NTLA-2001 for ATTR-CM

Recruiting at 146 trial locations

Overseen By Trial Manager at Intellia

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Intellia Therapeutics

Must not be taking: RNA silencers, Tafamidis

Disqualifiers: NYHA Class IV HF, Hepatitis, HIV, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 1 day

765 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial is testing a new treatment, NTLA-2001, for individuals with ATTR-CM, a heart condition involving abnormal protein deposits. The researchers aim to determine if a single dose of NTLA-2001 can improve symptoms and ensure safety compared to a placebo (an inactive substance). This trial may suit those diagnosed with ATTR amyloidosis with heart issues and stable heart failure symptoms. As a Phase 3 trial, it represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot have used RNA silencer therapy like patisiran, inotersen, or eplontersen within the last 12 months, and you cannot start tafamidis or acoramidis within 56 days before the study.

Is there any evidence suggesting that NTLA-2001 is likely to be safe for humans?

Research has shown that NTLA-2001 was safe in earlier studies. Participants in these studies experienced a significant drop in transthyretin (TTR) protein levels, which is crucial for treating ATTR amyloidosis. This suggests the treatment is working as intended.

Regarding safety, previous participants tolerated NTLA-2001 well, with no major safety issues reported. The treatment involves a single dose administered through an IV, and while some side effects occurred, they were usually mild. Since this trial is in a later stage, NTLA-2001 has already demonstrated sufficient safety in earlier research. This is encouraging for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ATTR-CM?

NTLA-2001 is unique because it uses CRISPR technology to directly edit genes in the liver, offering a groundbreaking approach to treating ATTR-CM. Unlike current treatments like tafamidis or diflunisal, which primarily aim to stabilize or clear misfolded proteins, NTLA-2001 targets the root cause by potentially eliminating the production of the problematic transthyretin protein. This one-time intravenous infusion could drastically reduce the need for ongoing medication, which is a significant shift from the lifelong management strategies currently in place. Researchers are excited because this approach not only promises to halt disease progression but could also potentially reverse some of the damage caused by the condition.

What evidence suggests that NTLA-2001 might be an effective treatment for ATTR-CM?

Research has shown that NTLA-2001, a gene-editing treatment, may help treat ATTR-CM, a heart condition caused by a buildup of the protein transthyretin (TTR). In this trial, participants will receive either a single intravenous (IV) infusion of NTLA-2001 or a placebo. Studies have found that just one dose of NTLA-2001 can significantly and lastingly reduce TTR protein levels in the blood. Lowering TTR levels can help stabilize or even improve the condition. Early results also suggest that NTLA-2001 is generally well tolerated by patients. These findings strongly suggest that NTLA-2001 could be effective for people with ATTR-CM. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for people with a heart condition called ATTR-CM, which involves abnormal protein deposits in the heart. Participants must have a confirmed diagnosis, stable heart failure symptoms, and specific levels of NT-proBNP (a heart failure marker) in their blood.

Inclusion Criteria

My heart failure symptoms are stable and well-managed for the last 28 days.

I have a history of heart failure.

I have been diagnosed with ATTR amyloidosis affecting my heart.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous infusion of NTLA-2001 or placebo

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• NTLA-2001

Trial Overview The study is testing NTLA-2001's effectiveness and safety against a placebo. It's given as a single dose to see if it can help patients with ATTR-CM. The trial randomly assigns participants to receive either NTLA-2001 or placebo.

How Is the Trial Designed?

Group I: NTLA-2001 Experimental Treatment 1 Intervention

Single intravenous (IV) infusion of NTLA-2001

Group II: Placebo Placebo Group 1 Intervention

Single IV infusion of normal saline

Who Is Running the Clinical Trial?

Intellia Therapeutics

Lead Sponsor

Trials

10

Recruited

1,300+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Citations

1. ir.intelliatx.com ir.intelliatx.com/news-releases/news-release-details/intellia-announces-positive-two-year-follow-data-ongoing-phase-1

Intellia Announces Positive Two-Year Follow-Up Data ... A single dose of nex-z leads to deep, durable and consistent reductions in serum TTRs, with evidence of disease stability or clinically meaningful improvements.

2. ir.intelliatx.com ir.intelliatx.com/news-releases/news-release-details/intellia-therapeutics-provides-update-magnitude-clinical-trials

Release Details Nex-z is designed to inactivate the TTR gene that encodes for the transthyretin (TTR) protein and is currently being investigated in MAGNITUDE ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2107454

CRISPR-Cas9 In Vivo Gene Editing for Transthyretin ... NTLA-2001 is an in vivo gene-editing therapeutic agent that is designed to treat ATTR amyloidosis by reducing the concentration of TTR in serum.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06128629

NCT06128629 | MAGNITUDE: A Phase 3 Study of NTLA- ... To evaluate the efficacy and safety of a single dose of NTLA-2001 compared to placebo in participants with ATTR-CM. Detailed Description. This is a ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37928601/

Lessons from the first-in-human in vivo CRISPR/Cas9 ... This study showed a significant and consistent reduction in serum TTR protein levels after a single admission, while being generally well tolerated.

6. ir.intelliatx.com ir.intelliatx.com/news-releases/news-release-details/intellia-therapeutics-announces-positive-longer-term-phase-1

Release Details One dose of nex-z led to rapid, deep and durable TTR reductions, with mean reductions of at least 90% from baseline sustained through three ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04601051

NCT04601051 | Study to Evaluate Safety, Tolerability ... This study will be conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of NTLA-2001 in participants with ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10624232/

Lessons from the first-in-human in vivo CRISPR/Cas9 ... Study and results: The first-in-human in vivo CRISPR/Cas9 trial of TTR Gene editing by NTLA-2001 in patients with Transthyretin Amyloidosis and cardiomyopathy ...