FAQ

• A research study that explores whether a medical strategy, investigational medicine, or device is safe and effective for humans.

• All potential new treatments go through a set of clinical trial phases under controlled conditions.
• There are 4 phases of clinical research.
  • 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 the Phase 2 trial.
  • Phase 4 tests the drug's effect in various populations and any side effects associated with long-term use after it is approved.
• Regulatory agencies – for example, the U.S. Food & Drug Administration (FDA) or the European Medicines Agency (EMA) – determine whether the treatment can be prescribed by physicians to patients.

People choose whether or not to participate in clinical trials for various reasons, including:

• Gaining early access to investigational medication
• Contributing to medical research
• Potentially helping future generations of patients diagnosed with primary hyperoxaluria

Talk to your doctor if you are interested in participating in a clinical trial.

• The main difference between rare disease clinical trials and clinical trials in larger patient populations, such as 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 more quickly through the development stages
  • There is a higher dependence on a larger percentage of patients to participate
• It’s important for as many patients as possible to participate due to the low number of patients in the entire population.

• An independent group called an Institutional Review Board (IRB) in the United States or an Independent Ethics Committee (IEC) in Europe protects the rights and welfare of people who participate in clinical trials.
• The IRB/IEC monitors the ethical aspects, progress and results of the clinical trial from start to finish.
• The regulatory agency (either the Food and Drug Administration [FDA] in the U.S., or individual country health agencies in the EU and other territories) are also required to review and approve how a clinical trial is designed before it begins.

• Informed consent is when the patient/caregiver/legal guardian is provided clear, easy-to-understand information as he/she is deciding whether to participate in a clinical trial.
• Both the Institutional Review Board (IRB) and International Ethics Committee (IEC) and the regulatory agency ensure that each clinical trial participant receives and understands the informed consent in order to make the most informed decision.

• Nedosiran is an investigational therapy that Dicerna is developing for the treatment of all known forms of primary hyperoxaluria (PH).
• Nedosiran utilizes Dicerna’s GalXC^TM RNAi technology, which harnesses the body’s natural biological pathways to silence or “turn off” disease-driving genes with a high degree of selectivity and specificity.

• Ribonucleic acid interference (RNAi) is a natural process that occurs within the human body at the molecular level. Its function is to silence, or “turn off,” specific genes that cause disease.
• RNAi is not gene therapy or gene editing and does not result in permanent alteration of genes. RNAi therapies are fully reversible after cessation of treatment and can also be modulated by dose or intervals between administration, unlike gene therapy or gene editing.

• Using RNAi, investigational therapies need a delivery system to transport the medicine to the liver cells, thus silencing their disease-driving genes.
• Dicerna attaches a specialized type of sugar molecule to the investigational therapy and uses the sugar molecule as the delivery system to send the intended therapy to the correct target.
• Once the therapy makes it to the correct target, then the therapy silences the disease-driving gene by turning it off.

• Subcutaneous means “under the skin.” So, a therapy that is delivered subcutaneously is delivered with a needle under the skin before it enters the bloodstream.

• Learn more about the clinical trials by contacting Dicerna at medicalinfo@dicerna.com, or by visiting www.clinicaltrials.gov and entering the NCT identifier number for the appropriate study.
  PHYOX7: NCT04580420
  PHYOX8: NCT05001269
  PHYOX-OBX: NCT04542590

• Dicerna, the sponsor of the PHYOX^TM program, believes that the best way for patients with primary hyperoxaluria (PH) to receive access to investigational treatments before they are approved is for those patients to participate in clinical trials. In some extreme circumstances when this is not possible, patients with life-threatening diseases or conditions may seek special access to investigational medicines outside of a clinical trial setting. These situations are typically referred to as compassionate use, but can also be known as expanded access, early access, pre-approval access and emergency use.

• The safety of study participants is a priority for Dicerna, the sponsor of the study. Researchers will monitor for potential side effects of nedosiran and will report serious side effects to the Institutional Review Board (IRB) 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 nedosiran, the researcher will investigate why it occurred and prescribe the appropriate clinical treatment. Participants can leave the clinical trial at any time.

• No, there is no cost to participate in a PHYOX^TM study.

• For a complete list of clinical trial locations for the PHYOX^TM studies, please contact Dicerna at medicalinfo@dicerna.com, or visit www.clinicaltrials.gov and enter the identifier number for the appropriate study (see below) into the search bar. You may also submit your information through the forms found on the PHYOX7, PHYOX8, and PHYOX-OBX study pages.
  PHYOX7: NCT04580420
  PHYOX8: NCT05001269
  PHYOX-OBX: NCT04542590

• 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 your study center to learn more about reimbursement and travel agencies.

• The trials are sponsored by Dicerna Pharmaceuticals, Inc., a Novo Nordisk company. For more information, visit Dicerna’s website.