Understanding Clinical Studies:

advancing knowledge through research

Clinical studies are a type of medical research designed to better understand a disease. They can also explore different ways to treat a health condition, including developing new medicines that aren’t currently available.

There are two main types of clinical studies:

Clinical trials (also known as interventional studies)

Researchers test a specific intervention, such as a new medicine, according to a detailed research plan. Health regulators, like the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA), approve these plans and oversee the development of new medicines.

New medicines being tested in clinical trials are considered “investigational” only. During a series of trials, researchers monitor the safety and effectiveness of the medicine and compare results among the participants.

Observational studies

Researchers monitor individuals in their usual environment, without changing their activities, and track specific health information. For example, researchers want to learn more about the impact of sleep on overall health. Their study might look at individuals who sleep more than 6 hours a night compared to those who sleep less than 6 hours a night. The researchers would monitor any changes in overall health between these two groups.

During observational studies, researchers do not give investigational treatments to participants.

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The four phases of a clinical trial

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Participating in clinical studies

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Rhythm Pharmaceuticals clinical studies

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Common clinical study questions

The four phases of a clinical trial

There are typically four phases of clinical trials during the drug development process. These trials evaluate the safety and effectiveness of a potential medicine. Each phase can take months, sometimes years, and must be successfully completed before moving to the next phase. 

After all the phases are complete, even more time is spent compiling and reviewing the data. Most companies start with thousands of potential medicines, but very few make it to Phase 1 and even fewer get approved.

Phase 1: SAFETY

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Researchers test a medicine in a small group of “normal, healthy human volunteers,” meaning they do not have the condition the medicine is designed to treat. These tests evaluate safety, potential side effects, and the most appropriate amount of medicine to take.

DURATION

several months

Phase 2: MEDICAL CONCEPT TESTING

The medicine is given to a larger group of individuals who have the condition the medicine is intended to treat. During this phase, researchers try to get “proof” that the medicine could work, also known as “proof of concept.” This phase further evaluates safety, the most appropriate amount of medicine to take, and early data about how well the medicine may work.

DURATION

several months to 2 years

Phase 3: SAFETY + EFFECTIVENESS

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This phase expands to include a larger number of individuals who have the condition the medicine is intended to treat. Researchers continue to monitor the medicine’s effectiveness; compare it to standard, similar, or
placebo
treatments (if appropriate); and collect information about possible side effects.
This phase expands to include a larger number of individuals who have the condition the medicine is intended to treat. Researchers continue to monitor the medicine’s effectiveness; compare it to standard, similar, or
placebo
treatments (if appropriate); and collect information about possible side effects.

This phase expands to include a larger number of individuals who have the condition the medicine is intended to treat. Researchers continue to monitor the medicine’s effectiveness; compare it to standard, similar, or placebo treatments (if appropriate); and collect information about possible side effects.

DURATION

1 to 4 years

Phase 4: ADDITIONAL MONITORING

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After the treatment has been approved, researchers may continue to track it to gather more information about the medicine’s safety, benefits, and most appropriate use.

DURATION

varies

Throughout this clinical trial process, the sponsor works with health authorities, like the U.S. Food and Drug Administration 

(FDA) or the European Medicines Agency (EMA), to share data and information from its trials. These health authorities will decide if a medicine can be approved for use, based on the results of the trials. Approval of a medicine in one country does not mean that it is approved for use in another.

Most often, medicines are approved after a Phase 3 trial shows positive results. For this reason, Phase 3 trials are often referred to as “pivotal trials.”

The reality of experiments

Not all medicines are approved for use, or even make it to Phase 3. Clinical trials are basically an experiment, and events or findings along the way can impact the development process. For example, not recruiting participants in time may delay the overall timing of the trial.

Other challenges that could slow or stop a trial completely include: unexpected negative safety findings, results that show a medicine doesn’t really work, or inconsistent quality manufacturing of the medicine.

Although the drug development process can be unpredictable, it helps both science and medicine advance.

Participating in clinical studies

Eligibility

Each clinical study outlines specific requirements, called the “eligibility criteria,” to determine who is able to participate.

Eligibility criteria can include factors such as age, gender, type and stage of a disease, and medical history. Factors that allow an individual to participate are called inclusion criteria; factors that disqualify an individual from participating are called exclusion criteria.

A trial doctor, known as an investigator, determines who is eligible to participate in the study.

Participation considerations

The reasons individuals may decide to join a trial vary greatly, as this is a personal choice that must be carefully considered prior to participation. For example, they might join to gain access to a specialist or to a new medicine. They might also join to actively participate in medical and scientific research. Other considerations include frequency of appointments or potential travel required.

It’s important to note that investigational treatment involves some risk. Researchers closely monitor participants for safety, but not all of the effects are known.

Enrollment process

enrollment-icon

The first step when considering enrollment in a clinical trial is a conversation between the potential participant and his or her doctor to discuss the appropriateness of the trial and address any questions. If the trial is appropriate, screening sites can then determine whether the individual is eligible.

Rhythm Pharmaceuticals clinical studies

Talk with your doctor to learn more about these trials and determine if you may be eligible to participate.

Clinical trials

Each of the below studies evaluates the use of setmelanotide in individuals with rare genetic disorders of obesity.

LEPR deficiency obesity

Setmelanotide for the treatment of LEPR deficiency obesity

IN INDIVIDUALS WITH

  • LEPR deficiency obesity
    (early onset)

IN INDIVIDUALS WITH

⋅  LEPR deficiency obesity
(early onset)

STATUS
Active/not recruiting

clinicaltrials.gov locator
NCT03287960

Bardet-Biedl syndrome, Alström syndrome

Setmelanotide (RM-493), melanocortin-4 receptor (MC4R) agonist, in Bardet-Biedl syndrome (BBS) and Alström syndrome (AS) patients with moderate to severe obesity

IN INDIVIDUALS WITH

  • Bardet-Biedl syndrome with moderate to severe obesity
  • Alström syndrome with moderate to severe obesity

IN INDIVIDUALS WITH

⋅  Bardet-Biedl syndrome with moderate to severe obesity

⋅  Alström syndrome with moderate to severe obesity

STATUS
Active/not recruiting

clinicaltrials.gov locator
NCT03746522

POMC deficiency obesity

Setmelanotide for the treatment of early-onset POMC deficiency obesity

IN INDIVIDUALS WITH

  • POMC deficiency obesity (early onset)

IN INDIVIDUALS WITH

⋅  POMC deficiency obesity (early onset)

STATUS
Active/not recruiting

clinicaltrials.gov locator
NCT02896192

Multiple rare genetic disorders of obesity

Long-term extension trial of setmelanotide

IN INDIVIDUALS WITH 

  • Rare genetic disorders of obesity who previously participated in an interventional trial for setmelanotide

IN INDIVIDUALS WITH 

⋅  Rare genetic disorders of obesity who previously participated in an interventional trial for setmelanotide

STATUS
Active/recruiting

clinicaltrials.gov locator
NCT03651765

Multiple rare genetic disorders of obesity

Setmelanotide Phase 2 treatment trial in patients with rare genetic disorders of obesity

IN INDIVIDUALS WITH

  • Heterozygous POMC, PCSK1, or LEPR gene variants
  • POMC deficiency obesity
  • LEPR deficiency obesity
  • Smith-Magenis syndrome
  • SH2B1 deficiency obesity (including 16p11.2 deletions)
  • Leptin deficiency obesity with
    loss of response to leptin
    replacement therapy (i.e.
    metreleptin)
  • SRC1 deficiency obesity
  • MC4R deficiency obesity

IN INDIVIDUALS WITH

⋅  Heterozygous POMC, PCSK1, or LEPR gene variants

⋅  POMC deficiency obesity

⋅  LEPR deficiency obesity

⋅  Smith-Magenis syndrome

⋅  SH2B1 deficiency obesity (including 16p11.2 deletions)

⋅  Leptin deficiency obesity with
loss of response to leptin
replacement therapy (i.e.
metreleptin)

⋅  SRC1 deficiency obesity

⋅  MC4R deficiency obesity

STATUS
Active/recruiting

clinicaltrials.gov locator
NCT03013543

Observational studies

Each of the below studies aims to better understand rare genetic disorders of obesity without a therapeutic intervention.

GO-ID

Genetic testing and phenotypic characterization of severely obese pediatric and adult volunteers

IN INDIVIDUALS WITH

  • Severe obesity (both children and adults)

IN INDIVIDUALS WITH

⋅  Severe obesity (both children and adults)

STUDY OBJECTIVE
Identify individuals with a rare genetic cause of obesity via screening

STATUS
Active/not recruiting

clinicaltrials.gov locator
NCT02849977

Natural history

An observational, prospective natural history study of early-onset extreme obesity due to bi-allelic loss-of-function mutations in the POMC, PCSK1 or LEPR genes (NHS)

IN INDIVIDUALS WITH

Bi-allelic loss-of-function genetic variation resulting in:

  • POMC deficiency obesity
  • PCSK1 deficiency obesity
  • LEPR deficiency obesity

IN INDIVIDUALS WITH

Bi-allelic loss-of-function genetic variation resulting in:

⋅  POMC deficiency obesity

⋅  PCSK1 deficiency obesity

⋅  LEPR deficiency obesity

STUDY OBJECTIVE
Collect information from people with early-onset extreme obesity due to specific genetic variations

STATUS
Active/recruiting

clinicaltrials.gov locator
NCT03621007

TEMPO

The TEMPO (tracing the effect of the MC4 pathway in obesity) registry

IN INDIVIDUALS WITH

  • MC4R-pathway genetic obesity

IN INDIVIDUALS WITH

⋅  MC4R-pathway genetic obesity

STUDY OBJECTIVE
Develop a registry of individuals to try to better understand the impact of the MC4R pathway in obesity

STATUS
Active/not recruiting

clinicaltrials.gov locator
NCT03479437

LEPR, leptin receptor; MC4R, melanocortin-4 receptor; PCSK1, proprotein convertase subtilisin/kexin type 1; POMC, proopiomelanocortin

Common clinical study questions

What is informed consent?

Before an individual agrees to participate in a trial, he or she must complete an informed consent document. This means that researchers have provided the participant with key facts about the trial, including required procedures and frequency, potential effects of the medicine, and contact information. Signing this document shows that the individual understands the study and agrees to participate.

What is a protocol?

Every clinical trial must follow a detailed plan, called a “protocol”. The protocol outlines the study rationale, objectives, and design, and is strictly monitored for adherence to scientific and ethical standards. It includes information about participation criteria, study length, treatment dosage, and any required procedures.

What is a placebo?

A placebo is a substance that has no effect. It usually comes in the same form as the medicine that is being tested, but does not contain any medicine. Placebos can be used in studies to examine the effectiveness of a medicine by comparing results between individuals who received the medicine and those who received the placebo.

What is expanded access?

Sometimes also called “compassionate use” or “early access,” expanded access is a way to gain access to an investigational medical treatment when no alternative therapy options are available. This approach typically applies only to individuals with an immediately life-threatening condition or serious disease or condition, and when enrollment in a clinical trial is not possible. With expanded access, no comparable or satisfactory treatment is available, the potential benefit must outweigh the treatment risk, and taking the investigational treatment must not interfere with the development or approval of the medicine.

It’s important to know that expanded access is not offered for all medicines. Companies often include specific policy details on their websites. Rhythm’s expanded access policy is available here.

How much does it cost to participate?

Although every trial is different, participation is usually free. The sponsor of the trial usually pays for doctor visits and medicine; travel expenses are also usually covered. You should always check with your doctor and the trial sponsor to understand costs for which you could be responsible.

Can participants leave a trial after it begins?

Yes. Participating in the research study is optional. It is on a volunteer basis and individuals can choose to withdraw their participation at any time.

Whom do I contact for more information?

For information about a clinical trial that could be a good fit for you, speak with your doctor as a first step. Ask your doctor to email clinicaltrials@rhythm.jpa.com for more information about the Rhythm clinical trials. For patient resources or other questions, contact patientadvocacy@rhythm.jpa.com.