The multi-center trial will determine the pharmacokinetics (how the body metabolizes, distributes, and excretes a drug) of subcutaneous RA101495 in these patients.
RA101495 is a new synthetic inhibitor of complement component 5 (C5), an important protein in the innate immune system, which regulates inflammation and defends against pathogens.
The invesigational therapy binds to C5 (which breaks down into the proteins C5a and C5b) with high affinity. RA101495 inhibits its cleavage onto C5a and C5b upon activation of the complement system.
RA101495 binds to a region of C5 corresponding to C5b, which disrupts the interaction between C5b and the protein C6, preventing assembly of the membrane attack complex (MAC), an important innate immune effector that forms pores on the surface of microbes. This represents a new mechanism for the inhibition of C5.
RA101495 could have a therapeutic benefit in diseases such as lupus nephritis (LN) and atypical hemolytic uremic disorder (aHUS).
“Building on the clinical data collected to date from which we observed the favorable [pharmacological] profile of RA101495, this Phase 1b trial is designed to evaluate RA101495 in a subset of patients with renal impairment, with the aim of expanding the range of indications for RA101495 as a potential therapy for patients with complement-mediated disorders,” Ramin Farzaneh-Far, MD, chief medical officer at Ra Pharmaceuticals, said in a press release.
“C5 is a clinically validated target for multiple complement-mediated renal disorders, including aHUS, and this trial is designed to provide the necessary [pharmacokinetic] data to support the future evaluation of RA101495 in renal disorders,” Farzaneh-Far added.
Researchers plan to enroll approximately 16 subjects, including eight patients with severe renal impairment and eight healthy people as controls. Each participant will receive a single dose of 0.3 mg per kg body weight of RA101495.
“The initiation of dosing in this Phase 1b trial is a meaningful step for advancing RA101495 in multiple complement-mediated renal indications,” said Doug Treco, PhD, president and CEO of Ra Pharmaceuticals. “The convenient, once-daily, SC, self-administration dosing profile of RA101495 provides a compelling alternative to currently available, intravenously-administered therapies, and we continue to work toward providing a differentiated treatment option for these patients and addressing this significant unmet need.”
“Following our recently reported positive interim data from the RA101495 Phase 2 program in PNH, we look forward to expanding the scope of RA101495 with the goal of maximizing its potential as a safe, well-tolerated, convenient, and efficacious C5 inhibitor for patients with complement-mediated disorders,” Treco added.