2 global itepekimab Phase 3 trials for COPD open new US sites

AERIFY trials still recruiting former and some current smokers, ages 40-85

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by Lindsey Shapiro PhD |

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Two international Phase 3 clinical trials testing the investigational antibody itepekimab in people with chronic obstructive pulmonary disease (COPD) are continuing to enroll patients — specifically, former smokers — at hundreds of centers worldwide, with several new sites recently opened in the U.S.

All of the new sites are being provided by Care Access, a global research company that supports trial sponsors in reaching local communities and expanding trial access. Interested COPD patients can learn more on the company’s COPD studies page.

One of the trials also is recruiting current smokers with COPD at sites in three states.

Called AERIFY-1 (NCT04701983) and AERIFY-2 (NCT04751487), the similarly-designed trials mainly aim to evaluate itepekimab’s safety and ability to reduce dangerous lung symptom flare-ups, or pulmonary exacerbations, in former smokers, ages 40-85, with moderate-to-severe COPD.

“COPD can make everyday living very difficult and exacerbations of this disease may be life-threatening,” Ali Bajwa, MD, a Care Access principal investigator of AERIFY-1, said in a press release concerning new sites in the Greater Houston area. “This study seeks to better understand how to reduce the risk of exacerbation and help improve the quality of life of those with COPD.”

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New trial sites now open in Texas, Ohio, Pennsylvania and the Carolinas

Overall, AERIFY-1 plans to enroll about 960 participants, all former smokers. The newly opened U.S. locations for this trial are in Houston, Conroe, Lake Jackson, and Webster, in Texas, and in Hamilton and Middletown, in Ohio — both located in Butler County.

“About one in thirteen adults in Butler County are living with COPD, which is concerning because that’s higher than the national average,” Michael Gabrilovich, MD, another of the trial’s Care Access investigators, said in a separate press release.

“COPD flare-ups can cause further damage to the lungs, so it’s important to prevent them, if possible,” Gabrilovich added.

The AERIFY-2 trial, meanwhile, is seeking up to 1,210 participants globally — including not only 930 former smokers but also 280 current smokers.

Newly opened sites for this study are in three U.S. states: in Pennsylvania, in Wyomissing; in South Carolina, in Rock Hill; and in North Carolina, in Mooresville.

“About seven percent of adults in Pennsylvania are living with COPD, and Berks County [including Wyomissing] has a higher rate of COPD-related hospitalization than other parts of the state,” Alec Platt, MD, the Care Access investigator for AERIFY-2 in Wyomissing, said in a press release.

Having access to this global study … is an important opportunity for local residents dealing with this condition.

In another press release, Arun Adlakha, MD, the Care Access investigator for the trial in Rock Hill, said that “approximately one in fourteen adults in South Carolina have COPD, which is higher than the national average.”

“Offering this study here locally makes it convenient for those in our community who want to join,” Adlakha said.

Added Platt, from the Pennsylvania site, “having access to this global study … is an important opportunity for local residents dealing with this condition.”

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Trials designed to confirm safety, efficacy of itepekimab in former smokers

COPD is an inflammatory lung disease characterized by respiratory symptoms such as chronic cough, wheezing, and breathing difficulties. Acute symptom exacerbations contribute to accumulating lung damage and may be life-threatening, requiring hospitalization.

In codevelopment by Sanofi and Regeneron, itepekimab is an antibody that blocks interleukin-33 (IL-33), an inflammatory signaling molecule that’s implicated in COPD.

IL-33 is released by airways cells in response to cellular stress or damage, such as that caused by cigarette smoke, allergens, or environmental pollutants, which in turn initiate and amplify multiple inflammatory cascades.

Preclinical research has shown that an IL-33 blockade reduced airway inflammation and tissue damage in a mouse model of chronic lung inflammation. Moreover, genetic variants linked to lower IL-33 function have been associated with a reduced risk of COPD.

As such, itepekimab, administered through subcutaneous or under-the-skin injections, is expected to help prevent pulmonary exacerbations in people with COPD.

The therapy was well tolerated by healthy volunteers a Phase 1 trial (NCT02958436) completed in 2017. Itepekimab then was tested against a placebo among 343 adults with COPD in a proof-of-concept Phase 2 trial (NCT03546907).

The participants were randomly assigned to receive either itepekimab (300 mg) or a placebo, once every two weeks for a minimum of about six months and up to a year, while continuing on inhaled standard-of-care.

The trial failed to achieve its overall goal of a significant reduction in annual pulmonary exacerbation rates with itepekimab relative to a placebo. But significant exacerbation reductions and lung function improvements were observed in the subgroup of patients who were former smokers.

Additional analyses indicated that itepekimab significantly reduced the risk of hospitalizations or emergency department visits by 70% among former smokers compared with a placebo.

These ongoing Phase 3 studies are designed to confirm the safety and efficacy of itepekimab among former smokers with COPD. In both, participants are randomly assigned to receive subcutaneous injections of either itepekimab or a placebo, once every two or four weeks, for up to a year while continuing on inhaled standard therapies.

The main goal is to evaluate differences in the annual rate of moderate to severe COPD exacerbations in former smokers. Secondary goals include measures of lung function, respiratory symptoms, itepekimab concentrations in the blood, and the development of antibodies against the therapy, as well as safety.

In AERIFY-2, the smaller group of current smokers will receive itepekimab or a placebo every two weeks, and changes in their pulmonary exacerbations and lung function will be assessed as additional secondary goals.

Patients completing either trial will have the option of continuing itepekimab treatment in a long-term extension study. Both trials are expected to finish in 2025.

Another Phase 2 trial, called AERIFY-3 (NCT05326412), is evaluating the effects of itepekimab on airway inflammation in former and current smokers with COPD, ages 40-70. The study, also set to end by 2025, may still be enrolling up to 60 participants at sites in the U.S. and Europe.