A Multicenter, Randomized, Double-blind, Placebo Controlled, Parallel-group Trial to Investigate the Efficacy and Safety of Different Intra Articular (i.a.) Dosages of Sprifermin in Subjects With Primary Osteoarthritis of the Knee

This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase 2 trial of Sprifermin administered intra-articularly in participants with primary osteoarthritis of the knee and Kellgren-Lawrence Grade 2 or 3. The trial was intended to investigate the efficacy and safety of different intra articular dosages of Sprifermin in these individuals.

Start Date29 Jul 2013

Sponsor / Collaborator

EMD Serono Research & Development Institute, Inc.

[+1]

NCT01689337

/ TerminatedPhase 2

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase II Trial to Investigate the Efficacy and Safety of 30 mcg and 100 mcg AS902330 Given as One Cycle of Three Intra-articular Knee Injections Once a Week for Three Weeks as an Adjunct Treatment to Patients Following Microfracture Surgery for Cartilage Injury of the Knee.

This is a Phase 2, double-blind, multicenter, randomized, placebo-controlled trial to evaluate the efficacy and safety of Sprifermin (AS902330) (recombinant human fibroblast growth factor-18 [rhFGF-18]) as an adjunct treatment to subjects following microfracture (MFx) surgery for cartilage injury of the knee.
Primary Objectives
* To evaluate the effect of Sprifermin (AS902330) intra-articular knee injections as adjunct to microfracture (MFx) surgery on the composition of the refilled cartilage in the target knee, as measured by gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) time constant 1 (T1) relaxation time at 6 months after MFx surgery
* To evaluate the safety profile of Sprifermin (AS902330) when administered intra-articular into the knee as adjunct to MFx surgery in subjects with cartilage injury of the knee
Secondary Objectives
* To further support the efficacy and safety of Sprifermin (AS902330) as an adjunct to MFx for cartilage injury repair through symptomatic outcomes and quantitative MRI measurement

Start Date01 Apr 2013

Sponsor / Collaborator

EMD Serono, Inc.

NCT01066871

/ TerminatedPhase 2

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Phase II Trial to Investigate the Efficacy and Safety of Weekly Intra-articular (i.a.) Injections of 10, 30, and 100 µg of AS902330 for Three Consecutive Weeks in Patients With Acute Cartilage Injury of the Knee

Several people all over the world suffer from cartilage injuries in the knee. Symptoms include pain, joint swelling, and loss of function. Without repair, cartilage injury may ultimately lead to osteoarthritis (OA). Natural healing is poor, and to date treatment is available only for deep cartilage defects involving also the underlying bone. A promising candidate for drug treatment of cartilage injury is sprifermin (AS902330), a recombinant form of the human fibroblast growth factor (FGF) 18.
So far, the drug has been used in subjects with different stages of knee OA in two ongoing studies without emerging safety issues following single and multiple intra-articular injections of ascending doses. However, OA represents late-stage cartilage injury, where repair might be difficult due to diffuse damage, reduced responsiveness of the cartilage, and/or the involvement of other joint structures.
This clinical trial is meant to provide the proof of concept and to identify an efficacious dose of sprifermin (AS902330) for the treatment of adult subjects with acute cartilage injuries of the knee. The first subject for this trial was treated on the 19th of April 2010.

Start Date01 Mar 2010

Sponsor / Collaborator

Merck KGaA

100 Clinical Results associated with Sprifermin

100 Translational Medicine associated with Sprifermin

100 Patents (Medical) associated with Sprifermin

Literatures (Medical) associated with Sprifermin

01 Mar 2025·OSTEOARTHRITIS AND CARTILAGE

Exploring a novel outcome measure of symptom progression in knee osteoarthritis utilizing a large randomized trial

Article

Author: Somberg, Kenneth ; Conaghan, Philip G ; Guermazi, Ali ; Katz, Nathaniel ; Clive, Julia ; Goel, Niti ; Hochberg, Marc C ; Hunter, David J ; Johnson, Mary ; Knight, Chris ; Zhao, Luping

OBJECTIVES:

Explore a newly defined composite measure of symptom progression for knee osteoarthritis (KOA) in a large, randomized study of a potential disease-modifying osteoarthritis drug (DMOAD).

DESIGN:

Using longitudinal KOA studies, a potential composite endpoint of time to symptom progression was defined as the first occurrence of worsening of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain of ≥10 points with no improvement (≤9 point decrease) in WOMAC Function (0-100 scale). A post hoc analysis explored discrimination and association with structural outcomes in the sprifermin FORWARD trial through Years 3 and 5. All treatment arms of the intent-to-treat population were analyzed.

RESULTS:

Among the 549 FORWARD participants, 442 (80.5%) completed Year 3, and 378 (68.9%) completed Year 5. Sprifermin showed dose-dependent benefits in the time to symptom progression at Year 3 with hazard ratio (95% CI) for each sprifermin treatment arm vs placebo as follows: 100 μg every 6 months (Q6M), 0.51 (0.28, 0.93); 100 μg Q12M, 0.69 (0.40, 1.20); 30 μg Q6M, 0.89 (0.53, 1.50); and 30 μg Q12M, 0.80 (0.47, 1.35). Similar findings were seen through Year 5 and for a subgroup based on modern clinical trial inclusion criteria. There were increased numbers of knee replacements in symptom progressors (n=8, 5.6%) vs non-progressors (n=7, 1.7%).

CONCLUSIONS:

The symptom progression endpoint discriminated between placebo and treatment responses in a post hoc analysis of a Phase 2 investigational DMOAD KOA trial. The endpoint requires validation and further exploration in DMOAD clinical trials.

TRIAL NUMBER:

NCT01919164.

01 Dec 2024·Osteoarthritis and cartilage open

Unbiased analysis of knee cartilage thickness change over three years after sprifermin vs. placebo treatment – A post-hoc analysis from the phase 2B FORWARD study

Article

Author: Somberg, Kenneth ; Maschek, Susanne ; Ladel, Christoph ; Bihlet, Asger Reinstrup ; Zhao, Luping ; Wirth, Wolfgang ; Knight, Chris ; Eckstein, Felix

Objective:

Post-treatment cartilage morphometry in the FORWARD study was performed without blinding to MRI acquisition order, involving potential reader bias. Here we obtained unbiased estimates of cartilage change post-treatment, reading year (Y)2 and Y5 MRIs with blinding to time point. We studied whether post-treatment cartilage thickness change differed between sprifermin- and placebo-treated knees.

Methods:

FORWARD was a 5-year randomized control trial in 549 knee osteoarthritis patients. Here, Y2/Y5 images were analyzed with blinding to relative temporal order and treatment group. Cartilage change during Y2→Y5 was obtained in 337 participants: n = 57 treated with placebo intra-articular injections every 6 months (q6M); n = 69 with 30 μg sprifermin every 12 months (q12 M), n = 67 with 30 μg q6M, n = 73 with 100 μg q12 M, and n = 71 with 100 μg q6M between baseline (BL) and 18 M. Total femorotibial joint (TFTJ) cartilage thickness was the primary analytic focus.

Results:

TFTJ cartilage thickness change during Y2→Y5 was -26μm (SD64; 95%CI -32,-19) across the cohort; no statistically significant difference (p = 0.80) was observed between Sprifermin treated or placebo arms (one-way ANOVA). All groups lost cartilage, but the treatment-related difference in cartilage thickness in Sprifermin arms relative to placebo at Y2 was maintained until Y5. Annualized cartilage change in placebo participants was -8.2 μm (SD21; 95%CI -14,-2.5) during Y2→Y5 vs. -5.4 μm (SD27; 95%CI -13,1.8) during BL→Y2; no significant difference was identified (t-test).

Conclusion:

FORWARD is the first study evaluating post-treatment benefits of a potential disease modifying osteoarthritis drug. Cartilage thickness gained with 100 μg sprifermin at Y2 is maintained to Y5 and thus appears viable and sustainable.This is a post-hoc analysis of the FORWARD trial: ClinicalTrials.gov Identifier: NCT01919164.

01 Oct 2024·OSTEOARTHRITIS AND CARTILAGE

Is detection of disease-modifying osteoarthritis drug treatment more effective when performing cartilage morphometry without blinding to MR image acquisition order?

Article

Author: Somberg, Kenneth ; Maschek, Susanne ; Wisser, Anna ; Ladel, Christoph ; Bihlet, Asger Reinstrup ; Zhao, Luping ; Wirth, Wolfgang ; Eckstein, Felix ; Knight, Chris

OBJECTIVE:

We here explore whether observed treatment effects of a putative disease-modifying osteoarthritis drug (DMOAD) are greater when cartilage morphometry is performed with rather than without knowledge of magnetic resonance imaging (MRI) acquisition order (unblinded/blinded to time point).

METHODS:

In the FORWARD (FGF-18 Osteoarthritis Randomized Controlled Trial with Administration of Repeated Doses) randomized controlled trial, 549 knee osteoarthritis patients were randomized 1:1:1:1:1 to three once-weekly intra-articular injections of placebo, 30 µg sprifermin every 6 or 12 months (M), or 100 µg every 6/12 M. After year 2, cartilage segmentation of BL through 24 M MRIs was performed, with blinding to acquisition order. After year 5, 24 and 60 M MRIs were analyzed together, with unknown relative order, but with segmented BL images as reference (24 M unblinded vs. BL), by the same operators. Total femorotibial joint cartilage thickness (TFTJ_ThC) change was obtained for 352 participants analyzed under both conditions.

RESULTS:

Twenty-four-month data read unblinded to order revealed a -35 ± 44 µm lower TFTJ_ThC than blinded analysis (all groups: lower/upper bounds -120/+51 µm; correlation r² = 97%). With unblinded analysis, the placebo group lost -46 ± 57 µm TFTJ_ThC over 24 M, whereas 100 µg/every 6 M lost -2.2 ± 73 µm (difference =44 µm [95% CI: 22, 66]). With blinded analysis, placebo lost -11 ± 53 µm, whereas 100 µg/every 6 M gained 30 ± 62 µm (difference = 40 µm [95% CI: 21, 60]). 100 µg sprifermin injected every 6 M showed statistically significant (p < 0.001) treatment effects on TFTJ_ThC, with Cohen D = -0.66 for unblinded and D = -0.69 for blinded analysis.

CONCLUSIONS:

These results do not reveal that detection of proposed DMOAD treatment is enhanced with MRIs read unblinded to order; rather, the sensitivity is similar to blinded analysis. Choices on blinded vs. unblinded analysis may thus be based on other criteria.

News (Medical) associated with Sprifermin

26 Jun 2024

·www.fiercebiotech.com

AI-focused Formation secures Sanofi-backed $372M series D to license more drugs

Formation Bio said it plans to deploy new capital to continue to acquire and in-license clinical-stage assets from its biotech and pharma partners. Megarounds have been few and far between in 2024, but Formation Bio has managed to draw in an impressive $372 million series D as the AI-focused biotech seeks to expand its pipeline. AI companies like to promise the world, but Formation’s offering is more mundane. The idea is that Formation will partner with biotechs to improve their workflow automation—such as generating tailored patient recruitment content for specific cohorts of a clinical trial or speedily producing AI-generated adverse event reports. The ambition accelerates when the company looks ahead to the “medium term,” when it hopes to assemble a so-called “AI R&D Scientist” that can “provide drug development teams with decision support and eventually steer high-quality R&D decisions.” “In the long term, the company's goal is to build and train AI models that can better predict toxicity, tolerability, and one day, efficacy,” Formation explained in a June 26 release. The series D was led by a16z with “significant participation” from existing partner Sanofi—which has other AI-focused collaborations with partners including the likes of Owkin and Exscientia. Formation, which was formerly known as TrialSpark, said it plans to deploy this capital to continue to acquire and in-license clinical-stage assets from its biotech and pharma partners. The company currently lists three candidates in its clinical pipeline, including a SYK/JAK inhibitor called gusacitinib in phase 3 development for chronic hand eczema. There’s also a sodium channel blocker called ASN008 in phase 2 trials for notalgia paresthetica and itch associated with atopic dermatitis as well as an FGF18 drug called sprifermin in phase 2 for knee osteoarthritis. Both gusacitinib and ASN008 were bought from Asana BioSciences in 2022, while sprifermin was licensed from Merck KGaA. “By partnering with Formation Bio, smaller biotechs can advance more than just their lead asset, creating a pathway for other drugs in their pipeline,” the company said in the release. “For large pharma companies, Formation Bio creates an ‘off balance sheet’ pathway for development, enabling a company to take more shots on goal in a P&L efficient way.” Sanofi already announced a drug development partnership with both Formation and OpenAI last month. CEO Paul Hudson used a statement in this morning’s release to reemphasize that the French pharma is “all in on AI.” “We are proud to partner with and invest in Formation Bio, whose AI-driven drug development vision and capabilities will help lead our industry forward in the shared ambition to accelerate and improve how we bring more new medicines to patients,” Hudson added.

Phase 2Acquisition

31 Oct 2023

·www.sciencedaily.com

New hope to treat and reverse osteoarthritis

Current osteoarthritis treatment manages symptoms rather than addressing the underlying disease, but a new study has shown the condition may be treatable and reversible. Current osteoarthritis treatment manages symptoms rather than addressing the underlying disease, but a new University of Adelaide study has shown the condition may be treatable and reversible. Osteoarthritis is the degeneration of cartilage and other tissues in joints and is the most common form of arthritis in Australia, with one in five people over the age of 45 having the condition. It is a long-term and progressive condition which affects people's mobility and has historically had no cure. Its treatment cost the Australian health system an estimated $3.9 billion in 2019-20. Often described as a 'wear and tear' condition, factors such as ageing, obesity, injury and family history contribute to the progression of osteoarthritis. University of Adelaide researchers discovered a novel population of stem cells -- marked by the Gremlin 1 gene -- responsible for the progression of osteoarthritis. Treatment with fibroblast growth factor 18 (FGF18) stimulated the proliferation of Gremlin 1 cells in joint cartilage in mice, leading to significant recovery of cartilage thickness and reduced osteoarthritis. Gremlin 1 cells present opportunities for cartilage regeneration and their discovery will have relevance to other forms of cartilage injury and disease, which are notoriously challenging to repair and treat. It challenges the categorisation of osteoarthritis as wear and tear. "The findings of our study reimagine osteoarthritis not as a 'wear and tear' condition but as an active, and pharmaceutically reversible loss of critical articular cartilage stem cells," said the University of Adelaide's Dr Jia Ng from the Adelaide Medical School, who co-led the study. "With this new information, we are now able to explore pharmaceutical options to directly target the stem cell population that is responsible for the development of articular cartilage and progression of osteoarthritis." While Dr Ng describes current treatments for osteoarthritis as a "Band-Aid approach," this new understanding could lead to a pharmaceutical treatment that reverses osteoarthritis and helps to address health outcomes associated with the disease. "Known comorbidities of osteoarthritis include heart, pulmonary, and kidney disease, mental and behavioural conditions, diabetes, and cancer," said Dr Ng. "Our study suggests that there may be new ways to treat the disease rather than just the symptoms, leading to better health outcomes and quality of life for people who suffer from osteoarthritis." Though this discovery is limited to animal models, Dr Ng said there are genetic similarities to human samples, and human trials are ongoing. "We look forward to the outcome of these trials and to contribute to the better understanding of a pharmaceutical mechanism to treat osteoarthritis," she said. Results of a five-year clinical trial study using FGF18, known clinically as Sprifermin, were published in 2021 with potential long-term clinical benefit and no safety concerns. Phase 3 of the Sprifermin trial is ongoing, and researchers envision public access to this treatment soon.

Phase 3

23 May 2023

·www.prnewswire.com

TrialSpark Announces First Patient Dosed in Phase 2 Clinical Trial for ASN008-201 in Atopic Dermatitis

NEW YORK, May 23, 2023 /PRNewswire/ -- TrialSpark, Inc. announced today that the first patient has been dosed in its Phase 2 clinical trial for ASN008-201, a topical sodium channel blocker in development for pruritus associated with atopic dermatitis (AD). This clinical trial is a randomized, double-blind, vehicle-controlled, Phase 2 trial to evaluate the anti-pruritic efficacy, safety, tolerability, and pharmacokinetics of ASN008 in adults with mild to moderate AD (NCT05870865). Topline data for this trial is expected in 2024. Atopic dermatitis is a chronic inflammatory skin disease, and pruritus is the most burdensome and prevalent symptom in patients suffering from AD. Treating atopic itch, which impacts more than 16.5 million patients in the US, has historically been a challenge due to an incomplete understanding of the multiple mechanisms underlying its pathogenesis. "We are thrilled to have dosed our first patient in this clinical trial," said Gavin Corcoran, Chief Development Officer at TrialSpark. "Dermatology is a core focus area for our company, and there is enormous unmet patient need, so we're looking forward to progressing this clinical trial as efficiently as possible." This clinical trial will enroll approximately 120 participants at around 28 study sites across the United States. Eligible participants will be randomized in a 1:1:1:1 ratio to receive ASN008 gel 1.25%, ASN008 gel 2.5%, ASN008 gel 5%, or matching vehicle twice a day for 4 weeks (28 days), followed by a 4-week (28-day) follow-up period. "We are grateful to the patients who are participating in this clinical trial and to the healthcare professionals who are working with us to advance our research," said Benjamine Liu, TrialSpark CEO and Co-Founder. "Our company's mission is to bring new treatments to patients faster than ever before, and the contributions of patients, doctors, and sites are essential to achieving that goal." For more information about the clinical trial, please visit . About TrialSpark Founded in 2016, TrialSpark is a tech-driven pharma company differentiated by radically more efficient drug development. TrialSpark has built a technology platform that optimizes all aspects of clinical drug development, enabling more efficient trial design, faster trial completion, and higher quality trial data. The company acquires clinical-stage drugs from pharmaceutical and biotech companies and develops them faster, unlocking greater value per program and accelerating access to new treatments for patients. TrialSpark's current therapeutic areas of focus include rheumatology, dermatology, and cardiometabolic diseases. TrialSpark is actively growing its development pipeline. In November 2022, the company announced the formation of Libertas Bio following the acquisition of a majority position in a portfolio of immunodermatology assets from Asana BioSciences. The Libertas Bio pipeline includes ASN008, as well as global rights to gusacitinib, an oral Phase 3-ready dual JAK/SYK inhibitor in development for chronic hand eczema. TrialSpark also announced the formation of Highline Bio following the acquisition of worldwide rights to sprifermin - a potential first-in-class disease modifying treatment for osteoarthritis - from Merck KGaA, Darmstadt, Germany. Media Contact: [email protected] BD/Partnerships Contact: [email protected] SOURCE TrialSpark

Phase 2Acquisition

100 Deals associated with Sprifermin

External Link

KEGG	Wiki	ATC	Drug Bank
-	Sprifermin	-	DB12616

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Osteoarthritis, Knee	Phase 2	United States	EMD Serono Research & Development Institute, Inc.	29 Jul 2013
Osteoarthritis, Knee	Phase 2	Argentina	EMD Serono Research & Development Institute, Inc.	29 Jul 2013
Osteoarthritis, Knee	Phase 2	Czechia	EMD Serono Research & Development Institute, Inc.	29 Jul 2013
Osteoarthritis, Knee	Phase 2	Denmark	EMD Serono Research & Development Institute, Inc.	29 Jul 2013
Osteoarthritis, Knee	Phase 2	Estonia	EMD Serono Research & Development Institute, Inc.	29 Jul 2013
Osteoarthritis, Knee	Phase 2	Hong Kong	EMD Serono Research & Development Institute, Inc.	29 Jul 2013
Osteoarthritis, Knee	Phase 2	Poland	EMD Serono Research & Development Institute, Inc.	29 Jul 2013
Osteoarthritis, Knee	Phase 2	Romania	EMD Serono Research & Development Institute, Inc.	29 Jul 2013
Knee Injuries	Phase 2	-	EMD Serono, Inc.	01 Apr 2013
Cartilage Injury	Phase 2	Germany	Merck KGaA	01 Mar 2010

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01919164 (FORWARD, Pubmed \| Semin Arthritis Rheum)	Phase 2	Osteoarthritis, Knee	549	Sprifermin 100 µg q6mo	gzouecapgg(meblbpvzme) = kprstbaqmf dxfxsfcpca (iurxvgoldb, ( - 22.42, 4.92))	-	11 Mar 2021
				Sprifermin 100 µg q12mo	gzouecapgg(meblbpvzme) = gzsfcmqaoy dxfxsfcpca (iurxvgoldb, ( - 6.22, 8.16))
NCT01919164 (FORWARD, CTgov)	Phase 2	Osteoarthritis, Knee	549	Placebo (Placebo)	whhnlatcby(malimtitnp) = mgdpyqvoap tsnaaaognp (qlsraxqreu, 0.07) View more	-	13 Jul 2020
				Placebo+Sprifermin (Sprifermin (AS902330) 30 mcg/Placebo - 2 Cycles)	whhnlatcby(malimtitnp) = haxoquxdbx tsnaaaognp (qlsraxqreu, 0.07) View more
phase II clinical trial (EULAR2020)	Phase 2	Osteoarthritis PRO-C2 - \| huARGS \| FBN-C	-	Sprifermin	cwnymsegms(eawjbngskr) = ttvelalfim rnjnwfgqmj (pydomylovy ) View more	Positive	03 Jun 2020
				Placebo	cwnymsegms(eawjbngskr) = rwixygrdrs rnjnwfgqmj (pydomylovy ) View more
FORWARD study (EULAR2018)	Phase 2	Osteoarthritis, Knee	549	Sprifermin	habxjzrbol(crpntljkit) = zsfxsjiehd arxqewbvwr (ohmgptuhtt )	Positive	13 Jun 2018
NCT01066871 (CTgov)	Phase 2	Cartilage Injury	74	AS902330 (Sprifermin (AS902330) 10 mcg)	nmsjijyzdz(ybisispmmx) = hicwjhjmbj ttqlgtgyjl (fionuvhkrj, 27.17) View more	-	23 Mar 2016
				AS902330 (Sprifermin (AS902330) 30 mcg)	nmsjijyzdz(ybisispmmx) = swzzbixnbz ttqlgtgyjl (fionuvhkrj, 29.24) View more
NCT01033994 (Pubmed \| Arthritis Rheumatol)	Phase 1	-	168	Sprifermin 100 μg	jmcrxgodkc(gieuuqdnoi): mean difference = 237 (95% CI, 34 - 440), P-Value = 0.028 View more	-	01 Nov 2015
				Placebo
NCT01689337 (CTgov)	Phase 2	Knee Injuries	1	AS902330	mevamrpmmo = jmjzjmiwnu nbpddlwqsh (ltfxaqeuqc, nxjaqjczdr - dstjjckecu) View more	-	31 Aug 2015

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