On The Clinical Hold; Here You Can Find An Aggregate of Information Discussing the Clinical Hold
Seemingly-Harmless made a request that I put together that what I might know about the Clinical Hold.
So, I didn't want to wait until I had the time; Rather, I do this right now and put what ever I have down and if anyone else knows more, please add to this by commenting and adding that information there in the comment sections.
Some of the questions seemingly-harmless would like answered are:
my understanding is the clinical hold happened as the data was bad/incomplete/unformatted coming from amarex.- what was the main reason for the hold?- did cytodyn initiate the hold voluntarily or did the FDA impose it?- was this due to brazil data or cd10/12 data?- what is the average time for a clinical hold? - has this been unreasonably long?- what are the metrics for us to have it lifted?- is the clinical hold reasonable?- was it because of 2 deaths in the trial?- for what indications is the hold for - HIV and covid right?- why would the FDA have a hold for some indications and not others?- will the hold cause trial validity to be erased so we have to start over?- will resolution of the hold also mean clarity/validity of trial data?- are there any long lasting problems to be expected from this?- or is it merely a pause and nothing to worry about once it is lifted?
So, Seemingly-Harmless, I'll post links and excerpts which should answer many of these, but it will be in random order and the answers will have to be found in the context of the material.
Everyone else, please try to answer the questions above in the comments below if you know the answers.
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VANCOUVER, Washington, March 30, 2022 (GLOBE NEWSWIRE) -- CytoDyn Inc. (OTCQB: CYDY) ("CytoDyn" or the "Company"), a late-stage biotechnology company developing leronlimab, a CCR5 antagonist with the potential for multiple therapeutic indications, announced that the U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on its HIV program and a full clinical hold on its COVID-19 program in the United States. Further, the Company elected to pause its Brazil COVID-19 trials pending results from its previously scheduled data safety monitoring committee meeting and is in the process of reevaluating the timing of its HIV BLA resubmission.
The Company was not enrolling any new patients in the trials placed on hold in the United States. The partial clinical hold on the HIV program impacts patients currently enrolled in extension trials. These patients will be transitioned to other available therapeutics and no clinical studies can be initiated or resumed until the partial clinical hold is resolved. CytoDyn intends to work closely with the FDA to resolve the partial clinical hold as soon as possible. Under the full clinical hold on the COVID-19 program, no new clinical studies may be initiated until the clinical hold is resolved. The Company is not currently conducting any COVID-19 trials in the United States, as it is evaluating the most optimal programs on which to focus its resources and attention.
“CytoDyn is committed to FDA compliance,” said Scott A. Kelly, M.D., Chief Medical Officer of CytoDyn. “We are evaluating our clinical programs and are working to resolve the issues underlying the clinical holds as soon as possible in close communication with the FDA. We will provide an update when we have additional information.”
The Company will host a webcast conference call to discuss this announcement and other updates on March 31, 2022 at 5:30 AM (PT) and 8:30 AM (ET). Connection details are provided below:
Date:Thursday, March 31, 2022 Time:5:30 AM PT / 8:30 AM ETAccess:Questions:https://services.choruscall.com/mediaframe/webcast.html?webcastid=v9IRoWUqPrior to the webcast, questions can be submitted online to ir@cytodyn.com
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Conference Call 3/31/22
"Scott Kelly 9:00: 2 cardiac events led to pausing CD16. they don't know if these patients are LL or placebo. They want to pause the trial b/c our experience w/LL was in healthy volunteers and not in critically ill Covid 19 population of sick individuals. They have a preplanned DSMC meeting data safety monitoring committee in early April for both studies. So upon clearance of the DSMC we plan on removing the pause. We are in communication with ANVISA and the FDA and reported the events to each agency, but this was CytoDyn's decision. Full clinical hold on US IND Covid 19, and partial clinical hold for IND for HIV. The FDA wants aggregated safety data across all indications as our prior CRO was not aggregating safety data. We will correct this. We believe this is a solvable problem. We have contracted with a new pharmaco-vigilance CRO to move forward. So we expect about an 8-12 week, (June-July 2022), timeline and seek advice from the FDA."
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Conference Call 6/30/22
Antonio Migliarese: We have been addressing and drafting the clinical holds for HIV and Covid 19 and strengthening our clinical operations and prioritizing patient safety. We have strong project team in place and will provide an update in progress towards in addressing clinical hold and provide an update on the pause on Covid 19 Brazilian trials.
18:05 Scott Kelly: Thank you Antonio. So, I would like to begin by addressing the partial clinical hold on our HIV program & clinical hold on our Covid 19 program. To provide project management timelines for submitting the necessary materials in September of this year. Our initial time frame of 8-12 weeks, was dependent on us being provided data from former CRO according to industry standards. In the process of analyzing the data, in conjunction with our pharmacovigilance experts, we realized we needed to convert the data into industry standard format. To be clear, We have the data. It is really a data conversion issue. Unforeseen data quality and other data related issues remain a risk that could impact the time line. AM, do you want to add some color on this?
18:50 Antonio Migliarese: Thanks Scott. One of the things we want to highlight is that addressing the clinical hold is our number one priority in the organization and this is an all hands on deck effort. As we mentioned earlier, we have a strong project team in place, which is led internally, by our chief top performers, who have vast industry experience including an internal project manager. This is led by our senior director of clinical operations, Joe Meidling and our vp of project management, Bernie Cunningham. We've additionally engaged in CRO, clinical research organization that has deep experience in root sources in the areas of pharmacovigilance, safety data based management analysis. We also have the regulatory consulting firm that is assisting us with the preparation and review of the various regulatory communication, and lastly we have the data to work with an overall regulatory strategy advising group. This group is one of the most reputable at being regulatory consulting firms led by former FDA regulators.
To provide a little more color on our project management, this team has a line by line detailed project plan with paths, timelines and milestones where its various team members are accountable. Our team holds a series of meetings designed to check in, discuss, progress for milestones, roadblocks and risks to the critical paths. These meetings occurs at various intervals throughout the week and the month. This allows us to identify issues as quickly as possible to trouble shoot and identify ways to overcome and impact on overall timeline. Furthermore, this allows us to identify opportunities to bring in additional resources and where if possible to expedite time.
20:33 Scott Kelly: Thanks Antonio. I will address the pausing for Covid19 Brazil trial. In consideration to potentially un-blind the data. The trials in brazil were never put on clinical hold. CytoDyn's clinical team decided to pause the Covid 19 trials in Brazil, as the Data Safety Monitoring Board DSMV, had a scheduled predetermined date to evaluate safety within a few weeks. The DSMB evaluated the safety portion only of the trial, not the efficacy, but the recommendation was to continue the trial with ongoing monitoring, and in term analysis according to the trial protocol. We are currently awaiting to hear from ANVISA. As we wait for approval to proceed with the trial, we will continue to analyze the dynamics of the Covid 19 landscape as it unfolds with a particular emphasis on the critical Covid 19 population. In regard to the potential to un-blinding of the data, we have had many people request the potential to un-blind the data early. We are considering all options and are working with our team, including our own statisticians, our Einstein clinical team in in Brazil, Einstein statisticians as well as our partner BIOMME.
The updates on our clinical programs regarding HIV BLA, there has been some concerns that we are abandoning the BLA for HIV and to be clear, we are not abandoning the HIV BLA. We are currently working to achieve the deliverables required by the FDA to lift the clinical hold. We have requested a type c meeting with the FDA to gain further guidance with respect to completion of the BLA. Once we achieve the lift on clinical hold and receive further clarities from our type c meeting request from the FDA, we will be in better position to provide an updated timeline analysis.
46:13 Christine: Why are we extended use of HIV LRM patients terminated by the FDA and forced to find another treatment? When reportedly, LRM was keeping them alive and many in remission and did Charlie Sheen find new medications?
Scott Kelly: So it was required by FDA due to the partial clinical hold of HIV as other treatment options were available for these patients and I can't comment on Charlie Sheen.
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https://clinicalinfo.hiv.gov/en/drugs/leronlimab/patient
Select clinical trials of leronlimab
On March 30, 2022, the developer’s of leronlimab announced that the U.S. Food and Drug Administration (FDA) placed a partial clinical hold on the company’s HIV program. The partial clinical hold affects participants who are enrolled in extension trials; participants in these trials will switch to other available treatment. Until the partial clinical hold is lifted, no clinical studies will be initiated or resumed. For more information about the clinical hold, please refer to the drug developer’s March 30, 2022 press release.7
Study Name: NCT00642707Phase: 2aStatus: This study has been completed.Location: United StatesPurpose: The purpose of this study was to look at the effectiveness, safety, and drug properties of different doses of leronlimab and compare leronlimab to a placebo. Leronlimab was given as monotherapy and by subcutaneous infusion.8,9Selected Study Results: Results published in The Journal of Infectious Diseases (2010) showed that leronlimab had substantial and prolonged activity against HIV. The level of antiviral reponse increased as the total amount of leronlimab administered over the treatment period increased. The greatest antiviral effect was seen with leronlimab 324 mg weekly, producing an average maximum reduction in viral load of 1.65 log10 copies/mL.9
Study Names: (1) PRO 140_CD 01; NCT02175680 and (2) PRO 140_CD 01-Extension; NCT02355184Phase: 2bStatus: PRO 140_CD 01 has been completed. The leronlimab HIV program was placed on partial clinical hold. Please refer to the ClinicalTrials.gov record and/or the drug developer’s website for updates on the status of PRO 140_CD 01-Extension.Location: United StatesPurpose: The purpose of the PRO 140_CD 01 study was to evaluate the safety and efficacy of leronlimab monotherapy for the maintenance of viral suppression in participants who had undetectable viral load levels on ART. The PRO 140_CD 01-Extension study is evaluating the long-term effectiveness and safety of leronlimab monotherapy for HIV treatment.6,7,10,11Selected Study Results: Results published in HIV Clinical Trials (2018) showed that in the CD01 study, 23 out of 41 participants (56.1%) maintained viral suppression throughout the 12 week monotherapy treatment phase. Eighteen participants did not maintain suppression during the treatment phase, with a mean time to viral rebound of 51.3 days since the initiation of leronlimab monotherapy. In the CD01 Extension study, five out of 16 participants experienced viral rebound, with a mean time to rebound of 323 days.6
Study Names: (1) PRO 140_CD 02; NCT02483078 and (2) PRO 140_CD 02 Extension; NCT02990858 and (3) PRO 140_CD02_OpenLabel; NCT03902522Phase: 2b/3Status: PRO 140_CD 02 has been completed. The leronlimab HIV program was placed on partial clinical hold. Please refer to the ClinicalTrials.gov record and/or the drug developer’s website for updates on the status of PRO 140_CD 02 Extension and PRO 140_CD02_OpenLabel.Location: United States and Puerto RicoPurpose: The purpose of the PRO 140_CD 02 study was to look at the safety and effectiveness of using leronlimab with a failing ART regimen for 1 week and then using leronlimab with an optimized ART regimen for 24 weeks. PRO 140_CD 02 Extension is designed to provide eligible participants with continued access to leronlimab. PRO 140_CD02_OpenLabel is a single-arm open-label trial.7,12–14Selected Study Results: Results from the CD 02 trial presented at ASM Microbe 2019 showed that 64% of participants who received a single subcutaenous dose of leronlimab had a significant reduction in viral load levels from baseline after 1 week, as compared to 23% of participants who received placebo.15
Study Names: PRO 140_CD03; NCT02859961 and (2) PRO 140_CD03 Extension; NCT05271370Phase: 2b/3Status: The leronlimab HIV program was placed on partial clinical hold. Please refer to the ClinicalTrials.gov record and/or the drug developer’s website for updates on the status of PRO 140_CD03 and PRO 140_CD03 Extension.Location: United StatesPurpose: The purpose of the PRO 140_CD03 study is to evaluate the safety and effectiveness of leronlimab monotherapy for the maintenance of viral suppression in participants who had undetectable viral load levels on ART. The PRO 140_CD03 Extension study is evaluating the long-term safety and effectiveness of leronlimab monotherapy.4,7,16Selected Study Results: Preliminary results presented at CROI 2019 indicated that the majority of participants who received higher weekly subcutaneous doses of leronlimab (525 mg and 700 mg) were able to maintain viral suppression.17
For more details on the studies listed above, see the Health Professional version of this drug summary.
What side effects might leronlimab cause?What side effects might leronlimab cause?
What side effects might leronlimab cause?
One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in some of the studies of leronlimab listed above.
In this Phase 2a study, the most common side effects that were associated with either placebo or leronlimab included the following: diarrhea, headache, swollen lymph nodes, and high blood pressure. Side effects occurring at or around the injection site were mild and temporary and included hardening of the tissue, pain, and irritation.9
PRO140_CD 01 (NCT02175680) and PRO 140_CD 01-Extension (NCT02355184):
Safety data from 41 participants in the CD_01 study and 16 participants in the CD_01-Extension study found no serious side effects related to leronlimab treatment or study discontinuations due to a side effect. In both studies, mild and temporary local injection site reactions accounted for all of the side effects that were related to the study drug.6,10,11
PRO 140_CD 02 (NCT02483078); PRO 140_CD 02 Extension (NCT02990858):
In the CD_02 study, 52 participants were randomly assigned to either the leronlimab or placebo group. Final results from the study showed that 65.4% of participants experienced at least one side effect and 19.23% of participants had at least one treatment-related side effect. One participant discontinued treatment because of a side effect. No treatment-related serious side effects were reported. Injection site reactions that occurred during the study were mostly mild and went away on their own. Forty participants have enrolled into the CD_02 Extension study.12,13,15
PRO 140_CD03 (NCT02859961):
In the ongoing CD03 trial of leronlimab monotherapy, preliminary data was presented on 226 participants in the 350-mg dose group, 115 participants in the 525-mg dose group, and 43 participants in the 700-mg dose group. Thus far, the incidence and severity of side effects have not increased with the dose. Most side effects were mild in intensity and no side effect pattern was observed. None of the serious side effects that occurred were related to leronlimab. The majority of injection site reactions were mild and went away on their own.4,17
Because leronlimab is still being studied, information on possible side effects of the drug is not complete. As testing of leronlimab continues, additional information on possible side effects will be gathered.
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https://stocktwits.com/Cytomight/message/483658418
The partial hold is on what group? Extension arm? Is that monotherapy group? Is combo group still going? Who is paying for combo therapy trials?
https://investorshangout.com/post/view?id=6467676#ixzz7eLl6kBek
This is what we know, sfaik:
The U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on its HIV program and a full clinical hold on its COVID-19 program in the United States. Further, the Company elected to pause its Brazil COVID-19 trials pending results from its previously scheduled data safety monitoring committee meeting and is in the process of reevaluating the timing of its HIV BLA resubmission.
The Company was not enrolling any new patients in the trials placed on hold in the United States. The partial clinical hold on the HIV program impacts patients currently enrolled in extension trials. These patients will be transitioned to other available therapeutics and no clinical studies can be initiated or resumed until the partial clinical hold is resolved. CytoDyn intends to work closely with the FDA to resolve the partial clinical hold as soon as possible. Under the full clinical hold on the COVID-19 program, no new clinical studies may be initiated until the clinical hold is resolved. The Company is not currently conducting any COVID-19 trials in the United States, as it is evaluating the most optimal programs on which to focus its resources and attention.
https://stocktwits.com/ohm20/message/483798090
According to Cytodyn the partial hold shut down the extension trials. Which makes absolutely no sense. A partial hold will close off a certain trial protocol or parts of a protocol but not others. The only protocols active are the extensions if those are shut down then it is a complete hold.
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Posted Sep 9, 2022, 1:44 AM UTC · edited