Phase 2 Study of Nemolizumab for Skin Thickening in Adults with Systemic Sclerosis

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What is this study about?

Systemic sclerosis is a rare condition that causes the skin to become thick and hard and can affect internal organs such as the lungs and heart. The study is testing an investigational drug called nemolizumab, which is given as a small injection under the skin, compared with a matching placebo. The medication is being examined to see if it can improve the skin changes and be safe for long‑term use.

The purpose of the study is to determine whether the drug can reduce skin thickness and be tolerated well over an extended period.

Participants will receive either the study medication or placebo by injection regularly for about one year and may continue for up to three years if they choose to stay in the extension phase. During the study, doctors will check the skin using a tool called the modified Rodnan Skin Score, which rates how tight the skin feels, and will perform a breathing test known as forced vital capacity to monitor lung function. Routine check‑ups will also include simple safety measurements such as blood tests, vital signs, and questions about any side effects.

1 baseline visit (week 0)

the first appointment after joining the study includes collection of medical history, physical examination, and baseline measurements such as skin thickness using the modified roddan skin score and lung function testing.

blood samples are taken to assess laboratory values and to store for future analysis.

2 randomization and first injection

participants are assigned in a double‑blind manner to receive either nemolizumab 30 mg solution for injection or a matching placebo.

the study medication is administered by subcutaneous injection using a pre‑filled pen.

the injection schedule and exact frequency are defined by the study protocol but are not detailed in the provided information.

3 main treatment period (52‑week)

participants receive regular subcutaneous injections of the assigned study medication for a total of 52 weeks.

clinic visits are scheduled periodically to monitor safety, record any adverse events, and perform efficacy assessments such as the modified roddan skin score and forced vital capacity measurement.

blood samples are collected to measure nemolizumab serum concentrations and to detect anti‑drug antibodies.

4 primary efficacy assessment at week 52

at the end of the 52‑week period, the change from baseline in the modified roddan skin score is evaluated as the primary outcome.

secondary outcomes include changes in lung function, response according to the revised composite response index in systemic sclerosis, and safety evaluations.

5 continuation into extension period

participants who remain in the study continue receiving the same study medication for an additional 156 weeks.

the decision to continue is made according to the study protocol and participant consent.

6 extension treatment period (weeks 53‑208)

ongoing subcutaneous injections are administered throughout the 156‑week extension.

regular safety monitoring continues, including assessment of vital signs, laboratory tests, weight, and electrocardiogram findings.

additional blood samples are taken to continue monitoring nemolizumab levels and anti‑drug antibodies.

7 final study visit (week 208)

the study concludes after 208 weeks (52 weeks + 156 weeks).

final evaluations of skin thickness, lung function, safety data, and laboratory parameters are performed.

the study medication is discontinued and participants are provided with information about post‑study follow‑up.

Who Can Join the Study?

Be at least 18 years old (or meet the legal adult age in your country if it is higher).
Have a diagnosis of systemic sclerosis that meets the 2013 ACR/EULAR classification criteria (the standard guidelines doctors use to confirm this condition).
For diffuse cutaneous systemic sclerosis (DcSSc), have a Modified Rodnan Skin Score (mRSS) of 12 to 29 at both the screening visit and the start of the study; for limited cutaneous systemic sclerosis (LcSSc), have an mRSS of 8 or higher at both visits. (The mRSS is a simple test doctors use to measure how thick the skin is.)
Not have a positive anti‑centromere blood test if you have LcSSc (this test looks for a specific antibody that is not allowed in this group).
Have a disease duration that is:
- 5 years or less if you have DcSSc, or
- 2 years or less if you have LcSSc.
(Disease duration means the time since the first symptom that is not Raynaud’s phenomenon.)
Be taking any background medicines for at least 3 months before the study and keep them stable, which may include:
- Nintedanib (150 mg or less twice a day), and/or
- One of the following, but not both together:
  - Methotrexate (25 mg or less once a week), or
  - Mycophenolate (up to 3000 mg daily for MMF, up to 2160 mg daily for MPS or MPA).
(These are medications often used to treat this condition.)
If your disease started 18 months ago or less, you automatically meet the activity requirement. If it started more than 18 months ago, you must have at least two of the following seven signs:
- Two new areas of skin involvement in the past 6 months.
- An increase of 3 or more points in the mRSS in the past 6 months.
- One new area of skin involvement plus an increase of 2 or more points in the mRSS in the past 6 months.
- Evidence of tendon friction rub, arthritis, or tenosynovitis that cannot be explained by another cause.
- A high‑sensitivity CRP level of 0.6 mg/dL or higher (a blood test that shows inflammation) or an ESR of 28 mm/hr or higher (another inflammation test).
- Evidence of lung involvement called SSc‑ILD seen on a special chest scan (HRCT) or a positive anti‑topoisomerase I (anti‑Scl‑70) antibody test (≥20 U/mL).
- An mDAI score of 2.5 or higher (a score that measures overall disease activity).
(If your disease started more than 18 months ago, you must not have a positive anti‑RNA polymerase III antibody test.)
Use effective contraception or agree to abstain from sex if you could become pregnant (or have a partner who could become pregnant) during the study and for at least 12 weeks after the last dose. Emergency contraception (such as Plan B™) is not allowed as a regular method.
If you are a woman who cannot become pregnant, you must meet one of the following:
- No menstrual periods for at least 1 year for reasons not related to health problems; if you are under 60, a blood test showing a follicle‑stimulating hormone (FSH) level of 40 IU/L or higher confirms menopause (no test needed if you are over 60).
- Have had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at least 3 months before screening.
Sign the informed consent form and be willing and able to follow all study procedures, including using an electronic device for questionnaires.

Who Cannot Join the Study?

If a blood test shows you are positive for the anti‑centromere antibody (a specific protein marker) and you have limited‑type systemic sclerosis, you cannot join the study.
If a blood test shows you are positive for the anti‑RNA polymerase III antibody and your disease has lasted more than 18 months, you are excluded.
If your kidney function test called creatinine clearance is less than 30 ml/min, you cannot participate.
If you have a current infection with hepatitis B, hepatitis C, or HIV (shown by positive blood tests), you are not eligible.
If you have an active bacterial, viral, fungal, or any serious infection that required a hospital stay or IV antibiotics/antivirals within the past 4 weeks, or oral antibiotics within the past 2 weeks, you are excluded.
If you have a known primary immune system problem, have had a bone‑marrow transplant, or have received advanced cell therapies such as CAR‑T cell therapy, you cannot join.
If you have had any cancer or blood‑forming disease in the last 5 years, you are excluded, except for treated skin cancers (basal cell carcinoma, squamous cell carcinoma in situ, cervical carcinoma in situ) or treated actinic keratoses with no recurrence in the past 12 weeks.
If you have a history of alcohol or drug dependence, or any condition that might make it difficult for you to follow study rules, you are not eligible.
If you have any other medical problem—including significant lung disease, mental health condition, or abnormal lab results—that could put you at risk or affect the study’s results, you are excluded.
If you are taking, or are expected to take, any of the following medicines and cannot stop them: systemic steroids, anti‑malarial drugs, cyclosporine, tacrolimus, other calcineurin inhibitors, cyclophosphamide, chlorambucil, biologic agents, anti‑CD‑20 therapies, cell‑depleting therapies, total lymphoid radiation, thalidomide, intravenous immunoglobulin, antifibrotic agents, soluble guanylate‑cyclase modulators, JAK inhibitors, tyrosine‑kinase inhibitors, penicillamine, or any other investigational drug, you cannot participate.
You must not drink alcohol or use other substances while you are in the study.
If your lung function is very low—specifically, forced vital capacity (FVC) less than 50 % of the normal predicted value or diffusing capacity (DLCO) less than 40 % of normal—you are excluded. This also includes severe chronic obstructive pulmonary disease, severe asthma, recent serious lung infections, frequent lung infections, current smoking, other serious respiratory diseases, or being listed for a lung transplant within the next year.
If you have serious heart problems such as a dangerous irregular heartbeat needing treatment, advanced heart failure (New York Heart Association Class III‑IV), unstable chest pain (angina), uncontrolled high blood pressure, cor pulmonale (right‑heart failure due to lung disease), fluid around the heart (pericardial effusion), a heart attack in the past 6 months, or severe pulmonary hypertension (WHO Class III or higher), you cannot join.
If you have severe malabsorption requiring intravenous nutrition, a recent episode of scleroderma‑related kidney crisis (SRC) within 6 months, or chronic liver disease (any Child‑Pugh stage), you are excluded.
If you weigh less than 30 kg (about 66 lb) at screening, you cannot participate.
If you are pregnant, breastfeeding, planning to become pregnant, or not willing to use reliable birth control during the study, you are excluded.
If you have already been treated with the study drug nemolizumab, you cannot join.
If you have another primary rheumatic autoimmune disease such as rheumatoid arthritis, systemic lupus erythematosus, polymyositis, dermatomyositis, systemic vasculitis, Sjögren’s syndrome, anti‑synthetase syndrome, or mixed connective‑tissue disease, you are excluded.
If you have a condition that looks like systemic sclerosis but is actually something else—such as localized scleroderma (morphea), eosinophilic fasciitis, graft‑versus‑host disease with skin thickening, certain fibromucinous skin disorders, or skin disease caused by chemicals or drugs—you cannot participate.
If you have had a severe allergic reaction (including anaphylaxis) to any immunoglobulin product or to any ingredient in the study medication, you are excluded.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Linden Sp. z o.o. sp.k.	Cracow	Poland
Poliklinika Vlatka Cavka d.o.o.	Zagreb	Croatia
Centre Hospitalier Universitaire De Lille	Lille	France
Oncopole Claudius Regaud	Toulouse	France
Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Italy

Other Sites

Site Name	City	Country
University Multiprofile Hospital For Active Treatment Saint Georgi EAD	Plovdiv	Bulgaria
Uniwersytecki Szpital Kliniczny W Bialymstoku	Bialystok	Poland
Direction Centrale Du Service De Sante Des Armees	Toulon	France
Centre Hospitalier Le Mans	Le Mans	France
Centre Hospitalier Universitaire De Nice	Nice	France
Specijalna Bolnica Medico	Rijeka	Croatia
University Multiprofile Hospital For Active Treatment St. Ivan Rilski EAD	Sofia	Bulgaria
Centre Hospitalier Universitaire De Rennes	Rennes	France
Poliklinika Solmed d.o.o.	Zagreb	Croatia
Centrum Medyczne Plejady Magdalena Celinska Loewenhoff Michal Zolnowski sp.k.	Cracow	Poland
University General Hospital Of Heraklion	Heraklion	Greece
Hospital Universitario Basurto	Bilbao	Spain
Hospital Universitario Dr Peset Aleixandre	Valencia	Spain
Hospital Quironsalud Malaga	Malaga	Spain
Twoja Przychodnia Nowosolskie Centrum Medyczne Sp. z o.o.	Nowa Sol	Poland
Centrum Badawcze Panaceum Agnieszka Brzezicka Magdalena Lenkiewicz Sp. z o.o.	Malbork	Poland
University Multiprofile Hospital For Active Treatment Kaspela EOOD	Plovdiv	Bulgaria
Malopolskie Centrum Kliniczne	Cracow	Poland
Azienda Socio Sanitaria Territoriale Ovest Milanese	Legnano	Italy
NextHealth S.A.	Thessaloniki	Greece
Mniowapjc Iacytprkif Cogstlqg Ssgsulqq Swb z ocnn	Warsaw	Poland
Prci Tdjyr Hultkyly Ueaekuwvxxlb	Sabadell	Spain
Lvhax Gypxuog Hoxfwldu Op Aszyfj	Athens	Greece
Ibekcrlh dx Csymyvvjagyt Hcmoplnnowu Uhgstyquyvwqj dt Souul Enrzcwf (egnrheo	Saint Priest En Jarez	France
Hydxzvzl Vtkq dbwrinxs	Barcelona	Spain
Hbqfxbao Uzhvvebvknwph dp A Cdbqzx	A Coruna Galicia	Spain
Ccdwdq Haflutfhgkc Rwrkgvks Ugmfwincauimh Ds Tqkih	Tours	France
Almuknx Uiy Iwraz Do Risspe Ezmytf	Reggio Emilia	Italy
Ceegkp Hsbnzoojppr Rdydxpdh Dapbktrrgfeieg	Angers	France

Trial status

Country	Status	Recruitment Start
Bulgaria	Not yet recruiting	02.06.2026
Croatia	Not yet recruiting	02.06.2026
France	Not yet recruiting	02.06.2026
Greece	Not yet recruiting	02.06.2026
Italy	Not yet recruiting	02.06.2026
Poland	Not yet recruiting	02.06.2026
Spain	Not yet recruiting	02.06.2026

Trial locations

Investigated drugs:

Nemolizumab

Nemluvio is an injectable medicine that is given under the skin. In this study it is being tested to see if it can help reduce the thickening of the skin that occurs in adults with systemic sclerosis. The drug works by targeting a specific part of the immune system that is thought to contribute to the skin changes in this disease. Participants receive the medication over a 52‑week main treatment period, and the study continues to follow safety and long‑term effects for up to 156 weeks. The goal is to find out how well Nemluvio works and how safe it is for people with this condition.

Investigated diseases:

Systemic scleroderma

Systemic sclerosis – Systemic sclerosis is a long‑lasting condition that causes the skin to become tight and thick. It often starts with swelling of the fingers or hands and may spread to the arms, face, and other parts of the body. Over time, the skin changes can be accompanied by hardening of blood vessels and small organs. The disease can also affect internal organs such as the lungs, heart, and kidneys, usually developing gradually. Symptoms may increase in intensity before stabilizing, and the condition can vary from mild to more extensive involvement.

Trial ID:

2025-522294-11-00

Protocol code:

SPR207796

NCT ID:

NCT07047690

Trial Phase:

Therapeutic exploratory (Phase II)

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Phase 2 Study of Nemolizumab for Skin Thickening in Adults with Systemic Sclerosis

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?