Outstanding Preliminary Results of A Clinical Trial Treating Moderate-To-Severe Covid-19 Patients, Conducted By Amorphical, An Israeli Biotechnology Company
Ness Ziyona, Israel
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January 06, 2022 02:00 PM Eastern Standard Time
Amorphical’s Novel COVID-19 Oral and Inhaled Amorphous Calcium Carbonate (ACC) Treatment Significantly Reduces the Risk of ICU Admission and Mortality in Interim Analysis of a Phase II Study Involving Patients Hospitalized with Moderate-to-Severe COVID-19. (NIH Clinical Trial Registration No. NCT04900337)
Outstanding preliminary results were revealed in an interim analysis of an on-going Phase II clinical study in Israel for treating patients with moderate-to-severe COVID-19. AMOR-18, a new drug consisting of Amorphical’s unique amorphous calcium carbonate (ACC), was the active pharmaceutical ingredient. The preliminary analysis focused onAMOR-18’s capability of stopping the currently-acute pandemic urgencies from further harming hospitalized patients. Out of a total of 37 patients recruited in one of the study centers, none of the 18 patients taking the drug was transferred to an intensive care unit (ICU) and all were released within a few days from the hospital. In a sharp contrast, 32% of the 19 participants in the placebo group, were transferred to ICU and 10% died.
Thus far, sixty-six (66) patients were treated, six (6) in Phase I, fifty-eight (58) in Phase II and two (2) in a compassionate care program. The interim analysis is performed in one of the 4 participating medical centers (Ziv Medical Center) in which 37 moderate-to-severe patients had participated in a randomized, placebo controlled, double-blind study.19 patients were treated with placebo, and 18 patients with AMOR-18.
Last week, Amorphical announced that all 18 patients with COVID-19 , hospitalized with moderate or severe symptoms, who had received the drug AMOR-18, have recovered and were discharged within a few days. None of the patients treated with the drug were transferred to the intensive care unit or died. By contrast, among the nineteen (19) individuals in the placebo arm, six (6) were transferred to intensive care, and two of them died .As a part of Amorphical’s compassionate care program, two other patients with gravely serious conditions were given the drug outside the study in the same hospital. Both have recovered and were discharged from the hospital.
“Since none of the patients receiving the drug (AMOR-18) were transferred to intensive care or died, this interim outcome is a tremendous success for our patients and community”, said Dr. Nashat Abu Saleh, Co-Director of the Coronavirus Department at the Ziv Medical Center in Safed, Israel, where this phase II clinical trial was conducted.
Positive Interim Results
The ongoing Phase II study (AMCS-COVID-001) is a Prospective, Randomized, Placebo-Controlled, Double-Blind Study of the Safety, Tolerability, and Efficacy of ACC(namedAMOR-18), taken daily sublingually and via inhalation administration, concomitantly with Best Available Care (BAT), compared to placebo and BAT.
The first efficacy measure assesses the rate of change from baseline to study completion (hospital release or death), as defined by an improvement of 1 or more points on an ordinal 8-point scale. The second measure of efficacy is the ratio of mortality to Intensive Care Unit (ICU) admissions. The preliminary analysis was conducted on a total of 37 patients, equally randomized to treatment with either AMOR-18 (ACC) or a placebo, concomitantly with BAT. Six (6) out of the group of 19 patients (32%) treated with placebo concomitantly with BAT were transferred to the ICU, two of whom died (33%). Conversely, none of the hospitalized patients actively treated with ACC) were transferred to the ICU or died.
Dr. Kamal Abu-Jabal, Co-Director of the Outpatient Hospital Unit and ICU COVID-19 Unit at Ziv Medical Center, said:
"I believe this treatment has the potential to significantly reduce the mortality rate in patients with moderate-to-severe COVID-19 symptoms and has a broader potential for treating patients who contract similar viral infections. We found safety, effectiveness, and no side effects. Together with the treatment available today for COVID-19, Amor 18 may turn this pandemic to an illness from which one can recover relatively easily, even severely ill hospitalized patients. In our opinion, we are at a turning point of a fundamental change in dealing with COVID-19".
Yossi Ben, Founder & CEO of Amorphical, noted: "The interim results bring a great deal of interest among countries and the scientific community. Amorphical is currently conducting several negotiations for such international participation in efforts to combat the pandemic. We intend to provide preferred distribution channels to countries who will support further clinical studies, as well as assist in obtaining regulatory related activities of the drug treatment".
The Study at Glance
Initially, 6 patients (not included in the reported 37) were recruited for a Training/Safety Study (Phase I) at 3 research hospital sites in Israel. This stage assessed the safety and administration protocol of AMOR- 18 in combined sublingual and inhalable modes. This part of the study concluded that it was safe to initiate a prospective, multicenter, randomized, double-blind, placebo-controlled phase II study.
The study was originally designed to include 100 patients in total with one-on-one randomization (active + BAT vs. placebo + BAT), and conducting the Phase II study at four medical centers in Israel: Shamir, Ziv, Kaplan, and Mayanei Hayeshua. However, in December 2021, Amorphical conducted an interim analysis of the study on all 37 participating patients in one of the study institutions – Ziv Medical Center. The principal investigators at this Center are Dr. Kamal Abu-Jabal, and Dr. Nashat Abu-Saleh. The interim analysis was conducted due to the vast global spread of COVID-19, a temporary lack of patient candidates in Israel, and anurgent needfor opening study centers outside of Israel. The interim analysis was performed by an independent statistician.
The Phase II study in Israel will continue to recruit the intended 100 patients at all the specified hospitals, potentially also including the Wolfson Medical Center-Israel.
Preliminary Analysis
The study population included 37 patients who tested positive for COVID-19 according to a PCR test and were hospitalized due to the severity of their conditions. After screening, 18 patients were randomly assigned to active treatment group and 19 to a placebo group. The ICU and mortality rate analysis was assessed, along with 95% Wilson Score Confidence Intervals (CI), comparing the study arms with a Cochran-Mantel-Haenszel Test. The Intent to Treat (ITT) analysis set consists of all subjects being randomized. In accordance with the ITT principle, subjects are kept/remain in their originally assigned treatment group.
For subjects randomized for treatment by either ACC or placebo, the rate of ICU admittance or death occurred only in the placebo group, and was not observed in the treatment group (p<0.01).All patients in the ACC group tolerated the treatment well, were released from the hospital, and did not report any treatment-related adverse side effects. Further analysis of the interim resultsis on going.
According to the preliminary analysis, subjects randomly placed in the active arm (ACC) had a statistically and significantly lower risk of death or ICU admission compared to those randomized into the placebo arm. In the active arm, 0.0% (0/18, 95% CI: [0.00%;17.59%]) of the subjects died or were transferred to the ICU, vs. 31.6% (6/19, 95% CI: 15.36%;53.99%]) in the placebo arm. This difference was highly significant, (p<0.02).
The early analysis of the interim results concludes that treating moderate-to-severe COVID-19 hospitalized subjects with ACC AMOR-18is effective in reducing the risk of worsening of the disease.
In addition to the goals outlined above, Amorphical has established a compassionate use program, which has treated two additional patients with very severe COVID-19 infection and significant comorbidities. Although these patients did not meet our study inclusion criteria, both responded well to the ACC treatment and were released home.
Amorphical plans to complete phase II and immediately proceed to phase III. Phase III will further evaluate the effectiveness of ACC and confirm its safety, tolerability, and efficacy on a global scale. It will then be internationally submitted for prompt regulatory approvals with the intention to support the worldwide efforts against the current and similar future pandemics.
Amorphical is currently engaged in approval process with ANVISA (the Brazilian Health Regulatory Agency) to begin recruitment for a similar study with 100 additional patients at 7 hospital sites in Brazil.
About the ACC (AMOR-18) Therapeutic Mechanism
ACC consists of nanometric and amorphous primary particles, and has much higher solubility & bioavailability than crystalline calcium carbonate (CCC). Amorphical successfully manufactures and markets several dietary supplements based on ACC, which help build, maintain, and restore the body’s health and strength. Preclinical and early clinical studies reveal that ACC provides unique therapeutic and biomedical activities for treating diseases and conditions, associated with acidosis conditionsby directly targeting specific organs or systems.
There is a growing body of scientific literature indicating the effects of low pH (metabolic acidosisinside and around organs and cells) on: (a) the progression of SARS-type viruses in general, and COVID-19 in particular; (b) the detrimental impact of excessive acidity on lung inflammation and functions; and (c) the exaggerated immune response (expressed as a cytokine storm), leading to devastating lethal outcomes. In our current study, ACC aims to serve as a pH modulator of the extracellular compartment, inhibiting the virus cell’s penetration, and replication within body cells, and regulating abnormal immune responses. These therapeutic activities are enabled by ACC’s unique amorphous and nanometric state, combined with its carbonate component. These assumed therapeutic activities inspired the current clinical study for treating the entire range of patients suffering from mild-to-severe COVID-19 infection.
About Amorphical
Amorphical is an Israeli pioneering biotech company, established to develop health and therapeutic products based on amorphous calcium carbonate (ACC). Amorphical has succeeded in synthesizing, stabilizing, and preserving a naturally rare form of calcium carbonate used by nature’s most sophisticated “calcium-producing machine” – the blue crayfish. The synthesis and formulations have been scaled into a manufacturing GMP (Good Manufacturing Practices) operation for supplements in the Arava Desert in Israel. We develop novel solutions for numerous major diseases, based on the uniquely bioactive, nanometric and amorphous ACC. The company has applied for over 130 patent applications in over 40 countries, with over 60 patents already granted worldwide. (www.amorphical.com))
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