Afrezza With Basal Combination (ABC): Phase 4 Clinical Trial

[mango]

A new clinical trial utilizing Afrezza and sponsored by MannKind has just recently been added to the restoration Feb. 17th, 2022.

Afrezza With Basal Combination (ABC)

The Phase 4 ABC trial summary brief:

MKC-TI-192 is a Phase 4, 90-day, randomized, three-arm, multicenter clinical trial evaluating the treatment paradigm and efficacy of Afrezza in controlling postprandial glucose in adult subjects (≥18 years of age) with Type 1 Diabetes Mellitus (T1DM). Subjects will be randomized to one of three treatment groups (two Afrezza groups and one control group):

Afrezza + AID: Subjects in this group will use Afrezza for their bolus (mealtime) insulin and a continuous subcutaneous insulin infusion (CSII) pump with an automatic insulin delivery (AID) algorithm using rapid acting analogs (RAA) for their basal and correction insulin coverage.

Afrezza + Insulin Degludec: Subjects in this group will use Afrezza for their bolus (mealtime and correction) insulin and insulin degludec for basal insulin coverage.

AID Control: Subjects in this group will use a CSII pump with an AID algorithm using RAA for all bolus (mealtime and correction) and basal insulin coverage (control group).

The study is composed of up to 5 clinic visits (screening, 3 treatment visits, and an end-of-treatment visit) and 9 telephone visits.


————————————————————

This Phase 4 clinical trial is set up to make waves and looks very exciting. Completion is scheduled for September this year.


Primary Outcome Measures :
Change in HbA1c [ Time Frame: 90 days ]
Change in glycated hemoglobin (HbA1c) from baseline to end of study


Secondary Outcome Measures :
Rate of Level 1 Hypoglycemic Events [ Time Frame: 90 days ]
Event rate of hypoglycemia (SMBG <70 mg/dL)

Rate of Level 2 Hypoglycemic Events [ Time Frame: 90 days ]
Event rate of hypoglycemia (SMBG <54 mg/dL)

Rate of Severe Hypoglycemic Events [ Time Frame: 90 days ]
Event rate of severe hypoglycemia requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions

Change in Time in Range (70 - 180 mg/dL) [ Time Frame: 90 days ]
Change in percent time in range (TIR) based on continuous glucose monitoring derived glucose values

Change in Time Below Range (glucose <70 mg/dL) [ Time Frame: 90 days ]
Change in percent time below range (TBR), defined as time spent with glucose <70 mg/dL based on continuous glucose monitoring derived glucose values

Change in Percent Time with Glucose <54 mg/dL [ Time Frame: 90 days ]
Change in percent time spent with glucose <54 mg/dL based on continuous glucose monitoring derived glucose values

Change in Time Above Range (glucose >180 mg/dL) [ Time Frame: 90 days ]
Change in percent time above range (TAR), defined as time spent with glucose >180 mg/dL based on continuous glucose monitoring derived glucose values

Change in Percent Time with Glucose >250 mg/dL [ Time Frame: 90 days ]
Change in percent time spent with glucose >250 mg/dL based on continuous glucose monitoring derived glucose values

Change in Coefficient of variation (CV) [ Time Frame: 90 days ]
Change in glycemic variability as measured by coefficient of variation (CV) based on continuous glucose monitoring derived glucose values


Other Outcome Measures:
Incidence and Severity of Adverse Events [ Time Frame: 90 days ]
Incidence and severity of adverse events (AEs): treatment-emergent adverse events (TEAEs), serious AEs (SAEs), AEs of special interest (AESIs), and device complaints.

Change in Percent Predicted Forced Expiratory Volume in 1 Second [ Time Frame: 90 days ]
Change in percent predicted forced expiratory volume in 1 second (FEV1) from baseline to end of study




clinicaltrials.gov/ct2/show/NCT05243628?term=MannKind&recrs=ab&draw=1&rank=1

[derekewhitlock]

Finally!

[cjm18]

25 participants. Lol

[comnkd]

Feb 17, 2022 9:59:04 GMT -5 cjm18 said:

25 participants. Lol

A bit more context would demonstrate that 25 is the estimated target number of participants needed in the clinical study. As this is a FDA approved study, 25 is good enough for them. Do you know more about clinical study design than the FDA?

Per the linked study site:
Enrollment target is 25.
Enrollment is defined as: "The number of participants in a clinical study. The "estimated" enrollment is the target number of participants that the researchers need for the study."

[Deleted]

Feb 17, 2022 9:59:04 GMT -5 cjm18 said:

25 participants. Lol

Keep in mind it's a "STUDY" and not a Trial.   

[mango]

Feb 17, 2022 11:14:04 GMT -5 @chuckbass said:

Feb 17, 2022 9:59:04 GMT -5 cjm18 said:

25 participants. Lol

Keep in mind it's a "STUDY" and not a Trial.   

Directly from the clinical trial summary:

MKC-TI-192 is a Phase 4, 90-day, randomized, three-arm, multicenter clinical trial

[cjm18]

Feb 17, 2022 10:59:11 GMT -5 comnkd said:

Feb 17, 2022 9:59:04 GMT -5 cjm18 said:

25 participants. Lol

A bit more context would demonstrate that 25 is the estimated target number of participants needed in the clinical study. As this is a FDA approved study, 25 is good enough for them. Do you know more about clinical study design than the FDA?

Per the linked study site:
Enrollment target is 25.
Enrollment is defined as: "The number of participants in a clinical study. The "estimated" enrollment is the target number of participants that the researchers need for the study."

Is 25 good enough for sales reps to help sell Afrezza or change the soc?

[sayhey24]

I would have liked to see two levels of TIR, ideally 70-140 and 70-180 but even 70-160 and 70-180 would be a good start to get the conversation going on TIR.

[sayhey24]

Mike just mentioned this trial on the Leerink call. He also mentioned doing a PCP study in June with 25 PCPs trying to change the afrezza sales model.

[prcgorman2]

Feb 17, 2022 11:37:51 GMT -5 cjm18 said:

Feb 17, 2022 10:59:11 GMT -5 comnkd said:

A bit more context would demonstrate that 25 is the estimated target number of participants needed in the clinical study. As this is a FDA approved study, 25 is good enough for them. Do you know more about clinical study design than the FDA?

Per the linked study site:
Enrollment target is 25.
Enrollment is defined as: "The number of participants in a clinical study. The "estimated" enrollment is the target number of participants that the researchers need for the study."

Is 25 good enough for sales reps to help sell Afrezza or change the soc?

I think this is a fair question if anyone claimed the goal of the trial/study were to change the SOC.  I don’t know but will speculate it may be a strategy of conservative effort until more expansive effort is appropriate.  I’ve worked with people in marketing that would call such an approach “success-based”, meaning you try something and if it is successful, you do more.  General George Patton called it “rock soup”.

I like the approach in that I feel like overall our CEO has proven to be careful with cash.  In terms of balancing revenue and debt management with operational and development requirements, I personally think he and Binder have done outstanding.  It is good to avoid “toxic debt”, and being conservative now until revenues improve is prudent.

[mango]

Mike mentioned in the SVBLeerink fireside chat that this was a Pilot clinical trial.

[awesomo]

Feb 19, 2022 7:13:21 GMT -5 prcgorman2 said:

Feb 17, 2022 11:37:51 GMT -5 cjm18 said:

Is 25 good enough for sales reps to help sell Afrezza or change the soc?

I think this is a fair question if anyone claimed the goal of the trial/study were to change the SOC.  I don’t know but will speculate it may be a strategy of conservative effort until more expansive effort is appropriate.  I’ve worked with people in marketing that would call such an approach “success-based”, meaning you try something and if it is successful, you do more.  General George Patton called it “rock soup”.

I like the approach in that I feel like overall our CEO has proven to be careful with cash.  In terms of balancing revenue and debt management with operational and development requirements, I personally think he and Binder have done outstanding.  It is good to avoid “toxic debt”, and being conservative now until revenues improve is prudent.

Except “success-based” marketing can have turn around times in the months, it’s taken years to even get to this point in regards to trials. You want to give them another 5-10 years to feel it out?

Highly unlikely a 25 person trial will do anything to move the needle, the sample size is just too small.

[cjm18]

Feb 19, 2022 7:13:21 GMT -5 prcgorman2 said:

Feb 17, 2022 11:37:51 GMT -5 cjm18 said:

Is 25 good enough for sales reps to help sell Afrezza or change the soc?

I think this is a fair question if anyone claimed the goal of the trial/study were to change the SOC.  I don’t know but will speculate it may be a strategy of conservative effort until more expansive effort is appropriate.  I’ve worked with people in marketing that would call such an approach “success-based”, meaning you try something and if it is successful, you do more.  General George Patton called it “rock soup”.

I like the approach in that I feel like overall our CEO has proven to be careful with cash.  In terms of balancing revenue and debt management with operational and development requirements, I personally think he and Binder have done outstanding.  It is good to avoid “toxic debt”, and being conservative now until revenues improve is prudent.

That’s exactly what the trial is doing. And it’s a the right approach.

What is a pilot trial? A pilot trial is a small study conducted to help design and assess the feasibility of doing a larger, full‐scale trial.

[sayhey24]

Feb 19, 2022 9:38:49 GMT -5 awesomo said:

Feb 19, 2022 7:13:21 GMT -5 prcgorman2 said:

I think this is a fair question if anyone claimed the goal of the trial/study were to change the SOC.  I don’t know but will speculate it may be a strategy of conservative effort until more expansive effort is appropriate.  I’ve worked with people in marketing that would call such an approach “success-based”, meaning you try something and if it is successful, you do more.  General George Patton called it “rock soup”.

I like the approach in that I feel like overall our CEO has proven to be careful with cash.  In terms of balancing revenue and debt management with operational and development requirements, I personally think he and Binder have done outstanding.  It is good to avoid “toxic debt”, and being conservative now until revenues improve is prudent.

Except “success-based” marketing can have turn around times in the months, it’s taken years to even get to this point in regards to trials. You want to give them another 5-10 years to feel it out?

Highly unlikely a 25 person trial will do anything to move the needle, the sample size is just too small.

After this pilot is done Mike could make the argument to "bolster" the participates by extracting the data from the affinity-1 trial by the doctor who second dosed and whose results should be similar to what they see with this pilot study.  But, I doubt the ADA is going to entertain changing the SoC anytime soon even if the trail had hundreds in it as the affinity-1 trial did.

There is so much money in complex pumps and APs and research and with afrezza as Al use to say all you need is a simple patch pump.  The last thing the ADA wants is to mess up the gravy train of funds coming in from these companies.

With the T2s things are starting to come to critical mass as a bunch of "diet" companies are developing their protocals around use of CGMs.  At some point these companies will start adding afrezza into their protocals because there is only so much you can do with diet alone especially when their client cheat on the diet.