KRN5500 from DARA: new promise?

KRN5500  is available as a solution for intravenous (IV) administration.  Safety and efficacy data from Phase I trials are finilized and a  Phase 2a clinical trial in order to analyse the potential of KRN5500  for the treatment of neuropathic pain in cancer patients is under way.

KRN5500 in neuropathic pain: results phase II

In September 2010 new data were released by the company.

The data came from the study results from a Phase II multicenter, placebo controlled, double-blind, randomized dose escalation study for KRN5500, presented at the 13th World Congress on Pain held rin september 2010 in Montreal.

The study was designed to evaluate the safety and efficacy of KRN5500 for treatment of neuropathic pain in patients with cancer. KRN5500 was administered in escalating dose of .6, 1.2, 1.8, or 2.2 mg/m2 in IV infusion of normal saline.

Prevalence of Chemotherapy-induced Peripheral Neuropathy (CIPN) is reported to be as high as 38% in patients who receive multi-agent chemotherapy.

Endpoints and results of study KRN5500:

Primary Outcome Measures:Average pain intensity over the previous 24 hours as measured by a numeric rating scale (NRS) ranging from 0 to 10 where 0 represents "no pain" and 10 represents the "worst possible pain." [ Time Frame: Weekly for 10 weeks plus 30 day followup ] [ Designated as safety issue: No ]

Secondary Outcome Measures:Physical Examination, Vital signs and body weight, Electrocardiogram, Laboratory parameters, Adverse events, Clinical Opiate Withdrawal Scale, rescue medication, Proportion of patients who achieved a 33% reduction in pain intensity [ Time Frame: Weekly for 10 weeks plus 30 day followup ] [ Designated as safety issue: Yes ] 

Results as reported by DARA 

In an exploratory analyses of a subset of study patients with CIPN (17 of 19 total) the Wilcoxon Rank Sum test was used to compare treatment differences in median changes from baseline in pain scores recorded by patients in a daily diary. KRN5500 significantly reduced neuropathic pain when compared to placebo (27% vs. 0%; p = 0.03) when looking at best response to treatment regardless of dose or timing. 0% response is of course very odd and needs explanation, as the placebo response of IV treatment is in general very high.

For the best response within 7 days of last treatment given, the difference was in favor of KRN5500, but was not statistically significant (16% vs. 0%; p=0.19). In addition, regression analysis of the best response for each patient over doses showed a significant linear decrease in pain intensity with increase in dose (slope = -18.2; p = 0.009). 

This analysis is sadly enough just in a subset of patients, and there is no information presented about the exact numbers of patients entering the study. Probably in total 19 patients enetered, and no details have been given about the ITT analysis, which is not a good sign we believe.

Centre for the study and treatment of neuropathic pain and neuropathy in Soest, the Netherlands

This site helps patients and treating physicians, neurologists, anesthesiologists and other pain specialists to find the best and most up to date research findings related to neuropathy and neuropathic pain and the treatment thereof.

In our centre we are specialised in treating patients suffering from neuropathic pain and neuropathy following an Integrated Medicine concept. Part of our activities are within the field of consultation. We assist pharmaceutical companies in R&D strategies related to finding new drugs to treat neuropathic pain and neuropathy.

September 2010: Jan M. Keppel Hesselink, MD, PhD