Evaluate Safety and Efficacy of Apitox Add-on Therapy for Improving Disability and Quality of Life in MS Patients

Multiple Sclerosis Clinical Trial

Official title: Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Safety and Efficacy of Apitox Add-on Therapy for Improving Disability and QOL in MS Patients

Status Not yet recruiting

Clinical Trial Summary

Determine the effects of Apitox add-on therapy on the progression of disability in all forms of multiple sclerosis (MS) utilizing the Expanded Disability Status Scale (EDSS) and the MS Functional Composite (MSFC) measure. b. Evaluate the safety and tolerability of add-on Apitox therapy for the treatment of patients with all forms of MS: relapsing-remitting MS (RRMS), primary progressive MS (PPMS) and secondary progressive MS (SPMS). The

Clinical Trial Description

The primary efficacy endpoints will assess the effects of Apitox add-on therapy on the changes in EDSS and the MSFC measure from baseline (average Week -1 and Week 1 pre-dose) to Week 16 (Visit 21) versus placebo (histamine). The primary safety endpoint will evaluate, at specified visits, the effects of Apitox add-on therapy on adverse events and tolerability, vital signs, clinical laboratory values, urine pregnancy test, physical exam and 12-Lead ECG. Secondary endpoints will determine the effects of Apitox add-on therapy versus placebo on the improvement in: 1. Quality of life as measured by the MSQoL-54 questionnaire at baseline (average Week -1 and Week 1 pre-dose) and Weeks 3 (Visit 8), Week 10 (Visit 15), Week 15 (Visit 20), Week 16 (Visit 21), Week 17 (Visit 22) and Week 19 (Visit 23). 2. Ambulatory and functional disability as measured by the individual Functional System Scores (FSS) at baseline (average Week -1 and Week 1 pre-dose) and Visits 8, 15, 20, 21, 22 and 23. 3. Progression of disability utilizing the change in EDSS and MSFC obtained at baseline (average Week -1 and Week 1 1 pre-dose) and Visits 8, 15, 20, 21, 22 and 23. 3. Progression of disability utilizing the change in EDSS and MSFC obtained at baseline (average Week -1 and Week 1 pre-dose) and assessed at and Visits 8, 15, 20, 22 and 23. 4. Pain and physical function as assessed with the Pain Intensity Numerical Rating Scale (PI-NRS) and Patient Global Impression of Change (PGIC) at baseline (average Week -1 and Week 1 pre-dose) and Visits 8, 15, 20, 21, 22 and 23. 5. Disease status using Patient Global Assessment (PGA), and Physician's Global Assessment (PhGA) at baseline (average Week -1 and Week 1 pre-dose) and Visits 8, 15, 20, 21, 22 and 23. Exploratory endpoints will assess, in a subset of subjects, changes in MS lesions from baseline (Week -2 or within the past 52 weeks) . Prior to randomization, subjects will undergo a skin test with Apitox (50 micrograms) to exclude those with systemic hypersensitivity to the product. Subjects will continue taking their regular MS treatments throughout the study. During the study, subjects will receive an additional 1 gram ascorbic acid per day and must not consume alcohol. After a screening period of up to 3 weeks, approximately 436 eligible subjects will be randomized in a 1:1 ratio to either Apitox (n=218) or Placebo (n=218). The fixed histamine placebo dosage was designed to be sub-therapeutic and mimic the sensation of a bee sting. All injections will be administered intradermally according to the schedule and anatomical sites provided in Appendix 1, twice weekly for 3 weeks, and then once weekly for another 12 weeks. Each subject's starting dose will be 0.2 mL (Week 1; Visit 3) and will be escalated at every visit in 0.2 mL increments up to the maximum dose of 1.5 mL (1500 micrograms at Week 4; Visit 9). At Visits 9 through 20, subjects will continue to receive 1.5 mL Apitox or placebo for the rest of the study. A subset of the randomized subjects (n=44) will undergo MRI testing for exploratory analyses of changes in MS lesions at follow-up Visit 21 (Week 16). There are 3 follow up visits (Visits 21, 22 and 23) at 1, 2 and 4 weeks post-treatment after the last maximum dose visit (Week 15; Visit 20). During treatment, visits should be at least 3 days apart. The duration of the study is up to 22 weeks that includes up to 3 weeks of screening, 15 weeks on treatment, and 4 weeks for follow-up visits. If a subject experiences an exacerbation of MS during the study, he or she should inform the site as soon as possible. The subject's primary care physician will be consulted if appropriate additional treatment can be performed at the site; e.g. intravenous (IV) corticosteroids. The primary care physician and PI will determine if the subject will continue in the trial. If the subject is discontinued, she or he will have an early termination (ET) visit. If a subject experiences an immediate or delayed hypersensitivity reaction from Apitox or histamine study treatments, the subject will undergo emergency procedures described in Sections 5.4.5 and 5.4.6. Dosing will be carried out at clinical sites in geographical areas with access to emergency facilities (i.e., near hospital or clinic with an Emergency Care Facility). Each site has personnel trained in emergency response including cardiopulmonary resuscitation (CPR), and each has rescue parenteral epinephrine available. Before discharge at Week 1 (Visit 3), each subject will be provided epinephrine for the treatment of anaphylactic shock (e.g. EpiPen® Auto-Injector) and will be advised that this should always be available to them. In the event of a severe anaphylactic reaction, subjects will stop Apitox therapy and will be discontinued from the study. This study will be monitored by a Safety Monitoring Committee (SMC). The SMC will be comprised of an independent physician, the Medical Monitor and the Investigator. The independent physician is not directly affiliated with the protocol under review. The SMC will meet to review the safety of subjects who participate in the trial and will meet, if required, to advise the sponsor if enrollment and dose escalation should continue for a specific subject ;

Related Conditions & MeSH terms

• Multiple Sclerosis

• NCT number: NCT03710655
• Study type: Interventional
• Source: Apimeds, Inc.
• Contact: Robert Brooks, PhD
• Phone: 3027321358
• Email: dbrooks3@apimeds.com
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: April 2019
• Completion date: November 2019