FDA’s clinical trial guidance stresses patient safety, studies’ integrity amid outbreak

Agency outlines its thinking around changes to clinical studies during the coronavirus outbreak

As disruptions begin to mount among biopharmas’ planned or ongoing clinical trials during the COVID-19 outbreak, newly issued FDA guidance clarified the agency’s thinking on how sponsors can ensure participants’ safety and implement modifications to clinical trials while minimizing risks to the studies’ integrity.

In the document, issued Wednesday, FDA acknowledged that studies can be affected in many ways: by quarantines, site closures, travel limitations, supply chain interruptions, or infections of study site personnel or trial subjects. Any of those, or a combination of factors, can make it harder to meet study protocols and lead to deviations.

The agency recommended that if sponsors, investigators and institutional review boards (IRBs) have not already done so, they should consider adding or revising policies and procedures to their trial plans in case of disruptions.

The guidance says sponsors may explore alternate methods of assessing patients’ safety beyond in-person evaluations, including phone contacts, virtual visits or new locations for assessment. It allows for the possibility of remote monitoring of clinical sites as well.

FDA urged sponsors to prioritize trial participants’ safety while keeping them informed.

The agency urged sponsors to prioritize trial participants’ safety while keeping them informed of any changes in recruitment, use of investigational products or monitoring. In the event participants lose access to an investigational product, it encourages additional safety monitoring.

For any changes to study protocols, efficacy assessments or trial endpoints, the guidance recommends early consultation with review boards, consultations with agency reviewers, and proper documentation.

Any changes to study processes should be “consistent with the protocol to the extent possible,” with rationale and effects documented as well.

In cases involving “immediate hazards” or other factors that can “protect the life and well-being” of participants, sponsors may implement changes without board review, but must report them afterward. The guidance encouraged sponsors “to work with their IRBs to prospectively define procedures to prioritize reporting of deviations that may impact the safety of trial participants.”

In BioCentury’s survey of biopharma executives completed in early March, 19% said their companies were likely to delay a clinical trial, while 44% said it was possible and 37% said it was unlikely (see “Survey: Action Lags Concern”; “Hidden Consequences”).

The document is labeled as final guidance. Rather than issue a draft and seek public comments, FDA wrote that given the “public health emergency” around COVID-19, the agency “determined that prior public participation for this guidance is not feasible or appropriate.”

The agency also postponed all domestic routine surveillance facility inspections Wednesday, though for-cause inspection assignments will proceed “if mission critical.” Last week, FDA halted most foreign inspections scheduled for March and April (see “FDA Postpones Meetings and Inspections”).

Trials tripped up

The guidance arrives as a handful of biopharmas have announced snags to their trial plans. More are sure to follow.

On Wednesday, Iveric bio Inc. (NASDAQ:ISEE) said it would delay the start of patient enrollment in the planned Phase III ISEE2008 trial of C5 inhibitor Zimura avacincaptad pegol to treat geographic atrophy secondary to dry age-related macular degeneration (AMD). The study is to enroll elderly patients, and Iveric cited caution for their safety.

Meanwhile, Switzerland’s Addex Therapeutics Ltd. (SIX:ADXN; NASDAQ:ADXN) postponed the start of a Phase III trial of allosteric modulator dipraglurant to treat levodopa-induced dyskinesia in patients with Parkinson’s disease. The company said the patient population is in the highest-risk category for COVID-19.

Late Tuesday, Arrowhead Pharmaceuticals Inc. (NASDAQ:ARWR) said it would pause for at least four weeks patient screening in the Phase II/III SEQUOIA trial and the Phase II AROAAT2002 trial of ARO-AAT to treat AAT deficiency, citing increased risk of severe illness among older adults and those with chronic lung disease.

On Monday, disease interception company Provention Bio Inc. (NASDAQ:PRVB) paused randomization in the Phase III PROTECT study of teplizumab to treat Type I diabetes due to COVID-19 (see “Diabetes Trial on Hold”).

Further analysis of the coronavirus crisis can be found at https://www.biocentury.com/coronavirus. The COVID-19 content found on this page, which details policy developments, scientific advances, and progress on countermeasures, is free to all who visit the site.


AAT (A1AT; SERPINA1) - α-1 antitrypsin

C5 - Complement 5

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