About Clinical Trials
- A research study that explores a medical strategy, investigational treatment or device in human participants.
- All potential new treatments go through a set of clinical trial phases under controlled conditions.
- For most clinical research of an investigational treatment, there are four general phases.
- Phase 1 tests safety in humans by giving the treatment or drug to healthy volunteers.
- Phase 2 tests safety and effectiveness in patients living with the disease being studied.
- Phase 3 tests safety and confirms effectiveness in patients with the disease and studies a larger group of people than in a Phase 2 trial.
- Phase 4 tests the drug’s effect in various populations and any side effects associated with long-term use. These studies are typically conducted after a drug is approved.
- Early clinical trials include Phase 1 studies, which test safety, side effects and best dose of a new treatment or drug. In a Phase 2 trial, patients usually receive the highest dose of drug that did not cause harmful side effects in the Phase 1 portion.
- Upon completion of Phase 3, regulatory agencies – for example, the U.S. Food & Drug Administration (FDA) or the European Medicines Agency (EMA) – determine whether the treatment is safe and effective for use in patients.
- People may consider whether or not to participate in clinical trials for various reasons, including:
- Gaining early access to potential treatments being studied for safety and effectiveness
- Receiving additional expert medical care
- Contributing to medical research
- Potentially helping future generations of people
- Understanding the risks and potential benefits of an investigational therapy
- Talk to your doctor if you are interested in participating in a clinical trial.
- If you’d like to learn more about clinical trials, visit: https://www.fda.gov/patients/clinical-trials-what-patients-need-know.
- The main difference between rare disease clinical trials and clinical trials in larger patient populations, such as in patients with diabetes, is that the population for the specific rare disease is much smaller.
- There are many implications due to a smaller patient population.
- Generally, these trials are small in scope
- They tend to move quickly through the development stages
- There is a higher dependence on a larger percentage of patients known to have the disease to participate
- It is important for as many patients as possible who have the rare disease to participate in the clinical trial to produce data that shows the investigational therapy to be a safe and effective treatment.
- There are several individuals and groups that work to protect patients during clinical trials. These include the study sponsor, the clinical trial investigator, a patient’s treating physicians, the institution or hospital where an investigational treatment will be provided, Institutional Review Boards (IRBs) and Independent Ethics Committees (IECs) as applicable and appropriate regulatory authorities.
- An IRB in the U.S. or an IEC in Europe are independent groups that protect the rights and welfare of people who participate in clinical trials.
- The IRB/IEC monitors the rights, safety and well-being of all clinical trial participants, with special attention to trials which might enroll vulnerable participants. The IRB/IEC also provides opinions regarding ethical approval of the trial plans and design, modification of trial plans or termination of a trial. These groups review each ongoing clinical trial at least annually, including a review of all aspects of each trial, such as risks, investigator qualification, information given to trial participants and payments that are provided to participants.
- The regulatory agency (either the Food and Drug Administration, or FDA, in the U.S., or individual country health agencies in the EU) is also required to review and approve how a clinical trial is designed before it begins.
- Every participant globally is protected because clinical trial sponsors are required to closely monitor the safety of participants and report serious adverse events to the relevant ethics group(s), regulatory agency and all other investigators.
- Informed consent must be provided by each patient/caregiver/legal guardian before the patient can participate in a clinical trial. Informed consent can only be given after the patient/caregiver/legal guardian has received clear, easy-to-understand information about the clinical trial, including its potential benefits and risks of participating from the study investigator.
- The Institutional Review Board (IRB) in the U.S. or Independent Ethics Committee (IEC) in Europe review and approve the informed consent before it is provided to patients. The IRB/IEC establishes the criteria for providing informed consent, such as how much time the patient has to consider whether to consent to participating in a clinical trial. The investigator is responsible for reviewing the informed consent with each clinical trial participant and ensuring the participant understands the informed consent before deciding whether to participate in the clinical trial.
About Belcesiran (DCR-A1AT)
- Belcesiran is an investigational therapy that Dicerna™ is developing for the treatment of alpha-1 antitrypsin (AAT) deficiency-associated liver disease (AATLD).
- Belcesiran utilizes Dicerna’s GalXC™ technology, which harnesses the body’s natural biological pathways to silence or “turn off” disease-causing genes with a high degree of selectivity and specificity.
- Ribonucleic acid interference (RNAi) is a biological process designed to “stop” or “turn off” diseases by “silencing” the genes underlying these conditions.
- RNAi does not permanently alter genes. When the drug is no longer bioavailable (available to be absorbed and used by the body), the disease returns to its native state.
- Using the ribonucleic acid interference (RNAi) process, investigational therapies transport the medicine to the targeted cells where the disease-causing genes can be silenced.
- Our technology attaches a naturally occurring sugar molecule to the investigational therapy and uses this molecule to transport the investigational therapy to the targeted cells where the disease-causing gene exists.
- Once the investigational therapy makes it to the targeted cell it is expected to silence the disease-causing gene by turning it off.
- Subcutaneous means “under the skin.” A therapy that is administered subcutaneously is delivered in a syringe with a needle administered under the skin which then enters the bloodstream.
About the SHINE Program and the ESTRELLA Trial
- SHINE is Dicerna’s clinical development program for belcesiran (DCR-A1AT), an investigational therapy under development as a potential treatment for AATLD. SHINE currently includes a Phase 2 study called ESTRELLA to evaluate belcesiran.
- The ESTRELLA clinical trial is a Phase 2 multiple-dose study of belcesiran (DCR-A1AT) in individuals with alpha-1 antitrypsin (AAT) deficiency-associated liver disease (AATLD). For more information about ESTRELLA, visit: www.clinicaltrials.gov using the identifier NCT04764448.
- The primary objectives of the ESTRELLA trial are:
- Evaluate the safety and tolerability of multiple doses of belcesiran (DCR-A1AT) in individuals with alpha-1 antitrypsin (AAT) deficiency-associated liver disease (AATLD)
- Characterize the pharmacodynamics (changes in serum AAT protein concentrations over time) of belcesiran in individuals with AATLD
- Secondary objectives are:
- Characterize the pharmacokinetics, or how drugs move within the body, of belcesiran in the plasma and urine in adult HVs and patients with AAT liver disease
- Characterize the effect of belcesiran on AATLD evaluated by liver biopsy
- The ESTRELLA clinical trial is a randomized, placebo-controlled, double-blind study in patients with alpha-1 antitrypsin (AAT) deficiency-associated liver disease (AATLD).
- Randomized means that participants will be randomly assigned to receive either placebo or belcesiran (DCR-A1AT).
- Double-blind means neither the participants nor the investigators know which intervention (placebo or belcesiran) participants are receiving.
- Participants will receive multiple doses of belcesiran or placebo and will be followed after administration of the last dose.
- You may be eligible to participate in ESTRELLA if you:
- Are male or female, aged 18 to 70 years
- Have a confirmed diagnosis of alpha-1 antitrypsin (AAT) deficiency and AAT-associated liver disease (AATLD)
- Have been tobacco-free for at least 3 months and are willing to remain tobacco-free for the entire study
- Agree to undergo liver biopsies (at screening and after receiving the last dose of the study drug)
- Meet other study-specific criteria
- There are several reasons that patients with alpha-1 antitrypsin (AAT) deficiency-associated liver disease might not be eligible to participate in the ESTRELLA trial. Examples include (but are not limited to) if a person:
- Has a history of chronic liver disease from any cause other than AAT deficiency
- Has a history of gastrointestinal bleeding, hepatic encephalopathy (a condition that causes temporary worsening of brain function in people with advanced liver disease) or acute exacerbations of lung disease
7. If patients are not eligible for the clinical trial, can they still get access to the medication?
- Dicerna is only permitted to provide belcesiran (DCR-A1AT) investigational product to patients who are participating in clinical trial programs that have been approved by the appropriate regulatory authority.
- The safety of study participants is a priority for Dicerna, the sponsor of the study. Investigators conducting the SHINE clinical trial program will monitor for potential side effects of belcesiran and will report serious side effects to the appropriate regulatory agency for further review. Safety is the most important aspect of the clinical trial, and Dicerna will monitor all participants’ safety very closely.
- If a participant shows signs of a side effect or adverse event while being treated with belcesiran, the investigator will work with the study sponsor, Dicerna, fellow investigators and the appropriate regulatory authorities to understand why it occurred and determine the appropriate follow-up treatment. Participants can leave the clinical trial at any time.
- Report adverse events and other side effects experienced during the trial by contacting EMEAAsiaSafetyCentral.SM@ppdi.com or 877-717-DRNA (3762).
- No, there is no cost to the patient to participate in this study.
- For a complete list of clinical trial locations for the ESTRELLA study, please email medicalinfo@dicerna.com.
- Dicerna is dedicated to helping individuals who live far away from trial sites by covering transportation and lodging expenses. Our reimbursement plans include travel, meals, lodging and stipend based on a set of requirements and financial/medical needs. Contact medicalinfo@dicerna.com to learn more about reimbursement.
- The trial is sponsored by Dicerna Pharmaceuticals, Inc. For more information, visit dicerna.com.
- To learn more about the clinical trial, please visit clinicaltrials.gov using the identifier NCT04764448 or email medicalinfo@dicerna.com.
About Dicerna
- Dicerna Pharmaceuticals, Inc., is a biopharmaceutical company focused on the discovery and development of innovative ribonucleic acid interference (RNAi)-based therapeutics for cardiometabolic, viral, chronic liver and complement-mediated diseases, as well as neurodegenerative diseases and pain.
- Dicerna is headquartered in Lexington, Mass. (USA).
- To learn more about Dicerna and its pipeline, management team and recent news, please visit dicerna.com.
