permitted IV or oral iron. The study design incorporated a pre-defined protocol to address safety criteria and removed patients prior to 48 weeks who met any of the following removal criteria: 1) a need to change ESA dose for low or high ( < 90 or > 120 g/L) hemoglobin values, 2) rapidly rising hemoglobin defined as > 115 g/L and an increase of 10 g/L over 4 weeks, or 3) serum ferritin < 100 µg/
The primary study population was the modified Intent-to-Treat (mITT) population, defined as all patients who were randomized, and received at least one dose of study drug, and had at least one post-baseline hemoglobin value during the randomized treatment period.
The primary outcome measure for this study was the mean change in hemoglobin level from baseline to the End-of-Treatment. End-of-Treatment was defined as the average of the hemoglobin levels during the last 1/6th of the randomized treatment period of each patient. A minimum of at least two on-study hemoglobin values were necessary for inclusion in the analysis. The primary outcome statistic was provided by an analysis of covariance (ANCOVA) for the change from baseline hemoglobin between treatment groups, using baseline hemoglobin value as a covariate.
Secondary endpoints included the changes from baseline in pre-dialysis reticulocyte hemoglobin (CHr), ferritin and serum iron parameters. Safety endpoints included all treatment emergent adverse events (TEAEs), serious adverse events (TESAEs), intradialytic hypotension, cardiac events and anaphylactic/hypersensitivity events.
At baseline, the two treatment groups were well balanced with respect to age (mean 58 years), gender (32% female, 68% male), race (55% white, 32% black and 13% other) and ethnicity. There were 152 patients randomized to the SFP treatment arm and 153 patients were randomly assigned to receive placebo. The mean duration of participation in the randomized treatment period was approximately 6 months (23 weeks). As the pre-defined safety criteria protocol specified, there were a number of patients removed prior to end of study for reasons of safety/anemia management. Due to pre-defined reasons of safety/anemia management (see pre-defined safety criteria under Study Design, above), 69 patients were removed in the SFP arm and 83 were removed in placebo. Due to anemia related protocol violations (IV iron or ESA given), 19 patients were removed from the study in the SFP arm and 22 in placebo. 1 patient was removed in the SFP arm and 7 patients in placebo due to blood transfusions. Other reasons for early termination were balanced between the groups.
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SFP is a unique iron compound that is delivered to the hemodialysis patient via dialysate, replacing the 5-7 mg of iron lost during a dialysis treatment. SFP is introduced into the sodium bicarbonate concentrate that subsequently is mixed into dialysate. Once in the dialysate, SFP crosses the dialyzer membrane and enters the bloodstream where it immediately binds to apo-transferrin and is taken to the bone marrow, similar to how dietary iron is processed in the human body. In completed clinical trials to date, SFP has demonstrated that it can safely deliver iron and maintain hemoglobin levels while decreasing ESA use, without increasing iron stores.
Rockwell's lead drug candidate in late-stage clinical development is for the treatment of iron deficiency in dialysis patients and is called Soluble Ferric Pyrophosphate (SFP). SFP delivers iron to the bone marrow of dialysis patients in a non-invasive, physiologic manner via dialysate during their regular dialysis treatment. In completed clinical trials to date, SFP has demonstrated that it can safely deliver sufficient iron to the bone marrow. SFP is nearing completion of its Phase 3 clinical study program (CRUISE-1 and CRUISE-2) and is expected to address an estimated
Rockwell is preparing to launch its
Rockwell is also an established manufacturer and leader in delivering high-quality hemodialysis concentrates/dialysates to dialysis providers and distributors in the U.S. and abroad. As one of the two major suppliers in the U.S., Rockwell's products are used to maintain human life by removing toxins and replacing critical nutrients in the dialysis patient's bloodstream. Rockwell has three manufacturing/distribution facilities located in the U.S. and its operating infrastructure is a ready-made sales and distribution channel that is able to provide seamless integration into the commercial market for its drug products, Calcitriol and SFP upon
Rockwell's exclusive renal drug therapies support disease management initiatives to improve the quality of life and care of dialysis patients and are intended to deliver safe and effective therapy, while decreasing drug administration costs and improving patient convenience.
Certain statements in this press release constitute "forward-looking statements" within the meaning of the federal securities laws, including, but not limited to, Rockwell's intention to launch Calcitriol and SFP following
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