CytRx’s Arimoclomol to be Administered in a Phase 2/Phase 3 Adaptive Clinical Trial
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CytRx Corporation has announced that a Phase 2/3 adaptive clinical trial has commenced to study its molecular chaperone regulator drug candidate arimoclomol in a subset of patients with the inherited or familial form of amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease).
Patients with familial ALS (fALS) who harbor certain mutations in the superoxide dismutase-1 (SOD1) gene suffer from a progressing form of the disease. The clinical trial is being financially supported by grants from the ALS Association and the U.S. Food and Drug Administration’s (FDA’s) Office of Orphan Products Development (OOPD), with CytRx supplying the drug and allowing the sponsor to reference CytRx’s Investigational New Drug Application for regulatory purposes.
“We remain enthusiastic about the prospects for arimoclomol as a potential drug candidate for neurodegenerative disease, and are seeking a corporate partner with which to develop it,” said Steven A. Kriegsman, Chief Executive Officer of CytRx. “We are delighted that the ALS Association and the FDA’s OOPD are willing to provide all of the financial support for this Phase 2/3 clinical trial of arimoclomol in this rapidly-progressing form of ALS.”
The double-blind, placebo-controlled, adaptive clinical trial design allows for the seamless transition from a Phase 2 safety and tolerability study to a planned overlapping Phase 3 efficacy study. fALS subjects with SOD1 gene mutations will be randomized 1:1 to receive either 100 mg oral arimoclomol or a placebo three times daily. This arimoclomol dose is the same as the highest dose level administered in CytRx’s prior Phase 2a and open label clinical trials for sporadic ALS.
In addition to standard clinical safety monitoring several indicators of disease progression will also be measured including the ALS Functional Rating Scale Revised (ALSFRS-R).
Co-principal investigators for the study are Michael Benatar MBChB, MS, DPhil, Associate Professor of Neurology and Epidemiology at Emory University, and Merit Cudkowicz, MD, Associate Professor at Harvard Medical School. According to Dr. Benatar, “We are very pleased to be able to test arimoclomol in patients with mutations in the SOD1 gene. With this mutation the diagnosis of ALS can be made with confidence based on less prominent clinical features allowing initiation of treatment to begin at an earlier stage in the disease process.”
The Phase 2 trial is expected to require approximately 18 months to enroll 30 subjects who will be treated continuously for 12 months. Once the last subject has been treated for 6 months an interim analysis will be performed to determine safety, tolerability, and feasibility. This analysis will determine whether or not to proceed to the Phase 3 trial and if so, how many additional subjects would need to be enrolled to power the study sufficiently to detect at least a 30% decrease in the rate of disease progression over a 12 month period using the ALSFRS-R.
Data from these Phase 2 subjects will be included in the data analysis of the planned Phase 3 trial. If results from the Phase 2 interim analysis merit continuation to Phase 3, it is estimated that an additional 50 subjects will be enrolled. It is expected to require approximately 18 months to enroll these 50 subjects, who will be treated with either arimoclomol or placebo for 12 months as in the Phase 2 trial. Additional information regarding the clinical trial is available at clinicaltrials.gov.
Patients with familial ALS (fALS) who harbor certain mutations in the superoxide dismutase-1 (SOD1) gene suffer from a progressing form of the disease. The clinical trial is being financially supported by grants from the ALS Association and the U.S. Food and Drug Administration’s (FDA’s) Office of Orphan Products Development (OOPD), with CytRx supplying the drug and allowing the sponsor to reference CytRx’s Investigational New Drug Application for regulatory purposes.
“We remain enthusiastic about the prospects for arimoclomol as a potential drug candidate for neurodegenerative disease, and are seeking a corporate partner with which to develop it,” said Steven A. Kriegsman, Chief Executive Officer of CytRx. “We are delighted that the ALS Association and the FDA’s OOPD are willing to provide all of the financial support for this Phase 2/3 clinical trial of arimoclomol in this rapidly-progressing form of ALS.”
The double-blind, placebo-controlled, adaptive clinical trial design allows for the seamless transition from a Phase 2 safety and tolerability study to a planned overlapping Phase 3 efficacy study. fALS subjects with SOD1 gene mutations will be randomized 1:1 to receive either 100 mg oral arimoclomol or a placebo three times daily. This arimoclomol dose is the same as the highest dose level administered in CytRx’s prior Phase 2a and open label clinical trials for sporadic ALS.
In addition to standard clinical safety monitoring several indicators of disease progression will also be measured including the ALS Functional Rating Scale Revised (ALSFRS-R).
Co-principal investigators for the study are Michael Benatar MBChB, MS, DPhil, Associate Professor of Neurology and Epidemiology at Emory University, and Merit Cudkowicz, MD, Associate Professor at Harvard Medical School. According to Dr. Benatar, “We are very pleased to be able to test arimoclomol in patients with mutations in the SOD1 gene. With this mutation the diagnosis of ALS can be made with confidence based on less prominent clinical features allowing initiation of treatment to begin at an earlier stage in the disease process.”
The Phase 2 trial is expected to require approximately 18 months to enroll 30 subjects who will be treated continuously for 12 months. Once the last subject has been treated for 6 months an interim analysis will be performed to determine safety, tolerability, and feasibility. This analysis will determine whether or not to proceed to the Phase 3 trial and if so, how many additional subjects would need to be enrolled to power the study sufficiently to detect at least a 30% decrease in the rate of disease progression over a 12 month period using the ALSFRS-R.
Data from these Phase 2 subjects will be included in the data analysis of the planned Phase 3 trial. If results from the Phase 2 interim analysis merit continuation to Phase 3, it is estimated that an additional 50 subjects will be enrolled. It is expected to require approximately 18 months to enroll these 50 subjects, who will be treated with either arimoclomol or placebo for 12 months as in the Phase 2 trial. Additional information regarding the clinical trial is available at clinicaltrials.gov.
