What is a CAP score, and how do I calculate it?
The score is often used to determine eligibility in Huntington's clinical trials
I recently watched a webinar hosted by the Huntington’s Disease Society of America that highlighted the new Roche/Genentech clinical study, GENERATION HD2 (NCT05686551), which is testing tominersen in people with Huntington’s disease (HD).
I was enthused to hear all of the questions from the community that weren’t easy for the Roche team to answer. Topics included inclusion and exclusion criteria, and participants in the previous clinical trial, GENERATION HD1 (NCT03761849), who aren’t eligible for this new study.
One question came up (at the 20:27 mark) that caught my attention and has had me thinking a lot lately: How is a person’s CAP score determined?
Why do I need to know?
What I’ve learned is that the CAP score is a popular formula used a lot in HD clinical trials to help statisticians equally compare trial participants who are of different ages and have a different number of CAG repeats in the HTT gene, which is broadly indicative of the severity of the Huntington’s-causing mutation.
A CAP score is also used in many HD studies as key inclusion criteria, meaning that your CAP score needs to be in a certain range to qualify for the study. It’s an important piece of knowledge that I believe everyone should start to keep in their head — along with the number of CAG repeats people have, based on genetic testing — if they want to participate in trials.
However, figuring out a CAP score is not a simple matter of addition. I’ve learned that the CAP score equation can be different depending on the clinical trial. The best website I’ve found for understanding this is Enroll-HD, which breaks down one of the mathematical equations. There are also a handful of papers online that you can easily find with a search engine.
What I’ve learned
One CAP score that seems to be widely adopted has a calculation with two constants and two variables. It looks like this: CAP = Age at Study Entry x (CAG Length – L) / K; where L = 30 and K = 6.49. (L and K are constants.)
I’ve read that the Phase 3 clinical trial for SAGE-718 (NCT05655520), which is sponsored by Sage Therapeutics and is currently recruiting, uses this calculation. Recruiters are looking for participants to have a CAP score of 90 or more.
Let’s use the example of someone who is 40 years old and has 42 CAG repeats. To figure out their CAP score, you would use the following equation: 40 x (42-30) / 6.49 = 73.96, which is not equal to or greater than 90. So this person likely wouldn’t qualify for the study.
Another example would be a 40-year-old with 48 CAG repeats. The equation would be: 40 x (48-30) / 6.49 = 110.94. So this person likely would qualify for the study. There are, of course, other factors that could exclude this person from the study, so it’s always best to contact a clinical trial site and speak with a clinical trial coordinator to see if you qualify.
To make things even more confusing, the GENERATION HD2 study uses a slightly different formula to calculate the CAP score. Their formula is: Age x (CAG – 33.66). This study is looking for people in the 400-500 range.
Using the same examples as above, a person who is 40, with 42 CAG repeats, would calculate CAP as follows: 40 x (42-33.66) = 333.6, which is not in the CAP score range the study is looking for, so this person may not qualify.
The second example for this trial is a 40-year-old with 48 CAG repeats. So, 40 x (48-33.66) = 573.6; meaning, this person’s CAP score is too high, so they also may not qualify.
The sweet spot for this trial for someone who is 40 would be between 44 and 46 CAG repeats. As I mentioned in the earlier example, it’s always best to contact a clinical trial coordinator to determine whether or not you qualify.
I feel like I just went back to high school math class, but I decided to discuss this topic for a couple reasons. Firstly, I want people affected by HD who want to sign up for a clinical trial to understand more about the inclusion and exclusion criteria. Secondly, I want pharmaceutical companies and clinical trial sites to start making it easier for people to understand whether they qualify for a trial.
The CAP score is just one factor used in determining clinical trial participation, and I hope to write about a few others in future columns, if there is an interest from readers. Please let me know in the comments below, and as always, thanks for reading.
Note: Huntington’s Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Huntington’s Disease News or its parent company, Bionews, and are intended to spark discussion about issues pertaining to Huntington’s disease.
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Comments
J.
This is a super helpful article. As a cure cannot come fast enough, and many are willing to do whatever it takes to help find a cure, this translation of what a CAP is and how it is calculated is most appreciated. Thank you.